Infection Management for Geriatrics in Long-Term Care Facilities

INFEC TION MANAGEMENT F O R G E R I AT R I C S I N L O N G -T E R M C A R E FA C I L I T I E S

EDITED

THOMAS

T.

BY

YOSHIKAWA

Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center Los Angeles, California

JOSEPH

G.

OUSLANDER

Emory University School of Medicine Atlanta, Georgia

Marcel Dekker, Inc.

New York • Basel

TM

Copyright © 2002 by Marcel Dekker, Inc. All Rights Reserved.

ISBN: 0-8247-0784-2 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright © 2002 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA

To our wives, Catherine Yoshikawa and Lynn Ouslander, for their love and support.

Preface

With the increasing growth of the aging population—especially those aged 85 years and older—over the next 40 years, there will be a parallel demand for longterm care. Such a demand is inevitable, given the changes, diseases, disabilities, and socioeconomic factors associated with growing old. When such age-related factors in an older person create a need for care, services, and support that cannot be met by family and other caregivers, the need arises for long-term care outside the home environment. Although there are different types and venues for longterm care, nursing homes (nursing facilities) remain the dominant sites for providing care for chronically and functionally disabled and cognitively impaired older persons. Thus, nursing homes serve as the prototype long-term care facility (LTCF) that manages chronically disabled elderly individuals. As more and more care is provided in LTCFs, inherent risks and problems arise when the population is very old, frail, and disabled. The population at risk resides in a closed institutional setting; the ratio of healthcare staff to residents may be suboptimal; and quick and easy access to diagnostic, therapeutic, and preventive interventions is limited. One of the most common risks (and complications) of long-term care is infection. Infection (or presence of a fever) is often the reason an LTCF resident is sent to an emergency department or transferred to an acute care facility. However, the clinical diagnosis of an infection in a frail, elderly LTCF resident may be quite difficult, given the atypical clinical manifestations of infection in the very old, limited availability of a clinician onsite in the LTCF to examine the resident, and lack of quick access to diagnostic laboratory and radiological tests. Moreover, once a presumptive diagnosis of infection is made, the decision for an appropriate therapeutic approach may be v

vi

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complex. Issues of advanced directives and/or desires of the resident/family regarding the extent of diagnostic and therapeutic interventions must be considered. Can the resident be treated in the LTCF or is transfer to an acute care facility more appropriate? Does the LTCF have the resources and appropriately trained personnel to treat the resident within the LTCF? If treatment is initiated in the LTCF, what antibiotics and dosages should be used? In addition, other clinical infectious disease issues to be considered when caring for residents in an LTCF include the following: What are the most common infections in this setting? What is the role of an LTCF nurse in managing infections? What ethical factors need to be considered? What should be done when an outbreak of an infection occurs? Are there drug-resistant pathogens in this setting, and how should these be managed? Infection Management for Geriatrics in Long-Term Care Facilities addresses these and many other important questions and issues related to the diagnosis, treatment, prevention, and control of infections in elderly residents of LTCFs. The book was written by internationally and nationally recognized experts in the area of infections, geriatrics, and long-term care. The editors are clinicians who have a long record of patient care, education and training, and research in the fields of geriatrics, gerontology, and long-term care. They are editor-inchief and deputy editor, respectively, of the Journal of the American Geriatrics Society, the leading journal in the field of aging. The book is divided into three major sections. The first is devoted to the principles of aging, long-term care, and infection, with chapters discussing the demographics of long-term care; the differences between acute care and long-term care; epidemiology and special aspects of infections in long-term care; host resistance changes with aging; the interrelationship between aging, nutrition, and immunity; altered clinical manifestations of infections with aging; ethical considerations in managing infections in this setting; the role of nursing in managing infections in LTCFs; principles of infection control in an LTCF; identification and management of outbreaks in an LTCF; and a rational approach to using antibiotics in residents of LTCFs. The second section focuses on the most common and important infectious diseases problems encountered in LTCFs. These include urinary tract infection; influenza and other respiratory viruses; pneumonia and bronchitis; tuberculosis; selected skin infections, i.e., herpes zoster, cellulitis, and scabies; infectious diarrhea; viral hepatitis; and vaccination. The third and final section addresses the problem of emerging drug-resistant pathogens in LTCFs, with detailed information on pathogenetic and molecular mechanisms for antibiotic resistance; methicillin-resistant Staphylococcus aureus; glycopeptide (primarily vancomycin)-resistant enterococci; gram-negative bacteria; and selected fungi (e.g., Candida). An appendix is included with definitions of common infections in a long-term care setting and guidelines for the evaluation of fever and infections in long-term care facilities.

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vii

The book is formatted for easy and quick access to key information; there are numerous figures and tables that summarize important data; and the most relevant and up-to-date references are provided. Clinicians will find this book informative, easy to read, and helpful in managing their LTCF residents with fever and infection. Infection Management for Geriatrics in Long-Term Care Facilities is an essential resource for all healthcare providers and administrators involved with the care of elderly residents in LTCFs. The editors would like to thank Ms. Patricia Thompson for retyping and preparing all the manuscripts in their final form. Thomas T. Yoshikawa Joseph G. Ouslander

Contents

Preface Contributors

v xiii

I.

Principles of Aging, Long-Term Care, and Infection

1.

Demographics and Economics of Long-Term Care A. Jefferson Lesesne and Joseph G. Ouslander

2.

Evaluation of Infections in Long-Term Care Facilities Versus Acute Care Hospitals Andrew D. Weinberg

15

3.

Epidemiology and Special Aspects of Infectious Diseases in Aging Thomas T. Yoshikawa

27

4.

Impact of Age and Chronic Illness-Related Immune Dysfunction on Risk of Infections Steven C. Castle

33

5.

Nutrition and Infection Kevin P. High

51

6.

Clinical Manifestations of Infections Dean C. Norman

71

7.

Ethical Issues of Infectious Disease Interventions Elizabeth L. Cobbs

79

1

ix

x

Contents

8.

Nursing Management of Infections Donna L. Barton and Janet D. Register

99

9.

Establishing an Infection Control Program Janet Nau Franck, Elizabeth Owens Schwab, and David W. Bentley

115

10.

Epidemiologic Investigation of Infectious Disease Outbreaks Chesley L. Richards, Jr., and William R. Jarvis

133

11.

An Approach to Antimicrobial Therapy Shobita Rajagopalan, Jay P. Rho, and Thomas T. Yoshikawa

155

II.

Special Infectious Disease Problems

12.

Urinary Tract Infection Lindsay E. Nicolle

173

13.

Influenza and Other Respiratory Viruses Ghinwa Dumyati and Ann R. Falsey

197

14.

Pneumonia and Bronchitis Joseph M. Mylotte

223

15.

Tuberculosis Shobita Rajagopalan

245

16.

Infected Pressure Ulcers Nigel Livesley and Anthony W. Chow

257

17.

Herpes Zoster, Cellulitis, and Scabies Kenneth Schmader and Jack Twersky

283

18.

Infectious Diarrhea Abbasi J. Akhtar

305

19.

Hepatitis Darrell W. Harrington and Peter V. Barrett

313

20.

Vaccinations Stefan Gravenstein

337

III. Emerging and Drug-Resistant Pathogens 21.

Pathogenesis and Molecular Mechanisms of Antibiotic Resistance Robert A. Bonomo

363

Contents

xi

22.

Methicillin-Resistant Staphylococcus aureus Larry J. Strausbaugh

383

23.

Vancomycin (Glycopeptide)-Resistant Enterococci Lona Mody, Shelly A. McNeil, and Suzanne F. Bradley

411

24.

Gram-Negative Bacteria Vinod K. Dhawan

429

25. Candida and Other Fungi Carol A. Kauffman and Sara A. Hedderwick Appendix A: Definitions of Common Infections in Long-Term Care Facilities Appendix B: Guide to Evaluating Fever and Infection in a Long-Term Care Setting Index

449

473 477 481

Contributors

Abbasi J. Akhtar, M.D., M.R.C.P. Department of Internal Medicine, Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California Peter V. Barrett, M.D. Department of Medicine, Harbor–UCLA Medical Center, Torrance, California Donna L. Barton, R.N., B.C., B.S.N., FACDONA/LTC Director of Nursing, Lake Eustis Care Center, Eustis, Florida David W. Bentley, M.D. Department of Internal Medicine, Saint Louis University School of Medicine, and Geriatric Research, Education, and Clinical Center, St. Louis VA Medical Center, St. Louis, Missouri Robert A. Bonomo, M.D. Department of Medicine, Case Western Reserve University, Cleveland, Ohio Suzanne F. Bradley, M.D. Department of Internal Medicine, University of Michigan, and Divisions of Geriatric Medicine and Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan Steven C. Castle, M.D. Geriatric Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, and UCLA School of Medicine, Los Angeles, California xiii

xiv

Contributors

Anthony W. Chow, M.D., F.R.C.P.(C), F.A.C.P. Department of Medicine, University of British Columbia, and Division of Infectious Diseases, Vancouver Hospital Health Sciences Centre, Vancouver, British Columbia, Canada Elizabeth L. Cobbs, M.D. Department of Geriatrics and Extended Care, Washington D.C. VA Medical Center, and George Washington University, Washington, D.C. Vinod K. Dhawan, M.D., F.A.C.P., F.R.C.P.(C) Department of Medicine, Charles R. Drew University of Medicine and Science, and UCLA School of Medicine, Los Angeles, California Ghinwa Dumyati, M.D. Infectious Disease Unit, University of Rochester School of Medicine, and Rochester General Hospital, Rochester, New York Ann R. Falsey, M.D. Infectious Disease Unit, University of Rochester School of Medicine, and Rochester General Hospital, Rochester, New York Janet Nau Franck, R.N., M.B.A., C.I.C. Consulting Professionals, Inc., St. Louis, Missouri Stefan Gravenstein, M.D., M.P.H. Department of Medicine, Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, Norfolk, Virginia Darrell W. Harrington, M.D. Department of Medicine, Harbor–UCLA Medical Center, Torrance, California Sara A. Hedderwick, M.R.C.P., D.T.M.&H Department of Infectious Diseases, Royal Victoria Hospital, Belfast, Northern Ireland Kevin P. High, M.D., M.Sc. Sections of Infectious Diseases and Hematology/Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina William R. Jarvis, M.D. Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia Carol A. Kauffman, M.D. Department of Internal Medicine, University of Michigan, and Division of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan A. Jefferson Lesesne, M.D. Geriatric Medicine and Gerontology, Emory University School of Medicine, Atlanta, Georgia

Contributors

xv

Nigel Livesley, M.D., F.R.C.P.(C) Department of Medicine, University of British Columbia, and Division of Infectious Diseases, Vancouver Hospital Health Sciences Centre, Vancouver, British Columbia, Canada Shelly A. McNeil, M.D., F.R.C.P.(C) Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada Lona Mody, M.D. Department of Internal Medicine, University of Michigan, and Division of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan Joseph M. Mylotte, M.D. Department of Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York Lindsay E. Nicolle, M.D., F.R.C.P.(C) Department of Internal Medicine, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada Dean C. Norman, M.D. Chief of Staff, VA Greater Los Angeles Healthcare System, and UCLA School of Medicine, Los Angeles, California Joseph G. Ouslander, M.D. Department of Medicine, Emory University School of Medicine, Atlanta, Georgia Shobita Rajagopalan, M.D. Department of Internal Medicine, Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California Janet D. Register, B.S., ICP, R.N., B.S.N. Department of Infection Control, Leesburg Regional Medical Center, Leesburg, Florida Jay P. Rho, Pharm.D. Department of Pharmaceutical Sciences, University of Southern California University Hospital, Los Angeles, California Chesley L. Richards, Jr., M.D. Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia Kenneth Schmader, M.D. Department of Medicine, Duke University Medical Center, and Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, North Carolina Elizabeth Owens Schwab, R.N., B.S.N., M.P.H. Center for Healthcare Quality, BJC Health System, St. Louis, Missouri

xvi

Contributors

Larry J. Strausbaugh, M.D. Division of Hospital and Specialty Medicine, Portland VA Medical Center, and Department of Internal Medicine, Oregon Health Sciences University School of Medicine, Portland, Oregon Jack Twersky, M.D. Department of Medicine, Duke University Medical Center, and Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, North Carolina Andrew D. Weinberg, M.D., F.A.C.P. Department of Medicine, Emory University School of Medicine, Atlanta, Georgia Thomas T. Yoshikawa, M.D. Department of Internal Medicine, Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California

1 Demographics and Economics of Long-Term Care A. Jefferson Lesesne and Joseph G. Ouslander Emory University School of Medicine, Atlanta, Georgia

I. INTRODUCTION Long-term care has been defined as “a set of health, personal care, and social services delivered over a sustained period of time to persons who have lost or never acquired some degree of functional capacity” (1). Long-term care includes a broad range of services for chronically disabled individuals over an extended period. Venues for care are predominantly nursing homes (nursing facilities), assisted living facilities, senior housing, and personal dwellings without much, if any, coordination among these sites. The nursing facility remains the most common institutional setting for long-term care. In 1996 there were approximately 16,500 certified facilities with 1.8 million beds (2). This is nearly three times the number of acute care hospitals and twice the number of hospital beds. An aging society will create ever-increasing demands for services and costs associated with longterm care. This chapter will review the relevant demographic and economic factors affecting nursing facilities, with a brief discussion of the assisted living facility market.

II. DEMAND FOR NURSING FACILITY CARE Three main factors contribute to the demand for nursing home care: (1) the number of frail older adults with physical functional disabilities, mental health problems, or both that preclude independent living or community-based care; (2) the available social support system; (3) available, accessible and affordable commu1

2

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Table 1 Factors Affecting the Need for Nursing Home Admission Characteristics of the individual Age, sex, race Marital status Living arrangements Degree of mobility Ability to perform basic and instrumental activities of daily living Urinary incontinence Behavior problems Mental status Memory impairment Mood disturbance Tendency for falls Clinical prognosis Income Payment eligibility Need for special services Characteristics of the support system Family capability Health and function of spouse (if married) Presence of responsible relative (usually adult child) Family structure of responsible relative Employment status of responsible relative Physician availability Amount of care currently received from family and others Community resources Formal community resources (See Table 2) Informal support systems Presence of long-term care institutions Characteristics of long-term care institutions Source: Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 3rd ed. New York, McGraw-Hill, 1994.

nity-based long-term care resources (Table 1). 57% of people aged 65 and older report long-term care needs as measured by their need for assistance with activities of daily living (ADLs). Among those aged 85 and older, 21% resided in nursing facilities in 1995. In 1996, the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality) concluded in a consensus panel that moderate to severe dementia was prevalent in 2% of those aged 65 to 69, 4% of those aged 70 to 74, 8% of those aged 75 to 79, and 16% of those older than aged 85 (3). Another study concluded that 47% of people older than aged 85

Demographics and Economics

3

had some degree of dementia (4). Figure 1 depicts the projected increase in those with dementia over the next 50 years. The older, more cognitively impaired individual is more likely to need assistance with ADLs and, therefore, will need some form of long-term care. Much of the long-term care in the United States is carried out by family and friends, especially wives and daughters. A survey of informal caregivers indicated that nearly 75% are women, whereas 40% are spouses, and 35% are adult children (5). The average age of the informal caregiver is 60, with 70% of them not working outside the home. Two-thirds of those who work outside the home reported conflicts with work and caregiving. Approximately 20% of men and 50% of women aged 75 and older live alone. About one-third of those who live alone have no children. The older population now tends to have fewer children and are more geographically disbursed than previous generations (Fig. 2). The significance of informal caregiving is evident by the fact that 50% of older adults with long-term care needs and no family support reside in nursing facilities, compared with 7% of those with family caregivers (6). The geriatric population will see unprecedented growth with the aging of the baby boomer generation, and this growth will greatly increase the likelihood of needing long-term care (Fig. 3). The number of Americans aged 65 and older is expected to increase by approximately 60 to 90 million by 2040. The 85 and older population—those most likely to need long-term care—will increase by 8 to 20

Figure 1 Projected number of persons with dementia in the U.S. population. (Based on prevalence estimates and projections from the National Institute on Aging and U.S. Bureau of the Census.)

4

Lesesne and Ouslander

Figure 2 Frequency of seeing children among community-dwelling elderly who live alone. (Courtesy of Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 2nd ed. New York, McGraw-Hill, 1989.)

Figure 3 Actual and projected growth of the U.S. geriatric population. (Courtesy of Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 3rd ed. New York, McGraw-Hill, 1994.)

Demographics and Economics

5

Black Female White Female Black Male White Male

At Age

85

75

65 0

5

10 Years Remaining

15

20

Figure 4 Life expectancy in the geriatric population. (Courtesy of Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 2nd ed. New York, McGraw-Hill, 1989.)

million people by this date (7). A portion of the increase is the result of increased life expectancy. Men aged 65 could expect to live 15 years in 1995; by 2030, they can expect to live 18 years (Fig. 4). Some estimates project the number of people aged 65 and older with functional limitations to be approximately 20 to 30 million by 2040. These demographic shifts will substantially increase the need for nursing facility care. Many community services are available to frail older adults. These services may delay or prevent nursing facility admission for some people (Table 2). They tend to be fragmented and, in many cases, are not reimbursable by most insurance or governmental funding sources. Additionally, there is poor integration of care in the acute and long-term care settings. The primary funding sources of Medicare and Medicaid have differing eligibility requirements and coverage rules that prevent integration. There is also a fear of financial loss on the part of commercial carriers, as there is no risk adjustment for chronically ill or disabled people. Social health maintenance organizations attempt to add community services and short-term nursing home care to a traditional health maintenance organization health plan. The Program for All-Inclusive Care for the Elderly (PACE) is designed for frail older adults, eligible for Medicaid, who are nursing home certifiable. PACE attempts to help these individuals age in the community. Many states are also developing their own initiatives to provide better community care and delay nursing home admission. The number of such programs is increasing, but many frail elders will reach a point at which institutional care is the most appropriate alternative. The growth in the number of assisted living facilities has had an impact on long-term care. There is no clear definition of what constitutes an assisted living

6

Lesesne and Ouslander

facility; however, these venues provide some level of long-term care for their residents. A national study of assisted living facilities recently estimated that there were approximately 11,500 facilities with 650,000 beds providing services to 560,000 residents (8). This survey included facilities with at least 11 beds, providing 24-hour oversight and serving at least two meals per day. The major difference is that this industry is composed of more real estate developers and hotel managers than healthcare providers. Nursing home usage rates vary by age, sex, and race (Fig. 5). There are more whites than blacks and more women than men in nursing facilities. Nearly 25% of white women reside in a nursing home by age 85. Interestingly the number aged 65 and older who stay overnight in a nursing home fell by 8% from 1985 to 1995

Table 2 Example of Formal Community Services Available Outside of Nursing Homes Housing Senior apartments Residential care facilities Assisted living Foster care Life care community Health promotion activities Wellness programs Exercise classes Family and patient education Nutrition consultation Meal programs Volunteer programs Outreach Screening clinics Mobile vans Discharge planning Case management Information and referral Meals-on-Wheels Transportation Emergency response system Respite care

Outpatient centers Geriatric clinics Psychosocial counseling Rehabilitation Adult day care Day hospital Home health Home health agencies Medicare-certified Private Visiting nurse association Hospice Homemaker Chore Home infusion therapies Durable medical equipment Acute inpatient units Geriatric Rehabilitation Psychiatric Alcohol/substance abuse

Source: Ouslander JG., Osterweil D, Morley J. Medical Care in the Nursing Home, 2nd ed. New York, McGraw-Hill, 1997.

Demographics and Economics

7

Figure 5 Percent of population aged 65 and older in nursing homes by age, sex, and race. (Based on 1985 data from the National Center for Health Statistics.)

(9). This decline may have resulted from a decline in disability rates of the elderly, increased use of home health services, and the growth in assisted living facilities. All of these tend to delay or prevent placement in a nursing facility.

III. ECONOMICS OF LONG-TERM CARE Financing for long-term care in the United States is primarily provided through private funding and governmental assistance programs, including Medicare and Medicaid. Private funding can include personal resources and may include a component of long-term care insurance. There are also “Medigap” insurance policies to cover the copayment required by Medicare. Long-term care costs as a percentage of personal health care expenditures have increased from 4% in 1960 to 11% in 1993 (3). Approximately $106 billion was spent on long-term care, including home care, in 1995. Medicare accounted for nearly 18% and Medicaid 38% (21% state Medicaid and 17% federal Medicaid) (Fig. 6). States are the major financiers of long-term care for older adults, whereas the federal government finances most acute care. Many Americans are unprepared for long-term care expenditures because they believe it is a Medicare benefit.

8

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Figure 6 Expenditures on nursing home and home health care by source of funds, 1995. (From Health Care Financing Administration. Cited by National Academy on Aging, 1997.)

A. Medicare Medicare is a governmental insurance program that covers the cost of acute hospitalization for those aged 65 and older, as well as some disabled individuals younger than age 65 and those requiring renal dialysis or transplant. In addition, it covers outpatient services and post-acute hospital care for up to 100 days after a 3-day hospitalization. Currently there are approximately 39 million beneficiaries and in 1997, the annual budget was $215 billion dollars. Sixty-nine percent of Medicare expenditures goes to hospitals, with another 25% covering physician services. Less than 5% goes to nursing home care. Medicare expenditures for home health increased nearly 10 times from 1987 to 1995 (10). In response, Congress and the President enacted the 1997 Balanced Budget Act that greatly reduced these payments and initiated a significant effort to reduce fraud and abuse. Many states have developed strategies to help their Medicaid recipients maximize their Medicare home health benefits in an effort to conserve state Medicaid dollars. Medicare also limits its funding for long-term

Demographics and Economics

9

care by only covering post-acute or “subacute” skilled care. Medicare provides post-acute skilled care for 100 days after an acute hospitalization of 3 or more days. To qualify, the patient must require daily skilled nursing care or rehabilitation services for the condition that was treated in the hospital (Table 3). Funding for post-acute care from Medicare is transitioning to a prospective payment system (PPS) based on resident problems identified in the Minimum Data Set (MDS). Under the PPS model, a capitated reimbursement is made to the nursing home for care of particular medical problems after an acute hospitalization. The reimbursement is calculated based on the MDS and then translated into resource utilization groups or “RUGS,” similar to the Medicare diagnostic related group (DRG) payment system for acute hospitals. An important component is that all ancillary services (rehabilitation therapy, laboratory services, medications, etc.) are now bundled into one payment. This has profound implications for the relationship between nursing homes and physicians, because under PPS the nursing home bears the cost of physician-ordered laboratory tests, medications and therapies. B. Medicaid Medicaid is a federally sponsored, state-administered program to provide health insurance for the indigent. It covers both acute hospital care and outpatient services for those who qualify based on means testing. The long-term care compo-

Table 3 Admission Criteria to Subacute Units Intravenous antibiotics Physical therapy six to seven times/week Occupational therapy five times/week Weaning oxygen with blood gas measurements three times/week Tracheal suctioning at least two times/shift Respiratory therapy treatment three times/day or more frequently Capillary blood glucose monitoring two times/day with insulin coverage Injectable medications every 8 hours or two times/day Wound care (sterile) day Tube feeding Laboratory test monitoring every 2 to 3 days Renal dialysis with monitoring Bladder training Pain management (parenteral) Skilled nursing observation of congestive heart, liver, or renal failure Physician visits at least weekly

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nent of Medicaid covers nursing home care on a means-tested basis. This program insures 41 million people (10% elderly) at an annual cost of $160 billion. Sixtynine percent of expenditures go to nursing homes, with 17% to hospitals and 3% to physician services. Each state administers the program differently, so there is substantial variability is terms of benefits covered. Virtually all nursing home care is paid for out-of-pocket or by Medicaid, which has led to a phenomenon known as “spend down” (Figs. 7 and 8). Individuals and families will deplete a person’s assets until they can pass the means test

Figure 7 Top: Sources of overall health care expenditures for the geriatric population. Bottom: Per capita health care expenditures by type of care and source for the geriatric population. Based on 1984 data. (Courtesy of Kane RL, Ouslander JG, Abrass IB, Essentials of Clinical Geriatrics, 2nd ed. New York, McGraw-Hill, 1989.)

Demographics and Economics

11

Figure 8 Proportions of Medicare, Medicaid, and out-of-pocket expenditures used for different types of care by the geriatric population. Based on data from the United States Special Committee on Aging, 1986. (From Ref. 1.)

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for Medicaid funding for long-term care. Since nursing home care can cost as much as $40,000 to $60,000 per year, it does not take older adults very long to qualify for Medicaid. As a result, Medicaid has become, in effect, the payer of last resort for institutional long-term care. This has inspired many state Medicaid agencies to develop and work with programs that prevent or delay the need for institutional care. C. Private Funding Private long-term care insurance only covered 6% of nursing home and home-care costs in 1995 (6). The number of policies sold has recently seen a dramatic increase from 800,000 in 1987 to nearly 5 million in 1996. A wide range of coverage is available through these policies; however, most provide some type of home care component to avoid or delay nursing home coverage. Several states have promoted the purchase of long-term care insurance by providing a mechanism to protect assets from Medicaid eligibility requirements equal to the amount of longterm care coverage.

IV. EVOLVING CHANGES IN LONG-TERM CARE The long-term care industry has seen substantial growth of post-acute care in the United States over the last decade. As the population ages and hospital lengths of stay are shortened, more medically complex patients with greater nursing home care needs are being discharged from hospitals to nursing facilities. Often they are not functionally able or medically stable enough to return home. Subacute units in nursing facilities have become the place for residents to convalesce before their ultimate discharge. For these units to succeed, there needs to be adequate reimbursement, availability of skilled nurses, and quality medical care, as well as adequate ancillary services. Regulations to set standards for staffing ratios would most likely improve quality of care in nursing homes (11). Nursing homes would also benefit from a survey process that provides education and is outcomes based, rather than a punitive process to identify misconduct. Additionally, unfunded government mandates are difficult to implement, and they drain resources. Improved reimbursement will help ensure adequate staffing of nurses and therapists, as well as improve the availability of ancillary services. Improving nursing education and professional opportunities will also assist in attracting and retaining quality staff. This is true for physicians, nurse practitioners, and physician assistants. Innovative programs are essential to improving job satisfaction and quality of care provided by nursing aides, since they provide more than 90% of hands-on care in nursing homes.

Demographics and Economics

13

Reimbursements that are adjusted for risk and complexity will help provide quality care in the most appropriate setting. The RUGs system is a step in this direction. Outcome monitoring based on quality indicators will also provide the appropriate incentives for quality care in the nursing home (12). Integrated care systems composed of hospitals, primary care providers, long-term care facilities, and community-based partners will also improve quality and have financial implications. These systems must have shared visions, goals, and financial incentives to provide good care. They also implement care standards as well as develop much needed information systems. All of these features will reduce practice variability and medical errors, and improve the quality of care.

REFERENCES 1. 2. 3.

4.

5. 6. 7.

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9. 10. 11.

12.

Kane RA, Kane RL. Long-Term Care: Principles, Programs, and Policies. New York, Springer, 1987. American Association of Retired Persons: Across the States 1998. Profiles of LongTerm Care Systems, 3rd ed. Washington, DC, 1998. Stone RI. Long-Term Care for the Elderly with Disabilities: Current Policy, Emerging Trends, and Implications for the Twenty-First Century. Milbank Memorial Fund, 2000. Costa PT, Williams TF, Albert MS. Recognition and Initial Assessment of Alzheimer’s Disease and Related Dementias. Clinical Practice Guideline No. 19, AHCPR Publication No. 97–0702. Washington, DC, Agency for Health Care Policy and Research, 1996. The Assistant Secretary for Planning and Evaluation and the Administration on Aging: Informal Caregiving. Compassion in Action. Washington, DC, 1998. National Academy on Aging. Facts on Long-Term Care. Washington, DC, 1997. Available at http://geron.org/NAA/ltc.html U.S. Bureau of the Census. Population Projections of the United States by Age, Sex, Race, and Hispanic Origin: 1995 to 2050: Current Population Reports, P25–1130. Washington, DC, U.S. Government Printing Office, 1996. Hawes C, Rose M, Phillips CD, Iannacchione V. A National Study of Assisted Living for the Frail Elderly: Results of a National Telephone Survey of Facilities. Beachwood, Ohio, Menorah Park Center for the Aging, 1999. Bishop CE. Where are the missing elders? The decline in nursing home use, 1985 and 1995. Health Affairs 1999; 18(4):146–155. Kenney G, Rajan S, Soscia S. State spending for Medicare and Medicaid home care programs. Health Affairs 1998; 17(1):201–212. Wunderlich GS, Kohler PO (eds). Improving the Quality of Long-Term Care: A Report of the Institute of Medicine. Washington, DC, National Academy Press, 2001. National Academy of Sciences. Zimmerman DR, Karon SL, Arling G. Development and testing of nursing home quality indicators. Health Care Financing Rev 1995; 16:107–127.

2 Evaluation of Infections in Long-Term Care Facilities Versus Acute Care Hospitals Andrew D. Weinberg Emory University School of Medicine, Atlanta, Georgia

I. LONG-TERM CARE FACILITY VERSUS ACUTE CARE HOSPITAL In general, evaluation and management of acute care infections remains one of the greatest challenges to staff and healthcare practitioners in institutional long-term care facilities (LTCFs). The general goals and objectives, staffing patterns, available resources for diagnostic testing, and primary role of physicians and nursing staff are different between an acute care hospital and an LTCF, as indicated in Table 1. Thus, the approach to evaluating infections in LTCFs will also be different between an acute care hospital and an LTCF. The differences in the evaluation of infections in the hospital setting include the infrequent presence of physicians in the LTCFs, the inability to obtain timely and accurate laboratory and radiological data, and the limited nursing assessment that occurs at the LTCF, which is subsequently transmitted to the healthcare practitioner via telephone.

II. HOW INSTITUTIONAL LTCFS DIFFER IN INFECTION EVALUATION A. Staffing and Resources The majority of care in an LTCF is provided by licensed nursing staff (licensed practical nurses [LPNs] and registered nurses [RNs]). The staffing ratios in facil15

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Weinberg

Table 1 Differences Between Acute Care Facility and Long-Term Care Facility Parameter Patient population Setting Goals Length of stay Physician role Infection definition Resources for infection control Isolation capability

Acute care facility

Long-term care facility

Young and old High technology Acute disease treatment Days, weeks Primary Clinical
tests Broad

Predominantly old Home-like Comfort, support Months, years Secondary, limited Clinical
limited tests Variable and often limited

Broad

Limited to none

Adapted from: Yoshikawa TT, Norman DC: Infection control in long-term care. Clin Geriatr Med 1995;11:467–480.

ities may range from one licensed nurse per 20 residents to as high as one to 40 residents, depending on the shift. Certified nursing assistants (CNAs) provide the majority of hands-on care, including grooming, washing, ambulation, feeding, dressing, and overall supervision. The CNA staffing ratios may range from one CNA per 8 to 15 residents, again depending on the particular shift. In the majority of LTCFs, physicians are physically present in the facility for a limited number of hours per week and are only required by state or federal regulations to visit, on average, every 30 to 60 days after the first 90 days of residency in the facility. Thus, the vast majority of changes in a resident’s baseline condition and responses to acute medical illnesses are managed by telephone or fax transmissions from the RN to LPN to the primary or cross-covering physician of record, a nurse practitioner (NP), or a physician assistant (PA) (1–3). Often limited technical resources are available for the evaluation of infections in the LTCF setting, especially on evenings, nights, weekends, and holiday shifts. Practice guidelines for the evaluation of fever and infection in the long-term care setting have been recently published (4), but the majority of triage for an acute illness is done by telephone exchange with the nursing staff, often without the benefit of laboratory data at the time of the first contact. The availability of specialty consultations is virtually nonexistent onsite. Referrals to infectious disease specialists outside the nursing facility are difficult to arrange and involve significant nonreimbursable transportation costs. In general, staff and healthcare practitioners rely on the clinical history and symptoms and signs of illness rather than on advanced diagnostic testing. The CNAs are the first line of detection, as they interact closely with the residents and customarily can detect small changes in mental status or functional decline that could signal an underlying infection. The CNAs then report these observations to the licensed nurse on duty. The nurse is then expected to obtain vital signs and per-

Long-Term Care and Acute Care Facilities

17

form a nursing assessment so that this information, along with any recent, pertinent history, can be given to the practitioner when he or she is contacted. Infection remains one of the most common causes of death among LTCF residents and a frequent reason for transfer to the acute care setting and subsequent hospitalization (5–7). Those LTCF residents who are at greatest risk for developing clinical infections are more likely to require higher levels of nursing care, have significant functional disability, or have more indwelling catheters (3,8). Infections of the urinary tract, pulmonary system, and skin remain the most common sites of infection in the LTCF setting. B. Recognition of Infection Recognition of infection in this population may be hindered by the atypical presentation of these illnesses in cognitively impaired individuals who may not be able to effectively communicate to their caregivers when they feel ill (9,10). Certified nursing assistants or licensed nursing staff may be able to detect infections by subtle declines in cognitive or physical functioning or by the presence of new or increasing confusion. One of the universal indicators of infection is the presence of fever. However, it is now known that the basal body temperatures in the frail older adult may be lower than the well-established mean value of 37°C or 98.6°F (11). Thus, fever as a marker for infection in the LTCF resident is not the most sensitive of indicators. Also, “fever” can be defined somewhat differently from facility to facility, so it is important to be aware of the current definition used in each facility, especially when implementing evaluation and treatment protocols for infection. Additionally, temperatures may be obtained from different sites of measurement, including oral, rectal, axillary, or tympanic, and all are not necessarily equally as accurate (12). (See also Chapter 6, Clinical Manifestations of Infections.) The routine use of acetaminophen can mask the presence of fever, and its routine use should be discouraged until the source of fever is identified or the evaluation of an infection is in progress (13). Once the presence of a new fever is documented, the source of this temperature elevation should be sought. The particular areas to assess for potential sources of infection include the oropharynx, conjunctiva, skin (whole body evaluation), chest, heart, abdomen, perineum, perirectal area, and the central nervous system (14). Several groups have outlined general guidelines for the evaluation of suspected infections; however, these recommendations represent a consensus of opinion of individuals representing various longterm care organizations involved but have not been validated to date (15–17). Concurrent dehydration can also pose a risk to the outcome of infections in this population. In one study of 40 febrile LTCF residents (5), 24 (60%) had evidence of hypernatremia, increased blood urea nitrogen to serum creatinine ratio, or both. Studies have shown that not one specific physical finding was deemed to

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Weinberg

be of any particular value in diagnosing dehydration (5,18), and that laboratory data remain the most objective and easily attainable information on the state of hydration. C. The Initial Evaluation of Suspected Infection The initial assessment is usually completed by the nurse on duty in the facility after being notified of a change in status by the CNA. The nurse then reports the findings via telephone to the NP, PA, or attending physician (4). (See Appendix B for a summary of guidelines for evaluation of fever and infection in LTCF [4]) The NP, PA, or physician may then order additional laboratory or radiological tests, initiate treatment, or order the resident transferred to an acute care setting for further evaluation. Initial laboratory data obtained usually consists of a urinalysis with culture if an infection in the genitourinary tract is suspected, a chest X-ray if a pulmonary process is suspected, and a complete blood count with differential to determine the severity of the problem (Fig. 1). “Stat” laboratory and radiological tests are available, but several hours or even a full day may elapse until the results are relayed back to the ordering healthcare practitioner. If an epidemic is suspected in the facility (usually defined as 10% or more of the resident population ill at the same time), nursing staff should alert the director of nursing who, in turn, must notify the medical director. The infection control nurse should also be contacted so that ongoing monitoring can be carried out. Nursing staff should be briefed or inserviced (as time permits) on the relevant portions of the infection control policies for the facility that would pertain to this outbreak. Overall evaluation and treatment in the LTCF setting must take into consideration the resident’s wishes (or a legal guardian or next of kin if the resident is incompetent to make medical decisions), the cost of evaluation, and the effect of treatment on the quality of life given the wishes of the resident/family. Tests should be ordered if the results will cause the clinician to change or reassess the current treatment and improve overall management or the comfort of the resident. The need for specific laboratory tests should be based on the clinical presentation of each resident. Protocols to aid the staff in their approach to suspected infections should be developed and distributed, and inservice education should be provided to all three shifts. The ability to obtain adequate culture specimens may be problematic in the LTCF setting. The prevalence of asymptomatic bacteriuria may run as high as 50% of all noncatheterized female residents of LTCFs and does not usually require treatment with antibiotics (19). This may confound the interpretation of culture results. When such cultures are indicated, it is possible to collect adequate specimens in both men and women without catherization (4). Blood and sputum cultures are extremely difficult to obtain in the LTCF setting. Obtaining adequate

Long-Term Care and Acute Care Facilities

19

Suspected Infection Functional decline Change in mental status Fever Onset of viral, urinary tract, respiratory or diarrheal symptoms Evidence of unexplained discomfort (crying, moaning, agitation) Significant decrease in food/fluid intake Nurse/Certified nursing assistant obtains vital signs (Temperature, pulse, respiratory rate, and blood pressure) Perform nursing assessment Review chart and document all assessments Call practitioner to relay information and recent medical history Note any current advance directives Practitioner

assesses

stability

via

telephone

or

by

visit

Unstable Advance directive limits intervention

Unstable No advance directive

Stable

Call family Comfort measures

Call family Transfer to acute care facility

Call family Order laboratory or other tests Order treatment if clinically indicated

Follow-up with family

Follow-up with family

Follow-up with family

Document in chart rationale and goals

Document in chart rationale and goals for transfer

Document all medical orders and test results Adjust treatment as indicated

Establish Continuous Quality Improvement (CQI) process for ongoing review and analysis of cases when resident is transferred to an acute care facility

Figure 1 Recommended clinical evaluation for suspected infections in long-term care residents.

specimens for sputum cultures in the LTCF setting is made difficult by the technical difficulties associated with the procedure in frail, cognitively impaired residents and the lack of specific training on the part of the staff. Additionally, contracted laboratories rarely can provide this service to LTCFs. Blood cultures obtained within 24 hours of presentation have been associated with improved sur-

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vival in community-acquired pneumonias with sepsis (20), but there are no similar studies in the LTCF setting and thus are not generally recommended (4). Pulse oximetry can be useful in assessing arterial oxygen partial pressures and is relatively inexpensive and easy to use in the LTCF setting. It can be a predictor of impending respiratory failure requiring hospital admission (21). Assessment of the resident for impending respiratory failure can also be done at the bedside using a rate greater than 25 breaths per minute and confirmed by pulse oximetry indicating an oxygen saturation of less than 90%, as suggested in the recent modification of the Pneumonia Prognosis Index in nursing home residents (22). Because respiratory therapy services are generally not available in LTCFs, pulse oximetry measurements by nursing staff can be very helpful in treating residents suspected of having pneumonia. D. Subacute Care Infection Control There are few articles in the literature regarding infection control practices in subacute (postacute care; PAC) units (23), and there is no mention of PAC units as a special setting in either the position paper on infection prevention and control in LTCFs from the Association for Professionals in Infection Control and Epidemiology or the Society for Healthcare Epidemiology of America (24). Postacute Care units are a specified number of Medicare-certified beds within an LTCF designed to provide more advanced medical, nursing, and rehabilitative services to post-hospitalized older adults for a period not exceeding 100 days per calendar year under Medicare Part A. The ability to administer intravenous antibiotics is a commonly provided service (25). Many individual patients are admitted to PAC units for completion of antimicrobial therapy for already diagnosed and partially treated infections, such as chronic osteomyelitis or endocarditis. Some deconditioned patients in these units may develop pneumonia because of their overall poor medical condition or from aspiration (e.g., after a stroke). The subsequent antibiotic administration, which can be accomplished in most LTCFs with PAC units (25), will usually cover the majority of nosocomial infections one might expect to encounter. The LTCF facility medical director (or PAC unit medical director) can be involved in the screening of high-acuity patients with known infections before their acceptance into the unit (26). This allows the stability of the patient’s infection to be assessed, as well as anticipated equipment and medical needs (e.g., the presence of central lines, specialty mattresses, stage IV pressure ulcer management). There have been recent changes to reimbursement for subacute services in PAC units involving a prospective payment system (PPS); a fixed per diem reimbursement to the facility based on functional and medical needs is provided. This PPS payment is required to cover all nursing and ancillary services, including the

Long-Term Care and Acute Care Facilities

21

cost of X-rays, laboratory tests, medications, and intravenous administration of antibiotics performed in the facility. As the evaluation and treatment of complicated infections that develop after admission to a PAC unit will be borne by the facility under PPS, it has the potential to affect the assessment or treatment of acute infections in this setting.

III. WHEN TO TRANSFER LTCF RESIDENTS TO AN ACUTE CARE SETTING An ongoing issue is appropriate use of the emergency department (ED) as a resource for the evaluation of suspected infections in LTCF residents. Some studies have suggested that such transfers are overutilized and deem them inappropriate (27,28). The expense and inconvenience to the resident is considerable when such transfers are not properly used. The reasons for and frequency of transfers of LTCF residents to EDs for evaluation vary considerably by practice and location (Table 2) (27,29). The ability to adequately evaluate, monitor, and safely treat an LTCF resident is often the key question confronting the practitioner. Also, the inability to obtain necessary radiological or laboratory testing, the nursing assessment of the resident’s stability, and family recommendation will all affect the practitioner’s final decision on whether to transfer an individual. Most common bacterial pathogens seen in the LTCF setting can be treated with broad-spectrum oral antimicrobial therapy (30,31), but some practitioners, for a variety of reasons Table 2 Reasons to Transfer an LTCF Resident to an Emergency Department for Suspected Infection in Absence of Advance Directives • Abrupt change in vital signs or mental status associated with suspected infection • Inability to maintain adequate hydration and nutrition • In nurse’s judgment, the resident is not stable and practitioner not able to make onsite evaluation • Infections that are not responding to initiated treatment • Need for intravenous antibiotics or other necessary treatment that cannot be administered at the facility • Inability to obtain critical laboratory or radiological studies in the LTCF setting in a timely manner • Required infection control measures cannot be adequately implemented in the facility • Family concerns that adequate care is not being provided in the facility and requests transfer for more aggressive intervention LTCF  Long-term care facility. A suggested algorithm for evaluation of a suspected infection in the LTCF is shown in Figure 1.

22

Weinberg

including potential legal liability, may routinely order the transfer of all “acutely” ill residents to the local ED for “evaluation.” The ideal solution for those frail LTCF residents whose benefit/risk ratio for transfer and potential hospitalization is low is to discuss these issues in advance with the individual or a legal representative and specify guidance to the practitioner in the form of an advance directive. However, use of advance directives before the onset of a crisis is relatively low. Advance directives requesting “comfort care only” or “do not hospitalize” may facilitate the management of the LTCF resident with a suspected infection. However, studies examining advance directives in regard to the evaluation of suspected infections do not exist. Antibiotic treatment appears to be provided less often to residents with urinary, respiratory, or skin infections who have advance directives specifying “comfort care only” (32). Developing and implementing protocols to ensure that LTCF nursing staff can obtain and communicate adequate baseline information and assessments of the resident is critical for the practitioner to proceed with an organized and logical evaluation of a potential infection. Because much, if not all, of the initial information is transferred from the facility to the practitioner by telephone, this step may be considered the critical ink in the flow of information. More complete protocols for effective communication between nurses and physicians regarding resident assessment have been published (33), and one is available by the American Medical Directors Association (34). Following the resident’s advance directives and consulting with the legal representative can certainly give the practitioner direction as to the desired degree of evaluation or intervention and whether transfer to an ED is appropriate. If transfer is not desired, then appropriate laboratory, radiological, or specimen collection can be ordered to complete the evaluation at the LTCF site. Follow-up on any ordered tests and the response to prescribed treatment must be an ongoing process between the facility and the practitioner. Any pending laboratory or radiological results or recent family decisions as to the desired intervention should be conveyed to the “on call” practitioner for the night or weekend to avoid confusion and unwanted or unnecessary interventions. Facilities should develop Continuous Quality Improvement projects to review the entire evaluation and transfer process of residents to monitor the efficacy of current policies and procedures. Information on transfers and hospital admissions should be collected to assess whether there are procedures that can be implemented or current policies modified to improve the efficiency of the system in use. The facility medical director should be involved in the development, implementation, and review of all protocols to assure efficiency of assessments and information control procedures in collaboration with the infection control nurse and director of nursing. Data should also be collected on antibiotic resistance patterns, if possible (35).

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23

IV. SUMMARY The evaluation and treatment of infections in LTCFs is significantly different from acute care hospitals in many ways, including the availability of onsite assessment by physicians, specialty consultants, and diagnostic technologies. Although the vast majority of the more common clinical infections and their manifestations can be diagnosed and treated in the LTCF setting, there are instances when the severity of the illness or the treatment required may necessitate transfer to an acute care facility. Keeping this in perspective, advance directives and family discussions should be used to avoid undesired hospital transfers or aggressive treatments whenever possible. The medical director should be extensively involved in the development, review, and implementation of all infection control and treatment protocols. REFERENCES 1. 2. 3. 4.

5.

6. 7.

8. 9. 10. 11.

12.

Evans JM, Chutka DS, Fleming KC, Tangalos EG, Vittone J, Heathman JH. Medical care of nursing home residents. Mayo Clin Proc 1995; 70:694–702. Ouslander JG, Osterweil D. Physician evaluation and management of nursing home residents. Ann Intern Med 1994; 121:584–592. Smith PW, Rusnak PG. Infection prevention and control in the long-term care facility. Infect Control Hosp Epidemiol 1997; 18:831–849. Bentley DW, Bradley S, High K, Schoenbaum S, Taler G, Yoshikawa TT. Practice guideline for the evaluation of fever and infection in long-term care facilities. J Am Geriatr Soc 2001; 49:210–222. Weinberg AD, Pals JK, Levesque PG, Beal LF, Cunningham TJ, Minaker KL. Dehydration and death during febrile episodes in the nursing home. J Am Geriatr Soc 1994; 42:968–971. Irvine PW, Van Buren N, Crossley K. Causes for hospitalization of nursing home residents: The role of infection. J Am Geriatr Soc 1984; 32:103–107. Weinberg AD, Engingro PF, Miller RL, Weinberg LL, Parker CL. Death in the nursing home: Senescence, infection and other causes. J Gerontolog Nurs 1989; 15(4): 12–16. Nicolle LE, Garibaldi RA. Infection control in long-term care facilities. Infect Control Hosp Epidemiol 1995; 16:348–353. Berman P, Hogan DB, Fox RA. The atypical presentation of infection in old age. Age Ageing 1987; 16:201–207. Samily AH. Clinical manifestations of disease in the elderly. Med Clin North Am 1983; 67:333–344. Castle SC, Norman DC, Yeh M, Miller D, Yoshikawa TT. Fever response in elderly nursing home residents. Are the older truly colder? J Am Geriatr Soc 1991; 39: 853–857. Darowski A, Najim Z, Weinberg JR. The febrile response to mild infections in elderly hospital residents. Age Ageing 1991; 20:193–198.

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13.

Weinberg AD, Pals JK, McClinchey-Berroth R. The source of fever and the effect of acetaminophen use on time to diagnosis in febrile long-term care residents. Nurs Home Med 1996; 4:340–347. Yoshikawa TT, Norman DC. Approach to fever and infection in the nursing home. J Am Geriatr Soc 1996; 44:74–82. Smith PW. Consensus Conference Participants. Consensus conference on nosocomial infections in long-term care facilities. Am J Infect Control 1987; 15:97–100. Zimmer JG, Bentley DW, Valenti WM, Watson NM. Systemic antibiotic use in nursing homes. A quality assessment. J Am Geriatr Soc 1986; 34:703–710. AMDA. Clinical Practice Guideline: Altered mental states (E. Tangalos, Chairman). Columbia, MD, American Medical Directors Association, 1998. Gross C, Lindquist RP, Wolley AC, Granieri R, Allard K, Webster B. Clinical indicators of dehydration severity in elderly patients. J Emerg Med 1992; 10:267–274. Nicolle LE. Urinary tract infections in long-term care facilities. Infect Control Hosp Epidemiol 1993; 14:220–225. Arbo MDJ, Snydman DR. Influence of blood culture results on antibiotic choice in treatment of bacteremia. Arch Intern Med 1994; 154:2641–2645. Bartlett JG, Mundy LM. Current concepts: Community-acquired pneumonia. N Engl J Med 1997; 336:243–250. Mylotte JM, Naughton B, Saludades C, Maszarovics Z. Validation and application of the pneumonia prognosis index to nursing home residents with pneumonia. J Am Geriatr Soc 1998; 46:1538–1544. Mylotte JM, Bentley DW. Infection control in subacute care. Clin Geriatr Med 2000; 16(4):805–816. Friedman C, Barnette M, Buck AS, Ham R, Harris JA, Hoffman P, Johnson D, Manian F, Nicolle L, Pearson ML, Perl TM, Solomon SL. Special communication: Requirements for infrastructure and essential activities of infection control and epidemiology in out-of-hospital settings: A Consensus Panel report. Am J Infect Control 1999; 27:418–430. Weinberg AD, Pals JK, Wei JY. The utilization of intravenous therapy programs in community long-term care nursing facilities. J Nutr Health Aging 1997; 1:161–166. Weinberg AD. The medical director’s role in screening high-acuity admissions to subacute units. Ann Long Term Care 2000; 8(2):72–78. Jones JS, Dwyer PR, White LJ, Firman R. Patient transfer from nursing home to emergency department. Outcomes and policy implications. Acad Emerg Med 1997; 4:908–915. Rubenstein LZ, Ouslander JG, Wieland D. Dynamics and clinical implications of the nursing home-hospital interface. Clin Geriatr Med 1988; 4:471–491. Teresi JA, Holmes D, Bloom HG, Monaco C, Rosen S. Factors differentiating transfers from long-term care facilities with high and low transfer rates. Gerontologist 1991; 31:795–806. Fried TR, Gillick MR, Lipsitz LA. Short-term functional outcomes of long-term care residents with pneumonia treated with and without hospital transfer. J Am Geriatr Soc 1997; 45:302–306. Thompson RS, Hall NK, Szpiech M, Reisenberg LA. Treatment and outcomes of pneumonia in the elderly. J Am Board Fam Pract 1997; 10:82–87.

14. 15. 16. 17. 18. 19. 20. 21. 22.

23. 24.

25. 26. 27.

28. 29.

30.

31.

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Mott PD, Barker WH. Treatment decisions for infections occurring in nursing home residents. J Am Geriatr Soc 1988; 36:820–824. 33. Ouslander JG, Osterweil D, Morley J. Medical Care in the Nursing Home, 2nd edition. New York, McGraw-Hill, 1997. 34. AMDA. Protocols for physician notification: Assessing patients and collecting data on nursing facility patients: A guide for nurses on effective communication with physicians. Columbia, MD, American Medical Directors Association, 2000:1–33. 35. Nicolle LE, Strausbaugh LJ, Garibaldi RA. Infections and antibiotic resistance in nursing homes. Clin Microbiol Rev 1996; 9:1–17.

3 Epidemiology and Special Aspects of Infectious Diseases in Aging Thomas T. Yoshikawa Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California

I. EPIDEMIOLOGY OF INFECTIOUS DISEASES A. Pre-Antibiotic Era Infectious diseases have assumed an important role in the evolution of the human race and the history of mankind. Survival of man during the prehistoric era depended on avoiding predators. Subsequently, the ushering in of civilization brought new threats for survival. Infectious diseases became the major cause of death and disability until the mid-20th century. Outbreaks such as smallpox, plague, cholera, typhoid fever, diphtheria, tuberculosis, and typhus fever have been responsible for the deaths of millions of people (1). As recently as 1918, an international epidemic of “Spanish flu” (strain of influenza virus) accounted for 21 million deaths in all parts of the world, including approximately 550,000 deaths in the United States (2). In addition, certain infections resulted in death and often caused severe disabilities, deformities, and functional incapacities, such as mumps, measles, scarlet fever, rheumatic fever, pertussis, poliomyelitis, and syphilis (1). Not surprisingly, childhood mortality was very high. It is for this reason that, up until the mid-1900s, life expectancy was relatively limited (approximately 47 years in the United States) (3). B. Germ Theory and Its Impact Until the acceptance of microbes as causes of infections, the fundamental doctrine that explained the cause or causes of diseases was the doctrine of humoral pathol27

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ogy, that is, man’s health and temperament were affected by four body fluids or humors: blood, phlegm, black bile, and yellow bile (4). In the early 1800s, the concept of contagions and contagiousness, that is, diseases could be communicable and transmitted to others, laid the foundation for the establishment of the age of bacteriology and germ theory of medicine. In the mid- to late-1800s, discoveries by Louis Pasteur (pasteurization; microorganisms were the cause of disease; vaccines for anthrax, rabies, and swine erysipelas), Joseph Lister (antisepsis), and Robert Koch (cause of tuberculosis; tuberculin skin test) led to the eventual acceptance of the microbial cause of infections, hence, the “germ theory” of medicine (4). The clinical impact of the germ theory was the development and implementation of antisepsis, antibiotics, vaccination, sanitation, and public health measures. These practices and processes reduced deaths and complications from infectious diseases in industrialized nations beginning in the latter half of the 20th century and resulted in the increase in life expectancy observed during the past 50 years in such nations, including the United States. However, in less developed parts of the world, infections continue to be the primary cause of mortality, accounting for one-third of all deaths worldwide. The World Health Organization estimates that 50,000 deaths occur each day in the world from infectious diseases (4). With the increase in life expectancy, the population of aging adults has grown rapidly, including those requiring long-term care (see Chapter 1.) Heart disease, cancer, and stroke have become the leading causes of death in both young and older adults (5). However, infections remain an important cause of morbidity and mortality in the elderly population, especially the very old and frail elderly (6). Currently, there is no evidence that aging is associated with greater vulnerability to all infectious diseases. The available data indicate that select infections are especially important in the elderly person because of their higher frequency (incidence, prevalence) and/or poor outcomes (higher morbidity, mortality, or both). These infections are listed in Table 1 (7).

Table 1 Important Infections in the Geriatric Population Urinary tract infection Respiratory tract infection (pneumonia and bronchitis) Tuberculosis Skin and soft tissue infections (e.g., infected pressure ulcer, herpes zoster) Intra-abdominal infections (diverticulitis, cholecystitis, appendicitis) Bacterial meningitis Infective endocarditis

Epidemiology of Infectious Diseases

29

In the very old and frail elderly, such as residents in long-term care facilities (LTCFs), the susceptibility to and mortality from infections greatly increase. Pneumonia, urinary tract infection, and skin/soft tissue infections, such as cellulitis and infected pressure ulcers, are the most common infections found in residents of LTCFs (8,9). Moreover, within a closed institutional setting and environment, other types of infections become prominent. These include a variety of infectious diarrheas (see Chapter 18), scabies (see Chapter 17), viral hepatitis (see Chapter 19), and infections caused by multidrug-resistant bacteria (see Chapters 22, 23, and 24).

II. SPECIAL ASPECTS OF INFECTIONS IN THE ELDERLY A. Clinical Manifestations Infection is now well known to be an important cause of morbidity and mortality in elderly persons. However, the clinical diagnosis of infectious disease in older patients is often difficult and overlooked. The clinical manifestations of infections in the frail elderly LTCF resident may be atypical or absent (see Chapter 6). Fever may not be detectable in older persons with serious infections (10). In frail LTCF residents, studies have shown that baseline body temperatures may be subnormal, and febrile responses to an infection may occur but go unrecognized because the “fever” fails to reach a predetermined criterion (e.g., 101°F [38°C]). In such cases, a change in body temperature of at least 2°F from baseline should be interpreted as a possible “febrile” response (11). It also has been proposed that the absolute criterion for fever be lowered in frail elderly persons, that is, 99°F (37.2°C) for oral temperature and 99.5°F (37.5°F) for rectal temperature (12). B. Increased Susceptibility to Infections The increased susceptibility of older people to select infections may be a multifactorial process. A “normal” process of aging is the phenomenon of immune dysregulation or dysfunction (see Chapter 4). It is most likely the interrelationships between age-related immune dysregulation and age-associated chronic diseases that affect immune processes that place the older, frail LTCF resident at high risk for infectious diseases (13). In addition, other factors such as nutrition (see Chapter 5) and chronic use of antibiotics (see Chapter 11) have an impact on the risk, severity, and types of infections found in the geriatric population. The risk or severity of an infection can be simply illustrated in an equation that includes innate microbial factors (virulence), quantity of exposure to microorganisms, and

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host resistance: virulence  inoculum size Infection (risk/severity) ⬇  host resistance This relationship states that infection risk or severity is directly proportional to the virulence of the pathogen and quantity of organisms, and inversely proportional to the integrity of host resistance (14). Certainly, frail LTCF residents are being exposed more to highly virulent organisms by virtue of several pathogens having resistance to multiple antibiotics (e.g., methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci [VRE]). The quantity of microorganisms to which these residents are exposed can be enormous, especially when they experience aspiration pneumonia, intra-abdominal infections, and infected skin/soft tissues (e.g., pressure ulcers). In addition, the age-related changes in immune function and the immune dysregulation associated with underlying chronic diseases reduce the elderly LTCF resident’s resistance to infection. C. Antimicrobial Therapy Chapter 11 provides an in-depth discussion of the principles and approach to prescribing antibiotics for elderly patients with suspected or confirmed infections. Nevertheless, it is important to consider the age-related changes in pharmacokinetics and pharmacodynamics whenever any drug is prescribed to an elderly patient. Dose adjustments and the pharmacological properties of a drug must be carefully determined because of the age-associated alterations in volume of distribution, reductions in renal function, and potential sensitivity of select organs to certain drugs. Moreover, because the vast majority of older patients are taking some type of prescribed or over-the-counter medication, potential drug interactions as well as adverse side effects, must be carefully evaluated before and during administration of an antibiotic (e.g., divalent ion-containing antacids may affect the absorption of many quinolones). Adverse drug events occur more often in the elderly and increase with the number of drugs prescribed (15). It is imperative, therefore, that careful monitoring for adverse events in elderly patients or residents be performed regularly during administration of antibiotics or any other drug. Because elderly persons may not exhibit typical manifestations of drug side effects as described by the drug information packet, it is important to be aware that unexplained changes in cognitive function, behavior, or physical capacity may be attributable to medications. However, close monitoring is especially difficult in LTCFs because of the high level of disability and inability to communicate in many of the residents in these institutions, the limited number of visits made by physicians and other health providers, and lack of immediate availability of laboratory tests in such facilities. Given these limitations, prescribing antibiotics to

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LTCF residents will require careful thought, appropriate indications, and judicious selection.

REFERENCES 1. 2. 3.

4. 5.

6. 7. 8. 9.

10. 11.

12. 13. 14. 15.

Lyons AS, Petrucelli RJ. Medicine: An Illustrated History. New York, Harry N. Abrams, 1978. Crosby AW. Epidemic and Peace, 1918, Part IV. Wesport, CT, Greenwood Press, 1976. U.S. Department of Health and Human Services (DHHS), Public Health Service, National Center for Health Statistics: Health United States 1985. DHHS Publication No. (PHS) 86-1232. Hyattsville, MD, DHHS, 1986. Kupersmith C. Three Centuries for Infectious Disease. An Illustrated History of Research and Treatment. Greenwich, CT, Greenwich Press, 1998. National Center for Health Statistics. Leading causes of death and number of deaths according to age: United States, 1980 and 1993. In: Health United States, 1995. Department of Health and Human Services (DHHS) Publication No. (PHS) 96-1232. Hyattsville, MD, DHHS, 1996. Yoshikawa TT. Geriatric infectious diseases: An emerging problem. J Am Geriatr Soc 1983; 31:34–39. Yoshikawa TT: Important infections in elderly persons. West J Med 1981; 135: 441–445. Yoshikawa TT, Norman DC. Fever in the elderly. Clin Infect Dis 2000; 31:148–151. Bentley DW, Bradley S, High K, Schoenbaum S, Taler G, Yoshikawa TT. Practice guideline for evaluation of fever and infection in long-term care facilities. Clin Infect Dis 2000; 31:640–653. Norman DC. Fever in the elderly. Clin Infect Dis 2000; 31:148–151. Castle SC, Yeh M, Toledo S, Norman DC. Lowering the temperature criterion improves detection of infections in nursing home residents. Aging Immunol Infect Dis 1993; 4:67–76. Norman DC, Yoshikawa TT. Fever in the elderly. Infect Dis Clin North Am 1996; 10:93–99. Castle SC. Clinical relevance of age-related immune dysfunction. Clin Infect Dis 2000; 31:578–585. Yoshikawa TT, Norman DC. Aging and Clinical Practice: Infectious Diseases. Diagnosis and Treatment. New York, Igaku-Shoin, 1987. Wong FS, Rho JP. Drug dosing and life-threatening drug reactions in the critically ill patient. In: Yoshikawa TT, Norman DC (eds). Acute Emergencies and Critical Care of the Geriatric Patient. New York, Marcel Dekker, Inc., 2000:31–47.

4 Impact of Age and Chronic IllnessRelated Immune Dysfunction on Risk of Infections Steven C. Castle VA Greater Los Angeles Healthcare System, and UCLA School of Medicine, Los Angeles, California

I. INTRODUCTION The increased risk and severity of infections in the elderly population is well documented, and immunosenescence, the state of dysregulated immune function with aging, is felt to be a significant contributor to this increased risk. However, of more clinical relevance is the even higher risk of nosocomial infections in longterm care facilities (LTCFs). Surveillance of LTCF-acquired infections by the National Nosocomial Infections Surveillance system has reported a high incidence of 3.82 infections per 1000 resident-days of care, but with significant variability (1). Data vary widely depending on the type of facility, nature of the residents, definitions used for infections, and type of data analysis. Prevalence rates of infection range from 1.6% to 32.7%, and overall incidence rates range from 1.8 to 13.5 infections per 1000 resident-days of care, with equal variability for specific infections such as urinary tract infection or pneumonia. The questions that are raised from these data are: (1) What resident or facility factors contribute to this wide variability of incidence of infections? (2) Can anything be done to reduce the risk of infection by treatment of residents? (3) What impact could changes in infection control policy have on infection rate for a given facility? If the goal is to prevent serious infections in the elderly, it appears the field of geriatric immunology/infectious disease is faced with the tremendous challenge of studying a very diverse population of chronically ill individuals in addition to the study of the very healthy elderly. Grouping individuals by disease severity or 33

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by level of impairment of specific components of immunity may help to advance our ability to improve host defense in an at-risk population (2).

II. IMMUNOSENESCENCE: AGING CHANGES IN IMMUNITY EXCLUDING IMPACT OF DISEASE Immunosenescence is defined as the state of dysregulated immune function that contributes to the increased susceptibility of the elderly to infection and, possibly, to autoimmune disease and cancer (3). This perspective will focus on the relevance that age-related immune dysregulation has on susceptibility to infectious disease; however, there is growing interest in the pathogenetic role of a dysregulated immune system in common age-related illness such as atherosclerosis, Alzheimer’s dementia, diabetes mellitus, or osteoporosis. The immune system is arbitrarily divided into innate (natural) and adaptive (acquired) components, but recent advances in the field have focused attention on the interface between these two components. Extensive studies in inbred laboratory animals and in very healthy elderly humans have identified age-related changes in immunity, which have been essentially limited to phenotypic and functional changes in the T-cell component of adaptive immunity. In an attempt to standardize laboratory methods and isolate aging changes from external changes of disease and medications, studies over the past 15 years have included only the very healthy elderly. This has been accomplished by the exclusion of subjects with evidence of disease or use of medications, by applying rigorous criteria as defined by the SENIEUR Protocol (4). This concept of distinguishing nature (genetic) versus nurture (environment) has long been debated and tends to distinguish the subtle differences in the interests of gerontologists (the study of aging) and geriatricians (the care of the aged). The SENIEUR Protocol criteria exclude subjects with unhealthy lifestyle choices; any clinical information that suggests the presence of infection, inflammation, malignancy, or other immune disorders; and any laboratory data that suggest abnormal organ function as well as anyone on medications for treatment of a defined disease. These stringent criteria exclude 90% of subjects aged 65 or older, 25% of younger subjects, and virtually 100% of the population in LTCFs (5–7). It would appear the original intent of the SENIEUR protocol was to develop a reference population, but it has been applied to exclude subjects with significant external/environmental exposure, which limits our understanding of mechanisms of vulnerability to infections in the at-risk population with underlying chronic diseases. Hence, despite extensive studies on possible mechanisms for age-related changes in T-cell phenotype and function in a very healthy population, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population (4–7).

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III. IMPACT OF CHRONIC ILLNESS ON INFECTIONS SEEN IN THE ELDERLY Despite 90% complete involution of the thymus by age 40, true opportunistic infections are NOT seen among elderly patients, even those with significant chronic disease. This suggests that there is likely compensation for the lost activity of the thymus gland. Infections that are a problem in this population are well known to the clinician, that is, primarily bacterial infections (pneumonia, urinary tract, and skin and soft tissue) and some viral infections (reactivation of herpes zoster, and significantly increased morbidity and mortality associated with influenza virus). In addition, changes in immunity create difficulty in detecting both active (primary and reactivation) and inactive tuberculosis. Response to vaccination, which requires intact cell-mediated immunity to drive the humoral response, is clearly diminished in many different elderly populations as well as in laboratory animals (3,5,6). A. Impact of Age and Chronic Illness on Influenza Age-related changes in immunity likely have the most clinical relevance towards an impaired response to influenza infection and/or immunization to influenza. An estimated 90% of the 10,000 to 40,000 excess deaths attributed to influenza annually in the United States occur in persons 65 years of age or older. The Centers for Disease Control and Prevention Report on prevention and control of influenza states that when the antigenic match between vaccine and circulating virus is close, infection is prevented in 70% to 90% of subjects younger than 65, compared with only 30% to 40% in those 65 years of age or older (8). A past review on antibody response to influenza found that 10 studies identified a decline in antibody response in an aged population, 16 reported no change, and four showed an increased response. This variability is related to both differences between populations and differences in defining a protective antibody response. Influenza vaccine efficacy in elderly persons is a complicated issue for a variety of reasons including the low attack rate and challenge in confirming actual influenza infection. There are also differences in defining an antibody response because older individuals often have higher prevaccination antibody levels compared with younger individuals who have had less exposure to infection and fewer vaccinations. Even if antibody responses were intact, they may not provide the same level of protection as in younger individuals. Thus, for example, in a study reporting on 72 vaccinated elderly who later were confirmed to have influenza infection, 60% of these individuals had antibody titers of 1:40 or higher, and 31% had titers of 1:640 or higher 4 weeks after vaccination (9,10) (see Chapter 20). Not only is vaccine response less in this population, but even when vaccine response appears adequate, protection from infection is lower than in younger adults, which is likely related to the quality of the antibody produced in neutralizing viral pathogenesis. Never-

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theless, despite the low efficacy in prevention of infections, it needs to be emphasized that vaccination in people aged 65 and older has been effective in reducing adverse events. In those 65 years of age or older, vaccination reduced the incidence of hospitalization or pneumonia 50% to 60%, and mortality was reduced by 80%. In a 3-year study on more than 75,000 community-dwelling elderly, there was a 46% (range of 39% to 54%) reduction in all-cause mortality associated with individuals who received influenza vaccination. Antibody response to vaccination (both magnitude and duration) is impaired in those aged 65 and older, but protective benefit to host defense likely occurs because cytotoxic T lymphocyte activity towards both killing efficiency of viral infected cell and duration of activity has been reported to be intact in older subjects (8,9,11,12). Underlying chronic illness dramatically increases the risk of influenza infection and impairs the response to vaccination. The presence of one or two chronic illnesses (such as emphysema, diabetes mellitus, or chronic renal insufficiency) is associated with a 40- to 150-fold increase in the basal incidence rate for influenza pneumonia (11). Whether chronic illnesses, medications, or other related external conditions directly contribute to further compromise of immune competence has not been elucidated. One study on vaccine response in nursing home residents demonstrated only 50% of residents had an adequate response, based upon a definition of a fourfold increase in antibody titers. Furthermore, the response to vaccination did not correlate with nutritional status or dehydroepiandosterone levels (13). Another study in a nursing home setting reported that only 36% of 137 vaccinated residents demonstrated a rise in antibody titer, and there was no correlation with age, body mass index, or functional status, as measured by the Barthel Index (14). B. Impact of Age and Chronic Illness on Pneumonia and Tuberculosis The risk and severity of pneumococcal pneumonia and tuberculosis increase with age. The incidence of pneumococcal infection is high in the first 2 years of life, then declines through adulthood, and finally increases dramatically in the geriatric population. Mortality is higher in elderly subjects and rises with advanced age, approaching 80% in those older than age 85. Rates of bacteremia and meningitis from the pneumococcal infection are higher in the elderly. In fact, unlike all other age groups, mortality from pneumococcal pneumonia has actually increased in those older than age 75 since the antibiotic era (1950 vs 1985). Efficacy of the pneumococcal vaccine in preventing infection has been difficult to demonstrate in randomized control trials but has been reported to be 50% to 80% effective in case series. Five years after vaccination, the efficacy remains about 70% for those younger than age 75, but only 53% in subjects 75 to 85, and only 22% effective in those older than age 85 (15,16) (see Chapter 20).

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The overall case rate for tuberculosis declined 26% in the United States between 1992 and 1997, with the highest number of cases reported in the 25 to 44 age group, which is a reflection of the human immunodeficiency virus (HIV) epidemic (see Chapter 15). Prior to this epidemic, tuberculosis case rates had an upward inflection point at age 75, due to both reactivation and primary cases of residents in institutional settings and community cases going undetected (11). The disease in the elderly remains largely distinct from tuberculosis in association with HIV infection, and the majority of the cases remain isoniazid sensitive. Differences in presentation between young and older persons with tuberculosis include more subtle presentation (less pronounced cough, night sweats or X-ray findings), and skin testing is difficult to interpret due to both a waning of delayed hypersensitivity (false negative for inactive and active disease), but a more pronounced booster effect (false positive for “conversion”). Mouse studies on tuberculosis show increased susceptibility with minor shifts in the host response. Briefly, it appears that in older animals there is a delayed recruitment of CD4
T cells, with less interferon gamma production. Hence, the infection tends to disseminate more and eventual containment is less. Adoptive transfer studies show that transfer of young T cells into old animals reverses many of these changes (17). C. Changes in Immunity in Subjects with Herpes Zoster Infection The incidence of herpes zoster dramatically increases in individuals older than age 75 (see Chapter 17). Younger individuals who develop active zoster infections have an increased association of immunosuppressive illness, but outbreaks are not associated with occult malignancy in older individuals. Factors that control or predict reactivation of latent infections are not known. Limited epidemiological studies have shown that blacks have less risk of developing zoster than whites, but measures of stress were not significantly associated with herpes zoster. Risk factors associated with the development of postherpetic neuralgia, such as the degree of immunological recall to the virus, have not been studied (18,19). No careful studies of immune changes in subjects who have had an outbreak of acute zoster or postherpetic neuralgia have been done; there are no studies to assess association of herpes zoster with subsequent development of bacterial, tubercular or influenza infection, or response to vaccination. D. Risk Factors for Colonization with Resistant Bacteria Colonization of resistant bacteria in residents of LTCFs, including methicillinresistant Staphylococcus aureus, vancomycin-resistant enterococci, aminoglycoside-resistant enterococci, and multidrug-resistant gram-negative bacilli varies significantly from facility to facility (see Chapters 21–24). Colonization may be

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more common in LTCFs than in acute care settings, whereas infection from these organisms is less common. Epidemiological markers of risk of colonization and infection are generally any marker of end-stage illness and frailty, including prior acute hospitalization, length of stay in an LTCF, poor functional status, recurrent urinary bladder catheterization, urinary incontinence, pressure ulcers, and gastrostomy tubes (20). Despite these markers of frailty, no studies have correlated colonization with resistant bacteria with specific changes in immunity, poor vaccine response, or risk of influenza or other bacterial infections. Hence, efforts toward prevention of colonization with resistant bacteria have included control/appropriate use of antibiotics and infection control measures of hand washing and appropriate isolation protocols.

IV. AGE-RELATED CHANGES IN COMPONENTS OF IMMUNE RESPONSE A. Innate and Acquired Immunity The immune response consists of two interactive components, an innate (natural) and an acquired (adaptive) response. Innate immunity is less studied but has cellular components, that is, macrophages, polymorphonuclear (PMN) cells, natural killer (NK) cells, and dendritic cells (DCs); and noncellular components, which involve recognition molecules, such as C-reactive protein, serum amyloid protein, mannose-binding protein and the complement cascade. The noncellular components bind carbohydrate structures that do not occur in eukaryotes to help differentiate invading pathogens from self, which are then eradicated by the cellular component (3). Adaptive or acquired immunity has unique characteristics: (1) there is a specific response to a given antigen; (2) interaction of cells is required to activate either a cellular (cytotoxicity) and/or humoral (antibody) response; (3) memory is present, which enables more rapid response upon subsequent rechallenge of the same antigen; and (4) both the cell-mediated and humoral functions are dependent on T cells. To initiate an adaptive immune response, T cells must be activated by functional antigen-presenting cells (APC). The degree of interaction of both T cells and APC can influence the subsequent type, quality, and quantity of immune response. Hence, it is at this key interface between innate and acquired immunity that regulation of turning on or off of a response occurs (3,11,21,23). Interaction between the different immune cell types that constitute these components of host defense is carried out by the relative mix of cytokines, hormone-like proteins that act locally in directing the characteristics of an inflammatory response, and the ability of effector cells to differentiate or respond to specific signals, both of which are likely affected by aging and chronic illness. In general, activation of acquired immunity that involves a cell-mediated immune re-

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sponse and is protective against most infectious agents is described as a T helper 1 (Th1) response and is associated with high levels of the cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-). In contrast, a T helper 2 (Th2) response, which is associated with allergic or parasitic infections but not associated with clearance of most bacterial or viral infections, is associated with high levels of IL10, IL-4, and IL-5 but low levels of IL-2 and IFN-. The relative concentrations of so-called proinflammatory cytokines, defined as those that upregulate a Th1 response (such as IL-12, IL-1, tumor necrosis factor alpha), or anti-inflammatory cytokines (important in turning off an inflammatory response such as IL-10, transforming growth factor beta, or IL-1 receptor antagonist) that are produced in local tissues, circulating APC including DCs, or by existing tissue macrophages, allow further refinement of the eventual outcome of an inflammatory response by influencing gene activation in effector immune cells (3,11,21–23). Mature DCs are required for efficient activation of influenza-specific cytotoxic (memory CD8
) T cells (24). Hence, the differentiation of regulatory APC at the site of inflammation is important in determining the quality of the subsequent immune response, either due to the age-related changes in the cytokine mix at the site of inflammation or to cell-specific changes from aging or chronic disease. Examples of differentiation-dependent measures of the efficiency of the interaction include the ability of T-cell binding to APC, IFN- production, and the ability to generate influenza-specific cytotoxic T cells. Hence, adjuvants that may affect the ability of the DC to differentiate or mature should be considered to improve the suboptimal vaccine response seen in residents of LTCFs. B. Age-Related Changes in Acquired Immunity The overall impact of age on host immunity is thought to occur primarily along two mechanisms. The first is replicative senescence that may limit T-cell clonal expansion (the Hayflick phenomenon or loss of telomerase activity/telomere length, and may be more related to exposure to antigen than age). The second is developmental changes associated with involution of the thymus that precedes dysfunction of the T-cell component of adaptive immunity. Studies have shown a decrease in telomere length with age in T cells and B cells; recently, however, it was demonstrated that there was no significant change in telomerase activity upon stimulation of cells (25). This study may not have included individuals with repeated exposure to antigen (perhaps in individuals with chronic illness), but it suggests that age-specific changes are more due to developmental changes in T cells. Several recent reviews have summarized extensive studies on changes in T-cell function with aging (26–29). The age-related decline in T-cell function is preceded by involution of the thymus gland (cortex involutes much more than the medulla), with dramatic declines in thymic hormone levels, which has been described in both animals and humans. In addition, changes in bone marrow stem

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cells have also been described that are distinct from thymic changes. These changes are thought to result in a shift in the phenotype of circulating T cells, with a decrease in the number of naïve T cells (CD45RA
CD4
), and a relative accumulation of memory T cells (CD45RO
CD4
). In addition, the memory cells that remain include a spectrum of normal functioning and hypofunctioning T cells in comparison with younger adult controls. The decrease in functioning cells results in impaired proliferative capacity and IL-2 and IL-2 receptor expression. These changes can be traced to defective upstream postreceptor signaling at multiple steps, including the phosphorylation of mitogen-activated protein kinases (29). At the same time, there appears to be a propensity towards a shift to a Th2 anti-inflammatory response, as evidenced by an increase in IL-10 production (3,11,30). A wide spectrum of findings have been reported, but the healthier the population, the less impact on changes in T-cell function can be identified. Agerelated changes in T-cell cytokines other than IL-2 and IL-10 have demonstrated a much more varied response, especially IFN- and IL-4, which may relate as much to different species (mouse studies differ markedly from humans) and the type of stimulation. Finally, despite the rather universal changes in T-cell response with age, the relevance is unclear. In vitro support of antibody response of T cells has been shown to be impaired with age (9), but impaired proliferative response, even to specific antigen, was not able to predict impaired antibody response to influenza immunization (9). Studies on changes in CD8
cells are much less numerous and have described some age changes, with impaired binding to targets, but once bound, killing capacity appears intact with aging (11,23). Changes in B cells are much less clear but appear to have some similarities to T-cell age-related changes. B cells from older individuals show impaired activation and proliferation that also may be related to changes in costimulatory molecule expression (11,23). Both the primary and secondary antibody responses to vaccination have been impaired, with the degree of impairment being greater when T-cell involvement is required to drive the antibody response (usually related to the complexity of the antigen). The specificity and efficacy of antibodies produced in older individuals is lower than in younger populations (11,27). C. Interaction Between Innate and Acquired Immunity with Aging Age-specific changes in immunity have been largely limited to the T-cell compartment of acquired-immunity. Antigen-presenting cell function in healthy elderly is intact, but infection rates are increased in chronically ill elderly. Thus, it is surmised that the impact of chronic illness on host immunity may be manifested by impaired efficiency of interaction of innate and acquired immunity. Because the innate component of immunity is critical to both the number of immunocompetent units, as well as the magnitude of the immunological burst upon

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activation, it very well could be the target of chronic illness in reducing immune competence beyond normal age-related changes (2). Evidence, for the most part, has suggested innate immunity remains intact or is upregulated with aging. The frequently reported nonspecific increase of proinflammatory substances produced by the innate immune system and downregulation of specific immunity may reflect a compensatory event by either component, with causality unclear (2,11,17). In SENIEUR Protocol Healthy elderly, larger numbers of DCs were generated from circulating immune cells in comparison with younger adults, and DCs from elderly were effective in restoring proliferative capacity and in preventing the development of apoptosis (programmed cell death) in T cells grown to senescence (no longer able to proliferate) in culture (31,32). Likewise, antigen presentation capacity of circulating APCs has actually been shown to be higher in communitydwelling elderly in comparison with younger adult controls, and was associated with higher IL-12 and IL-10 levels (30). Preliminary studies in a nursing home population with chronic illness suggests a reversal in APC function, with impaired antigen presentation, impaired differentiation as manifested by reduced surface marker expression of major histocompatibility complex (MHC) class II and CD40 and no increased levels of the proinflammatory cytokine IL-12 (33, unpublished data). Hence, whether APC function, and DC in particular, is the specific target or the final common pathway of lost immune competence from chronic illness is unclear. The differentiation of DC has been identified as a key variable in the stimulation of effector T-cell function (IFN- production and cytotoxic T-cell function), and will be considered an important target for immunotherapeutic adjuvants to improve antigen delivery and boost immunity in general (24). The production and interaction of cytokines produced by cells of innate immunity are very complex. The timing and relative signal strength of these cytokines are crucial to the overall priming of the acquired immune response. Multiple studies suggest that there is a nonspecific increase in production of proinflammatory proteins in the aged population. Animal studies show exquisite sensitivity in the old animals to bacterial endotoxins, with significantly more endorgan inflammation (15). Low-level, nonspecific autoimmunity throughout different tissues may play a role in gradual loss of reserve capacity of a given organ system, a hallmark of aging, as well as a subsequent nonresponsiveness of immunity to infectious pathogens. Studies on age-related changes in proinflammatory cytokines show varied findings, most likely related to the very complex nature of response to cytokine networks, but most have shown an increase in stimulated production of IL-6, IL-8, and TNF-alpha, and a decrease in IL-1 (3,11,23,34). A recent review on IL-6 and aging describes 14 studies that report increases in IL-6 (34). Interleukin-6 itself has been shown to be inhibitory to TNF-mediated mycobacteriostatic activities in macrophages (35). Chronic illness likely contributes to further dysregulation of control of immune response. A recent study compared IL-2 and IL-6 levels in young and el-

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derly healthy and “almost healthy” populations by including individuals who did not meet the SENIEUR protocol because of a lack of regular exercise and the use of medications for conditions such as hypertension or osteoarthritis. The almost healthy group demonstrated lower levels of IL-2 and higher levels of IL-6 in both young and old age groups, with the most pronounced changes in the elderly almost healthy population (4). Table 1 summarizes the components of the immune system, the impact of age and chronic illness on immunity, and the interaction between innate and acquired immunity.

Table 1 Summary of Immunity, Aging, Chronic Diseases, and Their Interactions Innate immunity

Interface

Key elements

NK cells- Surveillance & infected cell killing PMN- Migration to sites of infection; phagocytosis, local inflammatory cells rescue PMNs; production of ROS for killing M/APC- Phagocytosis, killing of organisms, regulation of cytokines, wound healing

T cells- Provide long-term memory, direct lysis of infected cells, or rapidly amplify response production of proinflammatory cytokines (IL-2, IFN-). B cells- Production of antibodies to antigen; require help from T cells, stimulation of M/APC’s

Aging effects

NK cells- Incr cell number compensates for decr in efficiency; low count is associated with 3 incr mortality PMN- Tissue migration is intact in healthy elders M- Less efficient tumor lysis stimulation response to IFN-

Impact of chronic disease

NK- Little studied PMN- Tissue migration impaired in chronic bronchitis, brittle DM; very high oxidants produced in association with atherosclerosis M- Shown to be inhibitory to killing response to tuberculosis in lungs NK- Natural killer cells PMN- Neutrophil, polymorphonuclear cell M- Macrophage/monocyte APC- Antigen presenting cells GM-CSF- Granulocyte-macrophage colony-stimulating factor LPS- Lipopolysaccharide

NK- Produce proinflammatory cytokines IL-12 PMN- Cytokines from other cells (GM-CSF, IL-2, LPS) prevent PMNs from rapid cell death M- Antigen presentation requires Ms, and signals to T cells determine quality of immune response M-T cell: Many studies show impared response to PHA, likely due to decr in costimulatory molecule function; incr in IL-10 (antiinflammatory) occurs instead and is either a cause or consequence of incr nonspecific inflammation with aging Suggestion of more impairment of interaction with coexisting disease and little or enhanced response in very healthy/elderly IFN-  Interferon-gamma IL- Interleukin Decr/incrDecrease/increase PHA- Phytohemagglutinin DM- Diabetes mellitus

Ag- Antigen Ab- Antibody ROS- Reactive oxygen species

Abbreviations

Acquired immunity

T cells- Memory cells accumulated are much slower to divide, and produce less IL-2, more IL-10. B cells- Produce more auto Ab (to self); levels of Ab remain stable, but specificity for antigen, pathogen decr Further impairment due to loss of stimulation of APC

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V. IMMUNE POTENTIATING EFFECTS OF MEDICATIONS AND DIETARY SUPPLEMENTS A. Modification of Immunity with Nutritional Treatments in Elderly with Nutritional Deficiencies Persons with protein energy undernutrition generally have associated micronutrient deficits. Specific nutrient deficiencies are also possible in individuals without gross undernutrition, but who may not have adequate resources in preparation of balanced meals. Elderly subjects who all met the SENIEUR Protocol but differed in having slightly low serum albumin values (3.0 to 3.5 g/dL) underwent a comparison of immune response. In comparison with those subjects with normal albumin values, the group with the lower albumin had significant decrease in proliferation to phytohemagglutinin, lower IL-2, and decrease in delayed-type hypersensitivity testing. However, there was less of a difference to antibody response to influenza vaccine (36,37). Micronutrient deficits are associated with alteration in immune parameters, especially deficits in zinc, selenium, folic acid, vitamin B-6, and vitamin E. The impact of zinc deficiency on immunity has been extensively studied, as zinc is a cofactor in many postreceptor activation steps that are essential to cell proliferation (see Chapter 5). Zinc deficiency has been found to be associated with impaired peripheral blood T-cell counts, impaired T-cell proliferation, decreased IL2 production, and diminished CD8
T-cell cytotoxicity. Zinc deficiency has been associated with progression of some disease that is thought to be due to a shift from a Th1 to a Th2 response, such as is found in leprosy, leishmania, schistosomiasis, and acquired immunodeficiency syndrome (38–40). In vitro models have reproduced this clinical observation, as zinc-deficient subjects have reduced production of IL-2 and IFN- but no change in Th2 cytokines of IL-4, IL-6, and IL10 (41). Of note, children with protein energy malnutrition have evidence of thymic atrophy and impaired T-cell differentiation, which is reversed by zinc supplementation and correlated with plasma zinc levels. In addition, it has been shown in several tissue culture conditions that zinc deficiency is associated with increased activation of apoptosis of both endothelial cells as well as T cells, which is reversed by zinc supplementation (42). Hence, the ability of local tissues and APCs in stimulating an appropriate immune response may be impaired in the presence of zinc deficiency due to induction of apoptosis of APCs and/or effector T cells upon activation and less support of a subsequent Th1 immune response. B. Effect on Immunity of Dietary Supplements in Elderly Without Known Nutrient Deficiency Other studies have investigated the immunopotentiation of dietary supplements, even if no deficiency is identified. One study has reported a significant increase in

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CD4
DR
cells in a randomized placebo design with zinc supplementation, but a decline in total CD3
and CD4
cells with vitamin A supplementation (43). Another study randomly assigned physiologic supplementation of vitamins (B6, A, C, E) and trace elements in 96 independently living elderly and evaluated changes in immune parameters and the incidence of infections over a 12-month period. In the intervention group, there were significant increases in percent CD3
, CD4
, and NK cells, with no change in CD8
or B cells. There was a significant increase in proliferative response of T cells to phytohemagglutinin with increases in IL-2 and IL-2 receptor expression, as well as NK activity. There was no significant change in the response to influenza vaccine (39). The supplemented group had less number of days of infection and less duration of use of antibiotics. Likewise, a study randomizing hemodialysis patients to 120 mg of zinc sulfate supplementation after each dialysis showed a significant increase in the serum zinc levels, as well as an increase in the percentage of B cells and the antibody response to influenza vaccination (44). Another group has reported an increase in delayed-type hypersensitivity testing at 12 months after supplementation with ascorbate, beta carotene, alpha tocopherol, folate, retinol, riboflavin, copper, and zinc. There was a significant increase in serum levels of all but retinol, riboflavin, copper, and zinc (38). Topical zinc has been associated with a boost in delayed-type hypersensitivity skin testing in elderly hospitalized patients (45). Finally, a recent randomized control trial comparing zinc acetate lozenges (a 12.8 mg zinc acetate lozenge every 2 to 3 hours while awake) with placebo in 50 ambulatory volunteers within 24 hours of developing cold symptoms showed a significant reduction in duration and severity of cold symptoms but did not demonstrate any change in proinflammatory cytokine levels while on treatment with zinc (46). Vitamin E, an antioxidant, has been found to be deficient in 50% of the population studies of healthy elderly in New Mexico (47–50). There is evidence that vitamin E inhibits the formation of prostaglandin E2 (PGE2). Prostaglandin E2 has been described to be elevated with age in humans and animal models and is associated with decreases in proliferative capacity and IL-2 production, and an increase in IL-10 production, all of which are thought to be associated with aging. Dose response improvements in immune function of old mice when given vitamin E supplementation, including delayed-type hypersensitivity, proliferative response and IL-2 with a decrease in PGE2 have been reported (51)). Similar results were obtained in healthy elderly humans supplemented with 800 IU of vitamin E for 30 days, with significant increases in delayed-type hypersensitivity and IL-2 and a trend toward increased proliferation of lymphocytes (48). Further studies on humans demonstrated that low doses of vitamin E (60 mg/day) were able to increase delayed-type hypersensitivity response, but higher doses were needed (200–800 mg/day) to demonstrate an increase in antibody response to several vaccines (hepatitis B, tetanus, and diphtheria) (48,49) and a 30% lower incidence in self-reported infections for a period of 235 days. In a murine influenza model, vitamin E sup-

Age and Illness-Related Immune Dysfunction

45

plementation showed significant reduction in lung influenza viral titers in old mice, with only modest improvement in young mice (50,51). However, epidemiological studies in elderly subjects have not found any correlation between immune parameters (lymphocyte response, delayed-type hypersensitivity, serum antibody levels) with vitamin E intake (52). In human studies, supplementation of vitamin E has not shown a shift from Th2 to Th1 cytokine profiles after supplementation, although delayed-type hypersensitivity has repeatedly been demonstrated to be boosted with vitamin E, especially in the lowest responders (53). The effect of supplementation of vitamins A, C and E on cell-mediated immunity in long-stay nursing home residents did demonstrate improved T-cell number, CD4/CD8 ratio, and T-cell proliferative response to phytohemagglutinin (54). Another study investigated the individual and combined effects of vitamin C (1 g) and E (400 mg alpha-tocopheryl acetate) on APC cytokines, proinflammatory cytokines, IL-1, IL-6 TNF-alpha, and PGE2 in response to lipopolysaccharide stimulation of peripheral blood mononuclear cells. The combination resulted in the higher increases in cytokines than either vitamin given alone and was also associated with a reduced PGE2 production (55). Other studies using 100 mg of alpha-tocopherol in 52 subjects aged 65 years and older did not demonstrate significant changes in antibody production or T-cell proliferative response (53,56). However, there may be subsets of elders who are more likely to benefit from vitamin E supplementation, especially low immune responders (53,55,57). C. Common Medications That May Have Significant Immunopotentiation In addition to obvious immunosuppressive medications, that is, corticosteroids, nonsteroidal anti-inflammatory agents (including cyclooxygenase type 2 inhibitors), and antineoplastic agents, there are several common medications that demonstrate some evidence of immune potentiation. Studies involving chronically ill individuals who are on multiple medications need to control for these medications in particular. The other approach would be to directly test if these medications have potential impact on boosting impaired immune competence in crossover designs. One class of agents that should be considered include beta adrenergic receptor antagonists (beta blockers) (58–60). Beta blockers have been shown to block the immunosuppressive effects of acute stress (58). One study on patients with dilated cardiomyopathy showed a decrease in the rate of anergy (from 70% down to 20%) with an increase in percentage of T cells and NK cells, and an increase in concanavalin A stimulation of IL-2 receptors, in comparison with those randomized to no beta blockers (61). Histamine has been found to affect immune response in a complex manner. Histamine antagonists, especially type 2 inhibitors, also modulate immune response and have been shown to boost proliferative response of T cells to IL-2, improve healing to herpes zoster, and

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boost delayed-type hypersensitivity response (62). Hormonal agents that appear to have an impact on immunity include sex hormones, growth hormone, and megestrol acetate (63–65). Estrogens are likely to have a complex effect, as women tend to have more autoimmune disorders and diminished skin testing responses (64). Growth hormone levels diminish with aging, whereas supplementation of growth hormone was found to reverse involution of the thymus and was associated with enhanced activation of immune systems, including a 50% increase in Tcell proliferative response and increases in IL2 receptor on T cells (65). Other confounding medical conditions that may alter immunity include stress and depression, as well as any primary disease that affects primary organ function, such as failure of the heart, kidney, or liver. These conditions make it difficult to identify causation of impaired host defense; however, they likely manifest by a limited number of impaired potential T cell-antigen presenting cell functions.

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Stevenson KB. Regional data set of infection rates for long-term care facilities: Description of a valuable benchmarking tool. Am J Infect Control 1999; 27:20–26. Castle SC, Uyemura K, Makinodan T. The SENIEUR Protocol after 16 years: A need for a paradigm shift? Mech Ageing Dev 2001; 122:127–140. Pawelec G. Immunosenescence: Impact in the young as well as the old? Mech Ageing Dev 1999; 108:1–7. Ligthart GJ, Corberand JX, Fournier C, Meinders AE, Knook DL, Hijmans W. Admission criteria for immunogerontological studies in man: The SENIEUR Protocol. Mech Ageing Dev 1984; 28:47–55. Mysliwski J, Bryl E, Foerster J, Mysliwski A. The upregulation of TNFa production is not a generalised phenomenon in the elderly between their sixth and seventh decades of life. Mech Ageing Dev 1999; 107:1–14. Wick G, Grubeck-Loebenstein B. The aging immune system: Primary and secondary alterations of immune reactivity in the elderly. Exp Gerontol 1997; 32:401–413. Rowe JW, Kahn RL. Successful Aging. New York, Pantheon, 1998. Fukuda F, Bridges CB, Brammer TL, Izurieta HS, Cox NJ. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999; 48:1–23. Bernstein E, Kaye D, Abrutyn E. Immune response to influenza vaccination in a large elderly population. Vaccine 1999; 17:82–94. Gravenstein S, Drinka PJ, Duthie EH, Miller BA, Brown CS, Hensley M, Circo R, Langer E, Ershler WB. Efficacy of an influenza hemagglutinin-diptheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak. J Am Geriatr Soc 1994; 42:245–251. Burns EA, Goodwin JS. Immunodeficiency of aging. Drugs Aging 1997; 11: 374–397. Mullooly JP, Bennett MD, Hornbrook MC, Barker WH, Williams WW, Patriarca PA,

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Rhodes PH. Influenza vaccination programs for elderly persons: Cost-effectiveness in a health maintenance organization. Ann Intern Med 1994; 121:947–952. Fulop T, Wagner JR, Khalil A, Weber J, Trottier L, Payette H. Relationship between response to influenza vaccination and the nutritional status in institutionalized elderly subjects. J Gerontol A Biol Sci Med Sci 1999; 54A:M59–M64. Potter JM, O’Donnel B, Carman WF, Roberts MA, Stott DJ. Serological response to influenza vaccination and nutritional and functional status of patients in geriatric medical long term care. Age Ageing 1999; 28:141–145. Butler JC, Spika JS, Nichol KL, Shapiro ED, Breinan RF. Effectiveness of pneumococcal vaccine. Lancet 1998; 351:1961–1962. Hedlund JU, Kalin ME, Ortqvist A, Henrichsen J. Antibody response to pneumococcal vaccine in middle-aged and elderly patients recently treated for pneumonia. Arch Intern Med 1994; 154:1961–1965. Orme I. Mechanisms underlying the increased susceptibility of aged mice to tuberculosis. Nutr Rev 1995; 53(S4):S35–S40. Schmader K. Postherpetic neuralgia in immunocompetent elderly people. Vaccine 1998; 16:1768–1770. Schmader K, George LK, Burchett BM, Pieper CF. Racial and psychosocial risk factors for herpes zoster in the elderly. J Infect Dis 1998; 178 Suppl 1:S67–S70. Kaufman CA, Hedderwick SA, Bradley SF. Antibiotic resistance: Issues in long-term care. Infect Med 1999; 16:122–128. Horan MA, Ashcroft GS. Ageing, defence mechanisms and the immune system. Age Ageing 1997; 26-S4:15–19. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392:245–252. Hirokawa K. In: Pathy MSJ (ed). Principles and Practice of Geriatric Medicine, 3rd edition. New York, John Wiley & Sons Ltd., 1998:35–47. Larsson M, Messmer D, Somersan S, Fonteneau JF, Donahoe SM, Lee M, Dunbar PR, Cerundolo V, Julkunen I, Nixon DF, Bhardwaj N. Requirement of mature dendritic cells for efficient activation of influenza A-specific memory CD8
T cells. J Immunol 2000; 165:1182–1190. Son NH, Murray S, Yanovski J, Hodes RJ, Weng N. Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol 2000; 165:1191–1196. Chakravarti B, Abraham GN. Review: Aging and T-cell-mediated immunity. Mech Ageing Dev 1999; 108:183–206. Hodes RJ, Fauci AS (eds). Report of Task Force on Immunology and Aging. National Institutes of Aging and Allergy and Infectious Disease. US Department of Health and Human Services, March 1996. Cossarizza A, Ortolani C, Monti D, Franceschi C. Cytometric analysis of immunosenescence. Cytometry 1997; 297–313. Miller RA. Cellular and biochemical changes in the aging mouse immune system. Nutr Rev 1995; 53:S8–S17. Castle S, Uyemura K, Crawford W, Wong W, Klaustermeyer WB, Makinodan T. Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12. Exp Gerontol 1999; 34:243–252.

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Meyandi SN, Beharka AA. Recent developments in vitamin E and immune response. Nutr Rev 1996; 56:S49–S58. Meyandi SN, Meyandi M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD. Vitamin E supplementation and in vivo immune response in healthy elderly subjects: A randomized controlled trial. JAMA 1997; 277:1380–1386. Han SN, Meydani SN. Vitamin E and infectious diseases in the aged. Proc Nutr Soc 1999; 58:697–705. Han SN, Meydani SN. Antioxidants, cytokines and influenza in aged mice and elderly humans. J Infect Dis 2000; 182 Suppl 1:S74–S80. Goodwin JS, Garry TJ. Relationship between megadoses of vitamin supplementation and immunological function in a healthy elderly population. J Clin Exper Immunol 1983; 51:647–653. Pallast EG, Shouten EG, de Waart FG, Fonk HC, Doekes G, von Blomberg BM, Kok FJ. Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons. Am J Clin Nutr 1999; 69:1273–1281. Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH, Belfield PW. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: A randomized control trial. Age Ageing 1991; 20:169–174. Jeng KC, Yang CS, Siu WY, Tsai YS, Liao WJ, Juo JS. Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. Am J Clin Nutr 1996; 64:960–965. De Waart FG, Portengen L, Doekes G, Verwaal CJ, Kok FJ. Effect of 3 months vitamin E supplementation on indices of the cellular and humoral immune response in elderly subjects. Br J Nutr 1997; 78:761–774. Beharka AA, Wu D, Han SN, Meydani SN. Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E. Mech Ageing Dev 1997; 93:59–77. Bachen EA, Manuck SB, Cohen S, Muldoon MF, Raible R, Herbert TB, Rabin BS. Adrenergic blockade ameliorates cellular immune responses to mental stress in humans. Psychosom Med 1995; 57:366–372. Hedberg A, Gerber JG, Nies AS, Wolfe BB, Molinoff PB. Effects of pindolol and propranolol on beta adrenergic receptors on human lymphocytes. J Pharmacol Exp Ther 1986; 239:117–123. Feldman RD, Hunningshake GW, McArdle WL. Beta-adrenergic-receptor-mediated suppression of interleukin-2 receptors in human lymphocytes. J Immunol 1987; 139:3355–3359. Maisel AS. Congestive heart failure/LVH: Beneficial effects of metoprolol treatment in congestive heart failure: Reversal of sympathetic-induced alterations in immune function. Circulation 1994; 90:1774–1780. Komlos L, Notmann J, Arieli J, Hart J, Levinsky H, Halbrecht I, Sendovsky U. In vitro cell-mediated reaction in herpes zoster patients treated with cimetidine. Asian Pacif J Allergy Immunol 1994; 12:51–58. Mantonvani G, Maccio A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine in-

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volvement in cancer anorexia/cachexia: Role of megesterol acetate and medroxy progesterone acetate on cytokine down regulation and improvement in clinical symptoms. Crit Rev Oncogenes 1998; 9:99–106. 64. Rook GAW, Hernandez-Pando R, Lightman SL. Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance. Immunol Today 1994; 15: 301–303. 65. Khorram O, Yeung M, Vu L, Yen SSC. Effects of growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. J Clin Endocrinol Metab 1997; 82:3590–3596.

5 Nutrition and Infection Kevin P. High Wake Forest University School of Medicine, Winston-Salem, North Carolina

I. INTRODUCTION Aging is associated with a decline in immune competence and an increased risk of infection (see Chapter 4). Nutritional factors have been shown to play a significant role in age-associated immune dysfunction (1–4), and the prevalence of malnutrition among older adults is greatest in residents of long-term care facilities (LTCFs) (5,6). Reversal of underlying nutritional deficits is an attractive and inexpensive option for reducing morbidity and mortality in elderly residents of LTCFs; however, there are few randomized, controlled trials of sufficient power to clearly define the utility of such interventions for clinical endpoints. Most frequently, surrogate markers of nutrition or immune function (i.e., reversal of previously documented vitamin deficiency, increases in serum albumin, vaccine responses, or delayed-type hypersensitivity reactions) have been the outcomes measured in clinical trials. With this limitation clearly stated, this chapter will review the prevalence, causes, methods of detection, and clinical relevance of malnutrition in residents of LTCFs, and provide evidence-based suggestions for practical interventions to boost immune response and reduce the risk of infection in this at-risk population.

II. PREVALENCE AND CAUSES OF MALNUTRITION IN OLDER RESIDENTS OF LTCFs Global malnutrition, a deficiency of protein and calories, is the most common form of malnutrition in older adults. Estimates of the prevalence of protein and 51

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caloric malnutrition is dependent on the variable used to define malnutrition. If one considers reduced daily intake to reflect malnutrition, the proportion of elderly adults who are malnourished ranges from 2% to 33% in both healthy, freeliving elderly adults and residents of LTCFs. However, using nutritional variables such as anthropometric measures or laboratory determinations (i.e., serum albumin, total lymphocyte count), the estimated incidence of global malnutrition in healthy older adults is 3% versus 15% to 66% in institutionalized populations (6). Residents of LTCFs are at greater risk for global malnutrition for two basic reasons: reduced nutritional intake and increased metabolic demands. Reduced intake in LTCF residents is rarely due to poverty, in contrast to poor nutritional intake in the community, because regulations require that meals meet specific nutritional standards. However, serving the meal does not guarantee that it will be consumed (Table 1). Obviously, many LTCF residents have significant disabilities that reduce their capacity to feed themselves or properly chew and swallow. Many residents may be depressed, have anorexia consequent to comorbid conditions or drugs, or other conditions that reduce the desire for food. Furthermore, the environment of LTCFs may not be conducive to caloric intake for some residents. Many elderly in the community maintain caloric intake through “grazing,” that is, eating small amounts throughout the day. Scheduled times for meals, a short duration of time to complete the meal, a lack of adequate staffing to feed all residents at meal time, and reduced preferences for “institutional” ways of preparing food all contribute to reduced caloric intake in residents of LTCFs (6,7). Finally, cog-

Table 1 Barriers to Voluntary Nutrient Consumption in Older Residents of Long-Term Care Facilities Physical conditions Disability (inability to feed oneself) Medications (see Table 6) Poor dentition/swallowing Gastrointestinal disorders (e.g., peptic ulcer disease, gastroesophageal reflux, constipation) Restrictive diets Cultural/psychosocial Food preferences (based on religious or cultural norms) Social isolation System barriers Inadequate staffing Lack of food between meals (inability of elderly to “graze”)

Cachexia/anorexia of underlying disease (e.g., cancer, infection) Increased metabolic demands (e.g., wound healing, renal disease) Metabolic disorders (poorly controlled diabetes mellitus, thyroid disease)

Bereavement Depression

Restrictive meal times

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Table 2 Common Nutritional Deficiencies in Older, Long-Term Care Facility Residents Nutrient

Prevalence

Comment

Protein/calories

17%–65%

Manifested by wasting, low BMI, low serum albumin, lymphopenia Deficiency more common if measured by dietary intake or corneal cytology than by serum levels Particularly important when LTCF residents placed on isoniazid for tuberculosis prophylaxis/therapy Atrophic gastritis is common in elderly Decreased sunlight exposure and dairy product intake Supplementation documented to improve some vaccine responses in older adults Zinc supplementation to speed wound healing probably only helpful in residents who are zinc deficient

Vitamin A

2%–20%

Vitamin B6 (pyridoxine)

28%–49%

Vitamin B12 Vitamin D

0%–20% 20%–48%

Vitamin E

5%–40%

Zinc

0%–21%

BMI, Body mass index; LTCF, Long-term care facility. Source: Refs. 1, 6.

nitively impaired patients may not perceive hunger and thirst in the same way, thus further limiting their internal drive to consume protein and calories. For many of these same reasons, specific nutritional deficiencies also are more common in residents of LTCFs (Table 2). Vitamins A, B6, B12, D, E, and the trace elements zinc and selenium are most often found to be deficient in residents of LTCFs, with prevalence estimates of 40% to 50% for some micronutrients. Specific risk factors for micronutrient deficiencies in elderly LTCF residents include reduced oral intake (vitamins A, B6, D, E, and zinc), increased metabolic requirements (e.g., zinc for wound healing), decreased exposure to sunlight (vitamin D), and a high prevalence of atrophic gastritis (vitamin B12). Like protein/calorie malnutrition, the prevalence of micronutrient deficiencies again varies widely with the techniques used to measure deficiency. For example, vitamin A, a fat-soluble vitamin that is stored in the liver, is essential for proper immune function and the integrity of skin and mucous membranes. A French study (8) showed that the prevalence of vitamin A deficiency in LTCF residents was 2%, 6%, 21%, or 55% depending on whether serum levels, corneal cytology, urinary excretion after a given oral load of vitamin A, or evaluation of oral intake, respectively, was used as the determinate of “deficiency.” Furthermore, there is significant debate as to what the “recommended” daily amount of vitamins or minerals should be in older

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adults (9). Recommended intakes have tended to focus on the average intake in large population studies rather than the optimal level of intake for the majority of the population. Obviously, these recommendations are usually handicapped by a lack of data as to what is optimal. Finally, recent data suggest that energy requirements predicted by frequently cited methods (such as the Harris-Benedict [H-B] equation) do not accurately reflect the metabolic needs of elderly subjects, overestimating metabolic needs in 20%, and underestimating metabolic need in 35% of LTCF residents (10). The accuracy of the H-B equation-predicted metabolic need is not improved by adding a commonly used “stress factor.” Thus, estimating metabolic or specific micronutrient needs in LTCF residents is difficult based on current techniques. Two excellent recent reviews (11,12) have examined the anorexia of aging, outlining the physiological and pathophysiological causes for reduced caloric intake in older adults. There are many instances in which undernutrition is a consequence of physiology, and thus cannot be modified by earlier recognition or intervention. Specific examples include incurable cancer, a competent patient’s refusal to eat or take supplements, endstage disease such as severe congestive heart failure, or chronic obstructive pulmonary disease. However, undernutrition is often the result of a reversible cause, if recognized (Table 3). Specifically addressing this problem in LTCFs, one study (7) identified 15 modifiable causes for undernutrition in LTCF residents (Table 4). Most of the suggested remedies could be set in place at minimal or no additional cost; others, like increasing or retraining

Table 3 Mnemonic for Identifying Causes of Weight Loss in Older Long-Term Care Facility Residents Medications Emotional problems (depression) Anorexia tardive (nervosa); alcoholism Late-life paranoia Swallowing disorders Oral factors No money (insufficient funds in Medicaid facilities for palatable, individualized diets and consultant dietitian) Wandering and other dementia-related behavior Hyperthyroidism, hyperparathyroidism, hypoadrenalism Enteric problems (malabsorption) Eating problems (inability to feed oneself) Low-salt, low-cholesterol diets Social problems (ethnic food preferences, isolation, “disgusting” food habits of other residents) Source: Ref. 12, with permission.

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Table 4 Reversible Causes of Malnutrition and Suggested Remedies Cause

Method of identification

Corrective action

Staff unawareness

Lack of documentation in chart by MD, RN, or RD

Staff education

Inappropriate use of restricted diets

Patient receiving a restricted diet no longer indicated Review of medications

Replace by ad lib diet

Use of drugs which impair desire or ability to eat Unmet need for eating assistance or self-help eating devices Suboptimal technique of eating assistance Suboptimal dining environment Prescription of maintenance instead of repletion dietary intakes (oral or enteral) Inadequate nutritional support during intercurrent illness Unrecognized febrile illness Unmet need for modified diet Inadequate management of tube-feeding complications Poor dental status Unmet need for dysphagia evaluation Suboptimal treatment of dysphagia

Observation and calorie count

Discontinue or replace offending drug Provide assistance or devices

Observation

Retrain the nursing aide

Observation

Improve the environment

 1.5  RDA of calories and protein prescribed

Increase prescription to 1.5  RDA calories and protein

Weight and/or albumin decline during illness; inadequate nutrition support Daily temperatures reveals elevations Clinical review

Project MD will consult on each NHCU patient during intercurrent illness Identify and treat infections Prescribed indicated modified diet Correct management of complication

Prescribed tube-feeding volume not being administered or absorbed Oral examination Clinical signs suggest dysphagia; evaluation not requested Recommendations of speech pathology not being followed

Prompt dental care Consult speech pathology for swallowing evaluation Speech pathologist retrains ward staff

MD, Medical doctor; RN, Registered nurse; RD, Registered dietitian; RDA, Recommended daily allowance; NHCU, Nursing home care unit. Source: Ref. 7, with permission.

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staff, would require significant resources. However, as outlined in the following sections, there is potential for significantly better outcomes for LTCF residents if malnutrition is recognized. One important and often underrecognized cause of malnutrition in older LTCF residents deserves special focus: depression (and other psychiatric disorders). These disorders account for 22% to 32% of cases of significant weight loss in older LTCF residents (13,14) and community-dwelling elderly (15). Given the prevalence and frequently reversible nature of depression, it is incumbent upon all physicians and physician extenders who care for residents of LTCFs to have a heightened awareness of this disorder.

III. ASSESSMENT OF NUTRITIONAL STATUS AND CONSEQUENCES OF MALNUTRITION IN LTCF RESIDENTS Considerable research has been aimed at identifying at-risk or malnourished LTCF residents. Many identification methods include complex measures not available in most LTCFs. However, a review of the relevant literature suggests a number of indicators, readily available from common data sets, that correlate with more sophisticated measures of nutritional status to help identify those at risk. Recently, one study (16) confirmed that the weight and body mass index (BMI; weight divided by height in kg/m2) measures available in the Minimum Data Set (MDS) closely correlates with more sophisticated anthropometric measures and bioelectrical impedance analysis. In another study, BMI closely correlated with a widely used 30-point scale (Mini-Nutritional Assessment [MNA]) predictive of clinical outcomes in many studies of the elderly (Fig. 1) (17). In that Swedish study, malnutrition (an MNA 17) was present in 33% to 71% of LTCF residents depending on the type of facility. A BMI less than 24 kg/m2 correlated with an MNA score of less than 17, identifying the majority of malnourished elderly. Several studies have documented that a recent loss of more than 5% of body weight, a weight less than 90% ideal body weight for age/gender and complaints of anorexia by patients correlate with malnutrition (6,7,18). It may be obvious, but there is a strong correlation between physical impairment and risk for malnutrition. In a recent study (19), it was reported that malnutrition in elderly subjects (from the community or nursing home), as determined at the time of hospitalization, was much more likely in subjects dependent in at least one activity of daily living (ADL), and dependence for any one of the ADLs investigated (bathing, dressing, transfer, toileting, and eating) was independently predictive of malnourishment. Interestingly, of the comorbid conditions examined, congestive heart failure, dementia, chronic obstructive pulmonary disease, cancer, and diabetes mellitus, only diabetes mellitus was related to nutritional sta-

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Figure 1 Correlation of body mass index (BMI) with a 30-point comprehensive nutritional assessment, the Mini-nutritional Assessment (MNA). Reproduced from Ref. 17 with permission.

tus and was negatively associated with malnourishment. Several laboratory parameters also indicate a likelihood for malnutrition; low serum albumin (4.0 g/dL), total cholesterol (160 mg/dL), total lymphocyte count (1500/mm3), and hemoglobin (13 g/dL) all should raise the possibility of malnutrition in an LTCF resident (6,20,21). Nutritional factors are strongly predictive of subsequent hospitalization, disability, and mortality (6,7,18,21–23). One recent study specifically focusing on LTCF residents (23) evaluated 350 randomly selected residents and determined the value of 96 medical, functional, socioeconomic, and nutritional variables for predicting severe (life-threatening) complications. Only five of the 96 variables were predictive, of which three were nutritional (serum albumin, BMI, and amount of weight loss in the prior year), with the other two being renal function and functional status (ADLs). In a subsequent cohort of 110 residents, the authors found that these five variables could predict life-threatening events with a sensitivity of 88% and a specificity of 65% (23). The impact of any one indicator of malnutrition cannot predict with certainty which patients will live and which will die, nor are there specific data that reversing any one variable (e.g., serum albumin) will improve outcomes. However, the magnitude of the association for some nutritional variables with mortality is strong in elderly populations (reviewed in 20). For every decrease in serum

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albumin of 1.0 g/dL, mortality increases 10% to 22%. Furthermore, there is a fourfold risk of mortality when the total lymphocyte count is less than 1500/mm3, and a tenfold risk of mortality in subjects in whom the total cholesterol is less than 120 mg/dL, even after controlling for the presence of malignancy. Importantly, even well-nourished elderly residents of LTCFs often become malnourished during an acute hospitalization (24) and are more likely to become so than their community-dwelling counterparts (21). These elderly are much more likely to require discharge to a nursing or rehabilitation facility (relative risk [RR] 2.3; 95% confidence interval [1.1–4.6]), experience inhospital death (RR 8.0 [2.8–22.6] and death outside the hospital within 90 days (RR 2.9 [1.4–6.1]). Important and, at times, unavoidable interventions such as “NPO” (nothing per oral) orders without adequate replacement nutrition contribute heavily to the number of subjects malnourished during hospitalization.

IV. NUTRITIONAL INTERVENTIONS TO REDUCE INFECTION AND IMPROVE OUTCOMES IN LTCF RESIDENTS It is evident from the data outlined above that elderly LTCF residents are frequently malnourished, and poor nutritional status is associated with an increased risk of adverse outcomes; however, there are relatively few supplementation trials in LTCF residents (Tables 5 and 6). In most instances, the trials that have been published suffer from a lack of clinically relevant endpoints with regard to infection risk and have been significantly underpowered to detect such benefits. Most studies demonstrate increased caloric intake, increased weight, improved MNA scores, or higher serum levels of micronutrients. A few demonstrate trends toward reduced infection or improved vaccine responses, but frequently, other small studies contradict these findings. To the knowledge of the author, no trial of nutritional intervention in elderly LTCF residents has ever shown improved survival. A. Commercial Formulas/Protein-Energy Supplements Early data (reviewed in 7) suggested that commercially available nutritional supplements sometimes enhanced caloric intake and increased serum albumin and transferrin, but the effect on physical function or infection risk was not assessed. Several studies of oral supplementation of commercially available formulas have been performed in LTCF residents in the last 10 years (25–29), but unfortunately, still leave many questions unanswered. An early retrospective, case-control study (25) demonstrated that oral supplements are usually instituted for weight loss or poor appetite, and that oral supplementation resulted in weight gain back to baseline in the majority of residents. Serum albumin, lymphocyte counts, cholesterol,

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Table 5 Trials of Commercial Formula Supplements in Long-Term Care Facility Residents Total N (n on suppl)

Time/ study type

Johnson (25)

109(56)

Variable/C-C

Kayser-Jones (26)

40(29)

Variable/O

Turic (27)

58(28)

6 weeks/R,P

Lauque (28)

88(37)

2 months/ mixed*

Fiatarone Singh (29)

50(24)

10 weeks/R,P

Author (reference)

Comment Supplements started primarily due to weight loss (71%) and poor appetite (16%); weight regained, but no effect on infection or hospitalization rate; mortality higher in supplemented group (significantly more ill at baseline) Supplements rarely administered or consumed as ordered by the physician (overall mean percentage consumed 55% of that prescribed); supplements often prescribed without adequate evaluation of cause for weight loss; calorie intake of supplement offset by reduced meal caloric intake Compared commercial formula vs a snack three times a day; increased energy/protein/nutrient intake in formula group Good compliance, average energy intake increased 400 kcal/day; weight and mini nutritional assessment scores improved in supplemented residents vs control groups Several parameters (total caloric intake, serum folate/vitamin D) approached significance, but only serum transferrin was significantly improved by supplementation; meal caloric intake declined in supplemented group; no change in performance status vs control

* C-C, Case-control; O, Observational; R, Randomized; P, Placebo-controlled. This study used four groups, one well nourished that did not receive supplements (n  19), two groups of “at risk” subjects randomly assigned to supplement (n  19; provided one of four different supplement types) or no supplement (n  22), and a fourth group of malnourished elderly all provided a supplement (n  24).

60

High

Table 6 Selected Micronutrient Supplementation Trials in Older, Long-Term Care Facility Residents Author (reference)

Total N (n on suppl)

Time/ trial type

Nutrient(s) Vitamins A,C,E Vitamin A

Penn (31)

30

1 month/R,P

Murphy (36)

109(53)

Van der Wielen (32)

33(15)

Single, high dose/R 12 weeks/R,P

Girodon (33)

81(61)

2 years/R,P,F

Zn


selenium or Vitamins A, C, E or both

Fortes (35)

118(88)

3 months/R,P,F

Vitamin A, Zn

, both or neither

Provinciali (37)

384(194)

2 months/R

Zn

or Zn


arginine

Girodon (34)

725(543)

2 years/R,P,F

Zn


selenium or Vitamins A, C, E or both

kcal, thiamine, B6, B12, folate

Comment ⇑ T cells, CD4 cells, lymphocyte responses. No change in infection rate or antibiotic use Significantly increased weight, serum thiamine, vitamin B6, decreased serum homocysteine; no immunologic outcomes measured ⇑ serum selenium levels in Zn


selenium group and BOTH group; ⇓ infectious episodes in the groups receiving Zn


selenium, but not vitamins alone group ⇓ CD3
and CD4
in vitamin A group, ⇑ CD3
, CD4
, CD16
and CD56
lymphocytes Influenza vaccine administered in 3 years; no difference in % responders or mean antibody titer post-vaccination ⇑ serum micronutrient levels, but no effect on DTH responses; improved responses to influenza vaccine in Zn


selenium groups, borderline reduction in respiratory infection in Zn


selenium groups (P  0.06), no effect of vitamins alone

R, Randomized; P, Placebo-controlled; F, Factorial; DTH, Delayed-type hypersensitivity; ⇑, increased; ⇓ decreased.

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and hemoglobin tended to improve, but there were too few residents to allow purposeful conclusions. A trend toward higher mortality was apparent in the supplemented group (8/56 vs. 2/53; P  0.057), but these findings are subject to the significant bias of nonrandomized trials in which the intervention is often performed in a population that is more ill. In fact, in the indicated study, the supplemented group did have an older mean age and were more likely to have a history of stroke or pressure sores. There was no difference with regard to infection or hospitalization. However, a nonrandomized observational study (26) suggested that only slightly more than 50% of the volume of supplement ordered is actually consumed by LTCF residents, and that up to half of residents placed on oral supplements will continue to lose weight. Although not quantified, this study suggested that oral supplement use between meals “destroyed the residents’ appetites” in some cases, reducing the total caloric intake. This issue was also raised in a subsequent, randomized trial discussed below (29). Three recent randomized trials of commercial formula supplementation in older LTCF residents have been published. A study of 53 LTCF residents in four LTCFs in Ohio (27) compared an 8-oz serving of a commercially available supplement with a “snack” at 10 AM, 2 PM, and before bed, and assessed several nutritional variables at 3 and 6 weeks. Significantly greater intake of protein, many vitamins and trace elements, and caloric intake were documented, and the study found no decrease in the energy intake from meals alone. No clinical outcomes of health, infection, or functional status were measured in that study. In a second French study, 88 residents in an LTCF were assessed via the MNA (28). Those with a score of less than 17 (n  24) received supplementation. Those with a score of 24 or higher (n  19) received no supplementation. Those residents with scores of 17 to 23.5 (n  41) were considered nutritionally at risk and randomized in an unblinded fashion to receive oral supplements or not (no placebo provided). Twenty-two were randomized to no supplements. All of the 22 completed the observation period and were therefore included in the analysis. However, of the 19 randomized to receive supplements, six withdrew consent or were admitted to the hospital and were excluded from the analysis. The groups were evaluated at baseline and on day 60. Mean caloric (~25%; ~400 kcal) and protein (~30%; 25–30 g) intake improved in the supplemented groups and did not change in the groups that did not receive supplements. There were too few subjects to determine any differences in other outcomes measured between the randomized groups, even with regard to MNA score, and no information was provided regarding infection risk. The third study randomized and examined 50 LTCF residents in a placebo controlled, blinded trial of an oral liquid supplement and determined the impact of supplementation on caloric intake, serum measures of nutritional status, body composition, and health/physical status (29). There was no effect of supplemen-

62

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tation in any of the outcomes measured, even caloric intake. This was due to the fact that nonsupplemental calories (i.e., intake during meals) fell in the intervention group. Clearly there are issues of power in a study of only 25 subjects per arm, but these are the data available regarding oral supplementation in LTCF residents. In summary, protein-calorie supplements are frequently prescribed in LTCF residents, but compliance is often poor. Furthermore, such supplements inconsistently raise caloric intake due to reduced meal-time caloric intake by some residents. No impact on infection risk or survival has been demonstrated for these supplements in LTCF residents. B. Multivitamin/Mineral Supplements There have been many studies of micronutrient supplementation in elderly subjects. Most have been performed in free-living elderly rather than residents of LTCFs (reviewed in 1,30). In LTCF residents, there are four studies of multivitamin/mineral supplements (31–35), and a few studies of individual micronutrients (35–37) (Table 6). These studies have often shown contradictory results; however, some unifying principles can be gleaned from review of the interventions reported to date. Clearly, micronutrient supplements can enhance vitamin and mineral intake in LTCF residents and increase serum levels of many micronutrients. Furthermore, compliance with such supplementation is excellent and inexpensive. Trace elements, primarily zinc and selenium, may increase post-vaccine antibody titers, raise CD4 cell numbers, and reduce the risk of respiratory infection (33–35,37), whereas vitamin supplementation with vitamins A, C, E or -carotene has little or no effect in the studies outlined to date. One large, well-designed study of vitamin/mineral supplementation highlights the potential benefits and limitations of current data. This study (34) randomized 725 LTCF residents in 25 facilities in a factorial design to receive trace elements (zinc 20 mg
selenium 100 mg), three vitamins (C 120 mg, E 15 mg, and -carotene 6 mg [ 1000 retinol equivalents]), both or neither for 2 years. Mortality was expectedly high in all four groups (~30%) and not different between groups. There was no effect on delayed-type hypersensitivity (DTH) responses, but a greater proportion of subjects in the trace element groups (vitamins
trace elements or trace elements alone) had protective antibody titers after influenza vaccination (P  0.05). Surprisingly, vitamins alone appeared to have a negative effect on antibody titers (P  0.05). There was no effect on urogential tract infections, but a trend toward reduced incidence of respiratory tract infections (P  0.06) occurred in both trace element groups but not in those receiving vitamins alone. These data confirm the findings of a smaller, prior study by the same investigators (33), but in the earlier study, the reduction in respiratory infections in the Zn


selenium groups reached statistical significance. The dose of vitamin E used in this and the previously mentioned study (33,34) was modest, 15

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63

mg/d. It should be noted that higher doses of vitamin E (200 or 800 mg/d) have been found to effectively enhance immune responses (DTH responses and T-cell dependent vaccine responses) in free-living elderly (38,39). Reportedly, a randomized trial of vitamin E supplementation in higher doses is underway in LTCF residents (40). Vitamin A (or -carotene, a vitamin A precursor) supplementation has been extensively studied. The rationale for vitamin A supplementation is strong because it is an essential nutrient for immune function and regeneration of epithelial surfaces in the gastrointestinal tract and respiratory tree, and vitamin A deficiency is relatively common in LTCF residents (8). However, no study has shown benefit from vitamin A supplementation in LTCF residents, and, somewhat surprisingly, some studies have found potential harm (33–36). Thus, based on current data, specific vitamin A supplementation should probably be avoided.

V. SPECIFIC SYNDROMES WHERE NUTRITIONAL SUPPLEMENTATION MAY BE OF BENEFIT A. Pneumonia There have been no specific studies of nutritional supplementation in LTCF residents with pneumonia. However, a recent randomized, single-blind study of a commercially available protein-calorie supplement for 1 month after hospitalization for community-acquired pneumonia in elderly subjects did include LTCF residents (41). The supplement improved nutritional status for a variety of variables measured but, most importantly, functional status was improved at a follow-up visit 3 months later when compared with the placebo group. The study was not powered to detect differences in rehospitalization or mortality and did not perform any measures of immune competence. Nevertheless, short-term (1 month) nutritional supplementation after an episode of community-acquired pneumonia may be of benefit in elderly LTCF residents. B. Pressure Ulcers Debate is considerable over whether nutritional supplementation can prevent or speed the healing of pressure ulcers (42,43). A recent multicenter trial (44) demonstrated a slightly reduced risk of pressure ulcers in a group receiving protein-calorie supplements, but several issues have been raised about this study (45). The caloric intake did not increase in supplemented subjects and the difference in incidence of pressure ulcers was relatively small: 41% in the supplemented group versus 47% in the control group. More widely accepted but based on no more convincing data is the practice of micronutrient (e.g., Zn

) supplementation to assist in healing of pressure ul-

64

High

cers. Most data suggest that if there is a benefit of vitamin/mineral supplementation for healing skin/soft tissue wounds, that it is likely limited to individuals deficient at baseline. Current recommendations are to provide adequate calories (30–35 kcal/kg) and protein (1–1.25 g/kg) to avoid negative nitrogen balance, and zinc at a dose of 220 mg/day (42). Vitamins A, C, and several B complex vitamins are necessary for wound healing, but there are no specific recommendations regarding dosing. C. Urinary Tract Infections One nutritional intervention has been reasonably well studied for the prevention of urinary tract infection (UTI) in elderly subjects: cranberry juice consumption (reviewed in 46). There has been only one study in LTCF residents (47); however, there has been one reasonably sized, randomized trial (48), another small crossover study that demonstrated benefit in the elderly (49), and a variety of studies in younger patients (46). However, there are valid criticisms against all these studies. In the randomized trial (48), the endpoint was reduction of bacteriuria with pyuria (15% in the 300 mL/d cranberry juice group vs. 28% in the control group), not symptomatic UTI. As outlined in Chapter 12, asymptomatic bacteriuria in the elderly does not require therapy. There was a trend toward reduced antibiotic use in the treatment group (1.7 vs. 3.2 antibiotics per 100 patient months) which, if confirmed in a larger study, would be of great value in and of itself. In the LTCF study (47), reported only in abstract form, both cranberry juice (220 mL/d) and capsules of cranberry juice extract were used, and the control group was historical. Five hundred thirty-eight LTCF residents were studied and UTIs reduced from 27/month in the historical control group to 20/month in the treatment group (P  0.01). There may be other benefits of cranberry juice (46). One possible cause for reducing antibiotic use could be a reduction by cranberry juice in malodorous urine, a common trigger for urinalysis and urine culture for institutionalized elderly. In addition, a small study of patients with urostomies who consumed 160 to 330 mL/d of cranberry juice experienced improvement in the skin surrounding the stoma. This could be of benefit in LTCF residents with incontinence and immobility who are at risk for skin breakdown, but no substantive trial testing this hypothesis has been performed.

VI. APPETITE STIMULANTS Appetite stimulants are poorly studied in LTCF residents, but a recent randomized, double-blind trial was reported that indicated megestrol acetate (MA) may be of some value (50). In that study, 800 mg/d of MA or placebo was provided for

Nutrition and Infection

65

12 weeks to LTCF residents with weight loss or low body weight, and then the residents were followed up for an additional 13 weeks for subsequent health outcomes. At the conclusion of the 12-week supplementation period, there was no difference in weight, but appetite and sense of well-being were significantly better in the MA group. However, by the end of the 13-week follow-up period, the MA recipients were more likely to have gained 4 lb or more over their baseline. This approach appears to deserve further study.

VII.

DRUG-NUTRIENT INTERACTIONS

The elderly LTCF resident is likely to be receiving multiple prescription drugs. Increasingly, there is recognition that nutrient-drug interactions can cause serious adverse effects. In a recent study of residents in three LTCFs in New York (51), residents consumed approximately five drugs per patient and, on average, were at risk for 1.4 to 2.7 drug-nutrient interactions per month. With specific regard to infection, this is most likely to cause difficulty with antibiotic administration. Tetracyclines and fluoroquinolones may be poorly absorbed when antacids, multivalent cations (e.g., calcium), or tube feedings are provided. Certain antifungal compounds, particularly itraconazole, may be poorly absorbed with concomitant administration of antacids or hydrogen ion (H2) antagonists/proton pump inhibitors. More likely than nutrients influencing drug metabolism, drugs are likely to influence nutrient intake (Table 7). The most commonly prescribed drugs that are likely to induce anorexia and decrease nutrient intake are antibiotics, antidepressants, and other psychiatric drugs, digoxin, and anti-inflammatory agents. A critical part of nutritional care for elderly LTCF residents is frequent, thorough review of all medications with discontinuation of nonessential therapies.

VIII. CONCLUSIONS Residents of LTCFs are often at risk for malnutrition, and reversible causes of malnutrition are common. Most at-risk residents can be initially identified by information available in the MDS (weight and BMI) and initial screening laboratories (serum albumin, total lymphocyte count). More sophisticated assessments, such as the MNA, have been shown to be valid in LTCF residents. Once identified, data support the correction of underlying medical causes, particularly depression, and the use of nutritional supplements or appetite stimulants to increase caloric and protein intake in LTCF residents to reverse weight loss. However, the role of such supplements for preventing infection is less well defined by currently available data. Current data support the use of trace mineral supplements (20 mg/d Zn

-sulfate and 100 g/d selenium sulfide) in most LTCF elderly, as the ex-

66 Table 7 Drugs that Cause Anorexia in Older Adults Anorectic agents Cardiovascular drugs Digoxin Amiodarone Procainamide Quinidine Spironolactone Gastrointestinal drugs Cimetidine Interferon Psychiatric drugs Phenothiazines Butyrphenones Lithium Amitriptyline Impramine Fluoxetine and other selective serotonin-reuptake inhibitors Anti-infective drugs Most antibiotics Metronidazole Griseofulvin Nutrient supplements Iron sulfate Potassium salts Vitamin D (in excess) Antineoplastics Cyclophosphamide and most others Antirheumatic drugs Nonsteroidal anti-inflammatory agents Colchicine Penicillamine Pulmonary drugs Theophylline Malabsorptive agents Laxatives Cholestyramine Methotrexate Colchicine Neomycin Ganglionic blockers Agents that increase metabolism Theophylline L-Thyroxine (in excess) Thyroid extract Triiodotyrosine (in excess) D-Pseudoephedrine Source: Ref. 11, with permission.

High

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67

pense and risk of adverse effects is small, and there appears to be a reduced risk of respiratory infection. Vitamin supplements have variable effects. Vitamin E at 200 mg/d improves immune responses in healthy elderly and may be of value in LTCF residents, but vitamin A supplementation should probably be avoided. Specific nutritional supplementation may be of value in certain infectious diseases such as recovery from community-acquired pneumonia (protein-calorie supplements) and prevention of UTIs (cranberry juice). Finally physicians should be aware of the potential for antibiotic-nutrient interactions and the effect of anorectic medications on nutrient intake. REFERENCES 1.

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Wright BA. Weight loss and weight gain in a nursing home: A prospective study. Geriatr Nurs 1993; 14:156–159. Wilson MG, Caswani S, Liu D, Morley JE, Miller DK. Prevalence and causes of undernutrition in medical outpatients. Am J Med 1998; 104:56–63. Blaum CS, O’Neill EF, Clements KM, Fries BE, Fiatarone MA. Validity of the minimum data set for assessing nutritional status in nursing home residents. Am J Clin Nutr 1997; 66:787–794. Saletti A, Lindgren EY, Johansson L, Cederholm T. Nutritional status according to mini nutritional assessment in an institutionalized elderly population in Sweden. Gerontology 2000; 46:139–145. Sullivan DH. Undernutrition in older adults. Ann Long-Term Care 2000; 8:41–46. Covinsky KE, Martin GE, Beyth RJ, Justice AC, Sehgal AR, Landefeld CS. The relationship between clinical assessments of nutritional status and adverse outcomes in older hospitalized medical patients. J Am Geriatr Soc 1999; 47:532–538. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part II: Laboratory evaluation. Nutrition 2000; 16:131–140. Kamel HK, Karcic E, Karcic A, Barghouthi H. Nutritional status of hospitalized elderly: Differences between nursing home patients and community-dwelling patients. Ann Long-Term Care 2000; 8:33–38. Volkert D, Kruse W, Oster P, Schlierf G. Malnutrition in geriatric patients: Diagnostic and prognostic significance of nutritional parameters. Ann Nutr Metab 1992; 36:97–112. Sullivan DH, Walls RC. The risk of life-threatening complications in a select population of geriatric patients: The impact of nutritional status. J Am Coll Nutr 1995; 14:29–36. Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly hospitalized patients. A prospective study. JAMA 1999; 281:2013–2019. Johnson LE, Dooley PA, Gleick JB. Oral nutritional supplement use in elderly nursing home patients. J Am Geriatr Soc 1993; 41:947–952. Kayser-Jones J, Schell ES, Porter C, Barbaccia JC, Steinbach C, Bird WF, Redford M, Pengilly K. A prospective study of the use of liquid oral dietary supplements in nursing homes. J Am Geriatr Soc 1998; 46:1378–1386. Turic A, Gordon KL, Craig LD, Ataya DG, Voss AC. Nutrition supplementation enables elderly residents of long-term-care facilities to meet or exceed RDAs without displacing energy or nutrient intakes from meals. J Am Diet Assoc 1998; 98: 1457–1459. Lauque S, Arnaud-Battandier F, Mansourian R, Guigoz Y, Paintin M, Nourhashemi F, Vellas B. Protein-energy oral supplementation in malnourished nursing-home residents. A controlled trial. Age Ageing 2000; 29:51–56. Fiatarone Singh MA, Bernstein MA, Ryan AD, O’Neill EF, Clements KM, Evans WJ. The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders. J Nutr Health Aging 2000; 4:5–12. High KP. Micronutrient supplementation and immune function in the elderly. Clin Infect Dis 1999; 28:717–722. Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH, Belfield PW. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune

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Dignam R, Ahmen M, Denman S, Zayon RN, Wilks T, Shipman C, Wolfert R, Kleban M. The effect of cranberry juice on UTI rates in a long term care facility. J Am Geriatr Soc 1997; 45(Supplement):S53 (p. 169). Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994; 271:751–754. Haverkorn MJ, Mandigers J. Reduction of bacteriuria and pyuria using cranberry juice. JAMA 1994; 272:590. Yeh SS, Wu SY, Lee TP, Olson JS, Stevens MR, Dixon T, Porcelli RJ, Schuster MW. Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: Results of a double-blind, placebo-controlled study. J Am Geriatr Soc 2000; 48:485–492. Lewis CW, Frongillo EA, Jr, Roe DA. Drug-nutrient interactions in three long-termcare facilities. J Am Diet Assoc 1995; 95:309–315.

48.

49. 50.

51.

6 Clinical Manifestations of Infections Dean C. Norman VA Greater Los Angeles Healthcare System, and UCLA School of Medicine, Los Angeles, California

I. INTRODUCTION Infectious diseases are a leading cause of morbidity and mortality in the frail nursing home population and a leading cause of transfer of residents from a long-term care facility (LTCF) to an acute care facility. Higher morbidity and mortality rates in older patients in general result partly because of diminished physiological reserves and altered host defenses brought on by aging and comorbidities. This problem is magnified in residents of LTCFs because of debility caused by chronic disease. Elderly residents of long-term care institutions are typically taking multiple medications. This practice, coupled with age and morbidity-related changes in pharmacology of drugs, including antibiotics, increases the risk for adverse drug interactions in nursing home residents. Infected nursing home residents frequently are transferred to acute care hospitals. Unfortunately, hospitalization may be complicated by nosocomial infection and iatrogenic illness. Furthermore, once hospitalized, the elderly are more likely to undergo invasive procedures and to suffer complications. Vigorous prevention measures to control infectious diseases plus rapid diagnosis and timely initiation of appropriate empiric antimicrobial therapy will reduce the impact of infectious diseases in the long-term care population. However, atypical presentation and variability of diagnostic testing and other factors may delay diagnosis and therapy in a population that can least afford such delays. Fortunately, the differential diagnosis of important infectious diseases in the elderly is somewhat limited and dependent on the clinical setting and the patient’s functional status. Respiratory infections, including pneumonia, and urinary tract and soft tissue infections (acronym “PUS”), as well as gastrointestinal infections 71

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comprise the majority of acute infections in residents of long-term care institutions (1). The types of infections may be limited, but the microbial etiology of infections is more diverse in the elderly when compared with the younger population. In general, a variety of pathogens may account for a given infection. For example, pneumonia in the young is usually caused by relatively few pathogens, such as Streptococcus pneumoniae and Mycoplasma pneumoniae. Urinary tract infection in the young adult is usually caused by Escherichia coli. However, in the older adult a variety of pathogens may cause either of these common infections. A small but significant number of cases of community-acquired pneumonia in the elderly are caused by gram-negative bacilli, and a higher percentage of lower respiratory tract infections in nursing homes is caused by gram-negative bacilli and mixed flora (see Chapter 14). Similarly, urinary tract infection in the elderly in both the community and long-term care setting may be caused by any one of several species of gram-negative and gram-positive bacteria. Chronic indwelling bladder catheter-associated infections are typically polymicrobial. The diverse microbial etiology of urinary tract infections in residents of LTCFs requires obtaining urine cultures before initiation of antibiotic therapy for symptomatic urinary tract infection (see Chapter 12).

II. ATYPICAL PRESENTATIONS OF INFECTION Once an infection develops, the cornerstone of successful treatment is timely diagnosis and the rapid initiation of empiric antimicrobial therapy. Nonclassic presentations of acute illnesses occur often in the frail elderly, and acute infections are no exception. In the nursing home, infectious diseases provide unique diagnostic challenges because of atypical presentations—especially diminished fever responses (described in the next section), the frequent presence of cognitive impairment in nursing home residents, and the lack of availability of timely radiographs or laboratory data. The clinician caring for residents of LTCFs should be aware that virtually any acute change in functional status may herald the onset of a serious infectious disease. These manifestations include, but are not limited to lethargy, anorexia, falls, focal neurologic signs and delirium (Table 1). Changes in mental status from baseline are seen even when the infection does not involve the central nervous system. Common infections may present without classic symptoms. For example, pneumonia may be present without cough, purulent sputum, fever, or chest pain, and the only sign alerting the clinician may be tachypnea; meningitis may occur without a stiff neck; and symptomatic urinary tract infection may at times present solely as a decline in cognitive function without dysuria, urgency, or frequency. Moreover, the presentation of illness may not be in proportion to the severity of the underlying infection, a large percentage of

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Table 1 Nonspecific Presentations of Acute Infection in Nursing Home Patients Diagnostic clues • Anorexia • Any unexplained change in functional status from baseline • Change in baseline body temperature (a decrease may be caused by sepsis) • Decline in cognition • Failure to thrive • Focal neurologic signs (may be a clue to presence of meningitis, endocarditis) • Lethargy • Hypotension (may be a clue to presence of sepsis) • Tachypnea (may be initial finding in pneumonia, sepsis)

elderly women who present with symptoms and signs of pyelonephritis, which are indistinguishable from those of younger women, will be bacteremic, which is in contrast to younger women (2). Localizing peritoneal findings may be delayed in cases of severe intra-abdominal infection (3,4). This is especially problematic in LTCFs, where physicians are rarely present to perform physical examinations at the time of onset of symptoms.

III. FEVER A. Significance of Diminished Fever Response Studies of specific infections in older adults, including pneumonia (5,6), bacteremia (7,8), endocarditis (9,10), nosocomial febrile illness (11), meningitis (12), and intra-abdominal infection (13) confirm that fever, the hallmark of invasive microbial infection, may be blunted or absent in up to one-third of infected elderly patients (14–16). The absence of this cardinal sign of infection has implications beyond confounding clinical diagnosis. First, an absent or blunted fever response to infection is a poor prognostic sign, as demonstrated by a study of several hundred patients with bacteremia and fungemia (17). The results of this study confirmed that those patients responding to bacteremia or fungemia with a robust fever were more likely to survive. This classic study’s conclusion is now well established for many infectious diseases and applies to both young and older adults. Second, although the prognostic significance of the febrile response to infection is clear, it is less well established that fever is an essential adaptive mechanism that is an important host defense in humans. However, there is strong evidence that fever is an important host defense for a variety of other species (18). Cold-blooded animals such as certain types of lizards and fish seek warmer environments in order to raise body temperatures in response to infection. Laboratory experiments confirm that

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fever is an important host defense in these poikilothermic animals (19,20). In fact, enhanced resistance to infection appears to occur with increased body temperature (fever) in a variety of mammalian animal models (18). Therefore, based on these animal data, it can be considered that fever is potentially an important host defense in humans. The effect of fever on host defenses is independent of a direct effect of elevated body temperature on bacterial replication. The exceptions are that physiologically achievable temperature elevations may inhibit bacterial growth directly of Treponema pallidum, Neisseria gonorrhoeae, and certain strains of pneumococci. The mechanism by which fever augments host defenses and improves natural and cellular immune responses appears to be multifactorial; it minimally involves elevating certain monokine and cytokine production and enhancing cytokine activity. These cytokines include interleukins 1 and 6, tumor necrosis factor, alpha interferon, and others. These particular cytokines are also endogenous pyrogens and have many effects on cellular components of the immune response. One effect appears to be to facilitate adherence of leukocytes to endothelial cells and leukocyte migration to extravascular areas of infection. The mechanism by which a significant number of infected older adults fail to mount a febrile response is not known. Potential mechanism(s) have been proposed based on the current understanding of the pathogenesis of fever. The role of cytokines as endogenous mediators of fever has been recently reviewed (21,22). Bacterial products such as lipopolysaccharide (endotoxin) induce macrophages and other cells to produce cytokines that act as endogenous pyrogens. These pyrogens are produced either locally at the site of infection and enter the circulation or by macrophages adhering to endothelium in circumventricular organs of the brain. The pyrogens act on the anterior hypothalamus resulting in a biochemical cascade including the release of prostaglandin E2. This cascade raises the central nervous system “thermostat” (22). These changes result in shivering, vasoconstriction, and various behavioral responses, all of which elevate core body temperature, which then becomes the new baseline. When the infection is over, the thermostat is reset to the previous baseline; sweating and temperature-lowering behaviors occur, thus returning body temperature to normal. These pathways could be affected by aging, and thermoregulation in the elderly appears to be impaired to some degree. This is evidenced by the increased morbidity and mortality in older persons from heat stroke and hypothermia. A variety of endogenous pyrogens results in a lower fever response in older mice compared with younger mice (23–25). Other data in rats demonstrated that intracerebroventricular injection of interleukin 1 results in similar immediate fever responses between young and old animals. This suggests that blunted febrile responses observed in older mammals may result from an inability of peripheral endogenous mediators to reach the central nervous system rather than an unresponsiveness of the central nervous system (26). Other studies have demonstrated diminished production of endogenous pyrogens with age

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in various rodent models (27). Select rodent experiments have yielded evidence that changes in thermogenic brown fat may play a role in the blunted fever response of aging (28). Thus, reduced production and response to endogenous pyrogens may be important in the pathogenesis of the blunted febrile response to infection observed in the elderly. There is no evidence in humans that reducing a fever with antipyretic drugs increases the risk of morbidity and mortality if appropriate antimicrobial therapy is initiated. Fever in the elderly can result in discomfort, tachycardia, and other physiologic stresses that may be harmful, and these symptoms provide a rationale for antipyretic use (18). B. Baseline Temperatures and Definition of Fever in the Nursing Home The normal and febrile body temperature for older adults has been thoroughly reviewed recently (16). Baseline temperature and diurnal variation of temperature as measured by electronic thermometry was decreased in a nursing home population (29,30). Mean baseline morning rectal temperature was established to be 98.6 degrees Fahrenheit (F) (37 degrees centigrade [C]) in 22 residents in whom oral temperatures could not be easily obtained. The mean oral temperature of 85 additional residents was 97.4 degrees F (37.3 degrees C). Diurnal variation was only 0.6 degrees F (0.3 degrees C) for rectal temperatures and 0.4 degrees F (0.2 degrees C) for oral temperatures. In another study, 50 randomly selected nursing home residents had mean oral baseline temperature of 97.4 degrees F (36.3 degrees C) (29). A retrospective review found 69 infections in 26 of these residents, with the mean maximum temperature reaching 101.3 degrees F (38.5 degrees C). In nearly half these infections, the temperature did not reach 101 degrees F. Yet, a majority of these patients significantly increased their temperature over baseline by at least 2.4 degrees F (1.3 degrees C). Lowering the criterion for fever to 100 degrees F (37.8 degrees C) or higher raised the sensitivity to 70% for predicting infection with a specificity of 90%. These findings led to the recommendation by the Practice Guidelines Committee of the Infectious Diseases Society of America that a clinical evaluation be done for nursing home residents with a single oral temperature higher than 100 degrees F (37.8 degrees C) or persistent oral or rectal temperature higher than 99 degrees F (37.2 degrees C) or greater than 99.5 degrees F (37.5 degrees C), respectively. Two or more readings of more than 2 degrees F (1.1 degrees C) over baseline regardless of site of measurement should also stimulate an evaluation for infection (31). The chance of an infection is further increased if obvious symptoms and signs of infection exist or if there is any change in functional status accompanying the temperature changes (see Table 1). In some cases a significant decrease in temperature might also indicate a serious infection complicated by sepsis.

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C. Significance of Robust Fever Response and Fever of Unknown Origin (FUO) Infected elderly residents of LTCFs who mount a vigorous febrile response similar to younger adults, as defined by 101 degrees F orally (38.3 degrees C), can be expected to have a serious or life-threatening infection. This conclusion is extrapolated from a classic study of 1,200 ambulatory care patients (32) and two other confirmatory studies (33,34). In contrast to the young in whom these fevers were usually the result of benign viral infections, the elderly, especially the very old, usually suffered from a serious or life-threatening infection. Finally, infection is the leading etiology of FUO in the elderly, followed by connective tissue diseases such as temporal arteritis. A lesser number of cases are the result of malignancy (35–37). Many of these underlying conditions are treatable and, unless advanced directives preclude an extensive evaluation, an underlying cause for FUO in the older person should be sought.

IV. CONCLUSION The clinician must be familiar with all the manifestations of infections in the longterm care setting to minimize the impact of infectious diseases in this population. Preventive measures, rapid, aggressive diagnosis, and empiric therapy are essential to further reduce morbidity and mortality from infection. Fever, the hallmark of infection, may be absent or blunted in 20% to 30% of infections in the frail elderly. Alternatively, the presence of a vigorous fever in the older LTCF resident is more likely to be associated with a serious bacterial infection compared with a younger population, and requires a thorough and prompt evaluation.

REFERENCES 1.

2. 3. 4.

5.

Bradley SF. Infections and infection control in the long-term care setting. In: Yoshikawa TT, Norman DC (eds). Infectious Disease in the Aging. A Clinical Handbook. Totowa, Humana Press, 2001:245–256. Gleckman RA, Bradley PJ, Roth RM, Hibert DM. Bacteremic urosepsis: A phenomenon unique to elderly women. J Urol 1985; 133:174–175. Norman DC, Yoshikawa TT. Intraabdominal infection: Diagnosis and treatment in the elderly patient. Gerontology 1984; 30:327–338. Campbell BS, Wilson SE. Intraabdominal Infections. In: Yoshikawa TT, Norman DC (eds). Infectious Disease in the Aging. A Clinical Handbook. Totowa: Humana Press, 2001:91–98. Bentley DW. Bacterial pneumonia in the elderly: Clinical features, diagnosis, etiology and treatment. Gerontology 1984; 30:297–307.

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9. 10.

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12. 13. 14. 15. 16. 17.

18. 19. 20. 21. 22. 23. 24.

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Marrie TJ, Haldane EV, Faulkner RS, Durant H, Kwan C. Community-acquired pneumonia requiring hospitalization: Is it different in the elderly? J Am Geriatr Soc 1985; 33:671–680. Gleckman R, Hibert D: Afebrile bacteremia. A phenomenon in geriatric patients. JAMA 1982; 248:1478–1481. Finkelstein M, Petkun WM, Freedman ML, Antopol SC. Pneumococcal bacteremia in adults: Age-dependent differences in presentation and outcome. J Am Geriatr Soc 1983; 31:19–27. Terpenning MS, Buggy BO, Kauffman CA. Infective endocarditis: Clinical features in young and elderly patients. Am J Med 1987; 83:626–634. Werner GS, Schulz R, Fuchs JB, Andreas S, Prange H, Ruschewski W, Kreuzer H. Infective endocarditis in the elderly in the era of transesophageal echocardiography: Clinical features and prognosis compared with younger patients. Am J Med 1996; 100:90–97. Trivalle C, Chassagne P, Bouaniche M, Landrin I, Marie I, Kadri N, Menard JF, Lemeland JF, Doucet J, Bercoff E. Nosocomial febrile illness in the elderly: Frequency, causes, and risk factors. Arch Intern Med 1998; 158(14):1560–1565. Gorse GJ, Thrupp LD, Nudleman KL, Wyle FA, Hawkins B, Cesario TC. Bacterial meningitis in the elderly. Arch Intern Med 1984; 144:1603–1607. Potts FE, IV, Vukov LF: Utility of fever and leukocytosis in acute surgical abdomens in octogenarians and beyond. J Geront A Biol Sci Med Sci 1999; 54A(2):M55–M58. Yoshikawa TT, Norman DC: Fever in the elderly. Infect Med 1998; 15(10):704–706. Norman DC. Fever and aging. Infect Dis Clin Pract 1998; 7(8):387–390. Norman DC. Fever in the elderly. Clin Infect Dis 2000; 31:148–151. Weinstein MP, Murphy JR, Reller RB, Lichenstein KA. The clinical significance of positive blood cultures: A comprehensive analysis of 500 episodes of bacteremia and fungemia II: Clinical observations with special reference to factors influencing prognosis. Rev Infect Dis 1983; 5:54–70. Mackowiak, PA. Physiological rationale for suppression of fever. Clin Infect Dis 2000; 31(suppl 5):S185–S189. Kluger MJ, Ringler DM, Anver MR: Fever and survival. Science 1975; 188:166–168. Covert JB, Reynolds WM: Survival value of fever in fish. Nature 1977; 267:43–45. Netea MG, Kullberg BJ, Van der Meer JWM. Circulating cytokines as mediators of fever. Clin Infect Dis 2000; 31:S178–S184. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis 1999; 179(suppl 2): S294–S304. Norman DC, Yamamura RH, Yoshikawa TT. Fever response in old and young mice after injection of interleukin. J Gerontol 1988; 43:M80–M85. Miller D, Yoshikawa TT, Castle SC, Norman DC. Effect of age in fever response to recombinant tumor necrosis factor alpha in a murine model. J Gerontol 1991; 46: M176–M179. Miller DJ, Yoshikawa TT, Norman DC. Effect of age on fever response to recombinant interleukin-6 in a murine model. J Gerontol A Biol Sci Med Sci 1995; 50A: M276–M279. Plata-Salamán CR, Peloso E, Satinoff E. Interleukin-1-induced fever in young and old Long-Evans rats. Am J Physiol 1998; 275:R1633–R1638.

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Bradley SF, Vibhagool A, Kunkel SL, Kauffman CA. Monokine secretion in aging and protein malnutrition. J Leukocyte Biol 1989; 45:510–514. Scarpace PJ, Bender BS, Burst SE. The febrile response of E. coli peritonitis in senescent rats. Gerontologist 1990; 30:215A. Castle SC, Norman DC, Yeh M, Miller D, Yoshikawa TT. Fever response in elderly nursing home residents: Are the older truly colder? J Am Geriatr Soc 1991; 39: 853–857. Castle SC, Yeh M, Toledo S, Yoshikawa TT, Norman DC. Lowering the temperature criterion improves detection of infections in nursing home residents. Aging Immunol Infect Dis 1993; 4:67–76. Bentley DV, Bradley S, High K, Schoenbaum S, Taler, G, Yoshikawa TT. Practice guideline for evaluation of fever and infection in long-term care facilities. Clin Infect Dis 2000; 31:640–653. Keating MJ III, Klimek JJ, Levine DS, Kiernan FJ. Effect of aging on the clinical significance of fever in ambulatory adult patients. J Am Geriat Soc 1984; 32:282–287. Wasserman M, Levinstein M, Keller E, Lee S, Yoshikawa TT. Utility of fever, white blood cells, and differential count in predicting bacterial infections in the elderly. J Am Geriat Soc 1989; 37:534–547. Schoeinfeld CN, Hansen KN, Hexter DA, Stearns DA, Kelen GD. Fever in geriatric emergency patients: Clinical features associated with serious illness. Ann Emerg Med 1995; 26(1):18–24. Esposito AL, Gleckman RA. Fever of unknown origin in the elderly. J Am Geriatr Soc 1978; 26:498–505. Berland B, Gleckman RA. Fever of unknown origin in the elderly: A sequential approach to diagnosis. Postgrad Med 1992; 92:197–210. Knockaert DC, Vanneste LJ, Bobbaers HJ. Fever of unknown origin in elderly patients. J Am Geriatr Soc 1993; 41:1187–1192.

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32. 33.

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35. 36. 37.

7 Ethical Issues of Infectious Disease Interventions Elizabeth L. Cobbs Washington D.C. VA Medical Center, and George Washington University, Washington, D.C.

I. INTRODUCTION Long-term care facilities (LTCFs) provide care to dependent persons with a variety of needs and expectations and, in a shifting medical marketplace, ethical issues are part of the daily routine. In the wake of shortened hospital stays, the use of nursing homes for subacute post-hospital stays has surged. Short-term residents may receive rehabilitation services or continuing medical treatment for serious illnesses such as osteomyelitis. Improvement in function and health is the usual goal, and discharge to the community is often expected. The other larger group of residents living in LTCFs is composed of frailer individuals who are likely to reside in the LTCF through the end of life. The nursing home is their home. Their expectations for medical care are varied, as are their abilities to make decisions and express treatment preferences. A subset of those residents are near the end of life. In addition to their medical complexity, LTCF residents are at increased risk for infectious diseases because of physiological changes associated with aging, the impact of chronic conditions, and the effects of institutional living (1). Infection has been cited as the most frequent cause of transfer to the hospital (2), and hospital transfer is a frequent response to the medically ill resident in the LTCF, although practice varies. To serve this diverse group of residents, the LTCF is expected to provide timely and appropriate medical care, while at the same time offering a comfortable, personalized residence. The dual task of meeting the medical needs of many residents and providing a homelike environment that delivers a pleasing quality of life for dependent frail persons creates the setting for a number of ethical dilem79

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mas faced by LTCF practitioners. “The ethical issues in any care system reflect the nature of the care provided, the setting in which the care takes place, the capabilities of the care recipients, the commitments of the care providers, and the social and financial arrangements that society has created to structure and reimburse activities of caring” (3).

II. THE PLACE OF ETHICS IN LTCFs Knowledge of medical ethics helps physicians and other practitioners to do the right thing in the long-term care environment, where competition between medical and humanistic agendas are typical. Several ethical themes are integral to life in LTCFs. A. Autonomy Autonomy refers to self-determination without overbearing external influence, a prized attribute in American society. Autonomy becomes a ubiquitous ethical concern in the LTCF because all those who live in this setting do so because their ability to function independently has been compromised. Serving the needs of dependent residents within a medical model requires a reworking of the definition of autonomy. Perception and experience of autonomy are influenced by many factors, including culture. The Milwaukee Hmong community, for example, perceives dementia not as a chronic disease that robs a person of autonomy but as a natural part of the life cycle. Individuals suffering from dementia are cared for in their sons’ homes and rarely display difficult behaviors such as combativeness and wandering (4). Autonomy in an LTCF is most often expressed through a pattern of living rather than through discrete decisions (3). B. Beneficience and Nonmaleficience Beneficience refers to doing good, and in the practice of medicine this translates to doing the right thing for the patient. Defining the “right thing” has undergone a shift in recent years with increased understanding of the needs of the growing population of older adults living with chronic conditions (causing both physical and mental deficits) and significant self-care needs. Weighing the burdens and benefits of possible interventions has become standard practice in making treatment decisions for LTCF residents, because of the risks associated with virtually all treatment options. Closely related to beneficience is the admonition to do no harm, known as nonmaleficence. Nonmaleficence has taken on greater importance as the burdens of common treatment options, such as hospitalization, are recognized, and options for prompt and effective out-of-hospital treatments increase. The era

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recognizing residents’ rights in LTCFs came about after the 1987 passage of the Omnibus Budget Reconciliation Act, with perhaps the most noticeable result being a change of practice in the use of physical and chemical restraints. C. Fidelity Fidelity embraces trust and confidentially and is a fundamental principle underlying the doctor-patient relationship. The doctor-patient relationship remains fundamental to the care of residents in LTCFs; however, certain compromises to this relationship are inevitable because of the high frequency of cognitive impairment found among residents. Issues of trust pertain also to relationships with others on the interdisciplinary team (IDT) and often are important for residents to achieve a sense of control. D. Justice Justice refers to the equitable distribution of resources and treatment and is especially relevant when the interests of residents, staff, the institution, and families come into conflict with each other. Competing demands for staff attention and resources create the need for individuals and systems to negotiate settlements to conflicts so that the needs of residents and others in the LTCF community are most equitably served. E. Everyday Ethics The need for everyday ethical principles to guide practice in LTCFs is derived from the complexity of the organizations, their objectives, and their many participants. The nursing home environment seeks to blend two very different cultures: the autonomous, individually controlled home with the externally regulated, physician-directed structure of a medical institution. The requirement for physician orders to permit basic elements such as diet, activity level, or permission to self medicate sets an overarching framework of paternalism. Affirmation of self occurs with new expressions of autonomy manifested by the residents’ activities being consistent with their personal values and preferences. The LTCF must create systems that encourage consistent decisions by residents to maximize autonomy, despite disability and the institutional setting (3). At times competition exists between interests. The residents are the primary customers of the facility, yet LTCFs have been criticized for a lack of attention to the values and preferences of the individual resident. With limited staffing, residents may compete for staff time and attention. An acutely ill resident becomes the focus of attention, sometimes creating a shortage of staff time to attend to the needs of other residents. Decisions about whether to hospitalize a resident are in-

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fluenced by competing interests, including institutional financial incentives and staffing capacity, in addition to patient preferences. Conflicts may also occur in the interface between the optimum well-being of the residents and the needs and preferences of the staff. Conflict can also be found between staff and facility, and the facility and outside organizations. Families and significant others are important members of the LTCF community and contribute to the caregiving process. Families, however, may add to the conflict between competing interests. The facility needs a system of regular conflict resolution that effectively and consistently resolves conflicts between competing interests and values (3). The resident faces many obstacles to maintaining a self that is capable of autonomous action. Providing opportunities for choice and exertion of control over the environment and participation in the decision-making process have been shown to positively influence resident life. Communication and negotiation are means to achieve the best possible outcomes for the resident as well as the staff and the institution. Many daily infection control decisions have ethical dimensions that require choices between competing concerns or values. Common issues include whether to isolate residents colonized with resistant organisms, whether an ill healthcare worker should be allowed to work, and whether to investigate clusters of infections (5). Additional issues have to do with when to treat, what to treat, whether to hospitalize, how to communicate with residents and families, what to do when treatment attempts become burdensome and residents refuse, how to improve staff behaviors that protect resident safety and health, and when not to treat.

III. GOALS OF CARE The development of individualized goals of care for each resident is a process that creates the best mechanism to maximize autonomy, quality of life, and desirable medical outcomes. In the process of developing goals of care, a comprehensive biopsychosocial assessment is performed. This assessment provides a framework for the integration of disease factors with psychosocial factors and other resident characteristics. This assessment yields measures of resident functional capacity and points out where interventions to improve function and enhance independence might be placed. The values’ history, including information about the resident’s preferences, hopes, fears, basis for meaning, spirituality, and personal goals, is integrated with the comprehensive assessment. The physician and resident (or surrogate) aim to reach a shared understanding of the resident’s health status, care needs and preferences, options for future treatment interventions, and likely outcomes. From this assessment, a blueprint of goals and plans for care can be developed. In this way,

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Table 1 An Example of a Scheme to Prioritize Goals of Care Intensive care First priority

Prolong life

Second priority

Maintain physical and cognitive function

Third priority

Maximize comfort

Comprehensive care

Basic care

Palliative care

Comfort care only

Maintain physical and cognitive function Prolong life

Maintain physical and cognitive function Maximize comfort

Maximize comfort

Maximize comfort

Maximize comfort

Prolong life

Maintain physical and cognitive function Prolong life

Source: Adapted from Ref. 8.

residents of widely differing decisional capacity, health status, and personal preferences have deliberately articulated, personally generated (to the extent possible) plans for care to guide treatment decisions. The health values of the seriously ill vary considerably from person to person, and they cannot be easily predicted from the person’s current state of health. Mental health is an important factor in determining how patients evaluate their health (6). There is no substitute for involving the resident (or surrogate in the event of resident incapacity) in developing goals for care. Practitioners can expect considerable variation in preferences for care based on a variety of factors, including ethnicity (7). Many institutions are developing structured approaches to advance care planning, including prioritization of goals of care. One scheme is shown in Table 1 (8).

IV. THE DOCTOR-PATIENT RELATIONSHIP Over the last several decades, the paternalistic model of medical care in the United States has given way to an increased emphasis on patient autonomy. Residents of LTCFs typically have significant cognitive impairment, physical frailty, and chronic disease that will be with them for the rest of their lives. These residents are likely to benefit from the “enhanced autonomy” model in which an active exchange of ideas and negotiation takes place with the goal of achieving the best possible decision for the resident (9). In many cases, goals of care will be dis-

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cussed with surrogates speaking on behalf of residents who make known their preferences for healthcare interventions. The unequal balance of power in the doctor-patient relationship is exaggerated in the LTCF. Outside the confines of the LTCF, the doctor has an advantage in power by having knowledge of medicine and of the patient, whereas the patient has little knowledge of either the doctor or medicine. In the LTCF, the physician becomes even more powerful and controls many aspects of the resident’s life by writing orders. Choice of physicians is limited to a few staff doctors or others who are willing to be credentialed and to visit the LTCF. Access to the doctor is usually determined by institutional routine, where the nurses serve as gatekeepers of physician access. On this uneven playing field, physicians must find ways to build trust with their patients so that difficult decisions can be made with the greatest possible autonomy and beneficience. Resident rights, such as the right to be given information about proposed or potential treatments and alternatives and the right to refuse treatment, serve as safeguards to counterbalance enhanced physician power. Conflict between patient and doctor over treatment choices usually occur when they disagree about values and when trust is lacking (10). Agreement over the desirability of treatments depends on the ability of the physician and patient to negotiate to develop a shared understanding of the patient’s values and goals for care in the context of the medical treatment options. “. . . autonomy is not a zero-sum game but a complex network of relationship obligations, which can be negotiated in one way under certain circumstances and in another way when the situation changes” (11).

V. DECISIONAL CAPACITY “Rarely is incapacity absolute; even people with impaired capacity usually possess some ability to comprehend, to communicate, and to form and express a preference” (12). Enhancing autonomous decision-making has received considerable attention in recent years, particularly since the Patient Self Determination Act (PSDA) became effective in 1991. The PSDA is a federal statute that requires patients be informed of their right to participate in medical decision-making and to write advance directives. Assessment of decisional capacity is complex. Decisional capacity is decision specific and may vary over time. The resident with decisional capacity must demonstrate the ability to choose among various therapeutic goals, understand and communicate relevant information, and reasonably apply that information to decision-making in keeping with those goals. Substantial numbers of residents of LTCFs may have been excluded from participating in discussions about care preferences because of an inability to determine decisional capacity

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(13). Guidelines for determining decisional capacity are being developed and studied (12). When a resident is judged to lack decision-making capacity around a certain issue, the surrogate (durable power of attorney for healthcare decisions or next of kin) should be consulted to speak on behalf of the resident. A. Quality of Life Quality measures in LTCFs span several domains, including quality of life, quality of care, and residents’ rights. Quality of life is an important goal of care in the nursing home (14). Some evidence shows that overall quality of life has improved for men and women older than 85 living in LTCFs (15). Nursing home leaders and patient care advocates report the three most important components of quality of life items as: dignity, self-determination and participation, and accommodation of resident needs (16). Achievement of these is found in the fabric of nursing home life, especially in the choice and control that residents have over daily issues. Residents attach great importance to choice and control over matters such as bedtime, rising time, food, roommates, care routines, use of money, use of the telephone, trips out of the nursing home, and initiating contact with the physician (17). Measurement of quality of life of cognitively impaired residents may be difficult. Often even elderly persons with significant cognitive impairment can still answer questions about their quality of life (18). In addition, a surrogate often knows only a little about a resident’s satisfaction with care. Physicians and nurses appear to have limited insight into the health-related quality of life of nursing home residents and probably should not be used as proxies when resident-based assessments can be obtained (19). Physicians may be able to affect perceived quality of life by making themselves more accessible to residents for questions and by negotiating and communicating directly with residents about proposed interventions that require trips out of the nursing home (e.g., consultations, diagnostic studies). B. Advance Directives 1. Preferences for Treatment Advance directives are designed to preserve resident autonomy through future states of incapacity. Advance directives are written documents that reflect resident preferences for care, as articulated through developing goals of care and the general care plan. All residents (or their surrogates) should be provided with the opportunity to articulate advance directives. Most LTCFs offer printed educational materials and processes for recording advance directives. Nondepressed, nondemented residents of LTCFs generally exhibit stable preferences for treatment when asked about cardiopulmonary resuscitation, intravenous antibiotics, mechanical ventilation, and artificial nutrition. They distinguish clearly between

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time-limited and indefinite treatment plans. They generally favor receiving intravenous antibiotics and limited mechanical ventilation, but reject most other treatments (20). In advanced chronic illness when death is expected, residents of LTCFs may have advance directives that articulate primary goals of care around the achievement of comfort and dignity. Under such circumstances, residents (or their surrogates) may direct healthcare professionals to implement treatment interventions to manage symptoms (e.g., pain control, relief of dyspnea), but not to prolong life. In such cases, advance directives might call for no cardiopulmonary resuscitation, no ventilator use, no feeding tube, no hospitalization (unless uncomfortable symptoms cannot be controlled in the nursing home), no intravenous fluids, no antibiotic treatment, and no laboratory studies. 2. Designating a Healthcare Proxy Residents should be encouraged to designate a healthcare proxy, that is, someone to speak for them in the event they lose capacity to make healthcare decisions. The physician should communicate with the healthcare proxy (surrogate) when the resident cannot participate in decision-making. In this way, the autonomy of the resident is best preserved, despite the existence of cognitive or functional deficits that preclude personal participation in decision-making. In many cases, the next of kin will serve as the surrogate, but the physician should be aware of the legal standing of the surrogate, to be sure that the authority to speak on behalf of the resident is indeed delegated to the person acting as surrogate. Other kinds of healthcare proxy include durable power of attorney, guardian, and conservator. Differences in healthcare proxy completion rates across different ethnic groups appear to be related to reversible barriers such as lack of knowledge and the perceived irrelevance of advance directives (21). C. Decision to Hospitalize “Transfer rates vary widely among nursing facilities and over time . . . Nursing facilities differ in case mix, in the number of residents with advance directives, and in clinical care resources” (22). Decisions about whether to hospitalize residents with infectious problems arise frequently in LTCFs. Pneumonia is the leading cause of hospitalization among nursing home residents, with a mortality in some studies of 40% to 50% (23). In the past, acute care facilities and LTCFs have offered distinctly different types of health services; treatment capabilities currently overlap. Differences between acute and long-term care settings still potentially include numbers and types of practitioners, sources of financial reimbursement, and philosophy of approach to the management of chronic diseases (24). The desirability and appropriateness of transfers of LTCF residents to hospitals provokes debate because of concern about cost, but also because of adverse

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effects of hospitalization (25). Physically frail long-term residents are the most likely to be hospitalized, but they may also be the least likely to benefit from hospitalization (26). Iatrogenic complications and emotional trauma for residents and families have been cited as adverse effects of hospitalization. Advancing age, lower admission Mini-Mental State Examination scores, and lower preadmission instrumental activities of daily living functional characteristics are independent risk factors for functional decline during hospitalization of older persons (27). Treatment of pneumonia in the LTCF may produce better outcomes for some patients than if they were hospitalized (28). Many patient, institutional, and physician factors affect this decision. Goals of care and the institution’s capacity to provide appropriate diagnostic and treatment interventions in a timely fashion are of particular importance. The physician’s obligation is to determine the course that best serves the needs and goals of the resident. D. Right to Refuse Care Residents who have the capacity to make decisions about healthcare matters have the right to refuse care. A major reason patients refuse a recommended care intervention is that they misconstrue or misunderstand the recommendation. Because much communication in LTCFs is accomplished through the interdisciplinary care team, the physician’s response to a resident refusing care ought to include a personal visit under comfortable, private, unhurried circumstances to discuss the proposed treatment with the resident (or surrogate). If outright disagreement between resident and physician continues, this is likely because of a difference in values. The refusal of amputation of a gangrenous extremity is sometimes encountered in LTCFs. Some regard the prospect of amputation as a fate worse than death (29). It is often helpful to involve other members of the IDT to better understand the reasons for the refusal and to try to create alternative plans for care that would be acceptable to the resident and yield the best available outcomes from the physician’s perspective. E. Advanced Dementia Dementia is an important condition affecting more than half the residents of LTCFs. Although residents with dementia may live many years, the disease is not curable, is inexorably progressive, and eventually ends in death. Decisions about treatment in advanced dementia are best carried out through development of the goals of care, as described above. Surrogates often adjust the goals of care as the disease and the resident’s level of disability progress, when the burdens of treatment loom larger than the benefits. Surrogates and families often choose to shift the emphasis of care from a focus on reactive treatments for medical problems, such as pneumonia or urinary tract infection, to proactive interventions designed

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to enhance pleasure and quality of life, as in freedom from restraints. Guidelines to support decision-making about whether to treat or not treat pneumonia in demented psychogeriatric nursing home patients have proved useful in some settings (30). When the goals of care are totally focused on achieving comfort and death is expected, as in a patient with very advanced dementia, it is not uncommon for families and surrogates to forego treating with antibiotics. F. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Since the treatment advances of the mid 1990s, the outlook for those living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) has brightened considerably. Long-term care options will be increasingly needed for patients who do not fully respond to antiretroviral therapy or who have significant neuropsychiatric disease (31). The HIV/AIDS residents have a variety of reasons for needing long-term care, including the need for 24-hour nursing/medical supervision, completion of medical treatment, and end-of-life care. Issues pertaining to the need for advance care planning and palliative care are particularly important for HIV/AIDS residents.

VI. HEALTH PROMOTION Health promotion remains an important dimension of high-quality health care in LTCFs. Immunizations are a particular focus of effective health promotion and are safe for even frail residents. Influenza is an important cause of epidemic and endemic respiratory illness in LTCFs and results in considerable morbidity and mortality. The annual vaccination of residents and staff remains the most effective way to prevent influenza and its complications. However, vaccination rates have fallen short of public health targets. Facilities should develop resident and staff vaccination programs to improve the rate of vaccination (32). Pneumococcal vaccine and annual tuberculin skin testing are also recommended. Other health promotion activities, such as maintaining the highest level of mobility and function possible, are important in preventing deep venous thromboses, pressure ulcers, and other conditions associated with immobility.

VII.

ROLE OF THE IDT

Effective IDTs are essential to the provision of high-quality care in LTCFs and can alleviate many of the ethical dilemmas that characterize life in these institu-

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tions. The dominant providers in these facilities are nursing aides who render the majority of the direct care to residents. The ability of the nursing aide to recognize a change in the resident’s status and bring it to the attention of the medical practitioner permits the earliest possible identification of an infectious problem. This system of surveillance compensates for the atypical presentation that commonly characterizes illnesses of the frail elderly resident. Nurses view advocacy as a responsibility of their practice, where advocacy is rooted in the concept of individual rights (33). Social workers also practice an advocacy role, supporting three elements of autonomy: free action (supporting residents’ choices), decision-making (helping residents deliberate effectively), and continuity (maintaining a sense of self) (34). Geriatric nurse practitioners help to achieve optimal coordination of care and reduce emergency department and acute care utilization costs as well as overall costs for some managed care programs for LTCF residents (35). The key to effective IDT functioning is good communication that facilitates the flow of information to the team member who is best able to recognize its significance and respond appropriately.

VIII. INTERVENTIONS: BURDENS AND BENEFITS Diagnostic and treatment interventions bring benefits and burdens for the resident. Resident (or surrogate) decisions to accept or decline treatment may in part be determined by the perceived burdens of treatment interventions. Less burdensome options may exist. In-and-out bladder catheterization, for example, can be a frightening and uncomfortable procedure for a frail, elderly women. Investigators have demonstrated that urine specimens can be collected externally from incontinent female LTCF residents (36). Intravenous antibiotic therapy of a resident with dementia who pulls out the intravenous line on a daily basis brings the burden of repeated needlesticks and perhaps physical restraints. For an extremely debilitated resident, even transportation for a diagnostic test may be exceedingly burdensome because of discomfort from prolonged periods of waiting and riding in a bumpy wheelchair van, fear of uncertainty and a strange environment, and risk of falls from caregivers unfamiliar with the resident’s level of functional capacity. Practitioners often can devise alternative plans that minimize treatment burdens, sometimes with help from the IDT and outside consultants to assure resident comfort, control, and dignity. Consent should be sought from the resident or surrogate before embarking on a burdensome course of diagnostic testing or treatment intervention. Trials of treatment interventions may be helpful when there is ambivalence about declining or accepting an intervention. A time-limited trial (e.g., of tube feeding or hemodialysis) with the option to continue or discontinue treatment after seeing how well it is tolerated may be helpful.

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IX. END-OF-LIFE CARE Long-term care facilities will play an increasingly important role in the care of people nearing the end of life. In 1993, 20% of U.S. deaths occurred in nursing homes. By 2040 this proportion is expected to rise to 40% (37). Improving care near the end of life for LTCF residents goes beyond advance care planning and advance directives. Effective symptom management, maximization of functional capacity, and assistance with issues pertaining to life closure are additional important services that must be offered consistently as part of a system that achieves good care for those nearing the end of life. Over the past few years, the healthcare profession has recognized the need to improve the quality of care for people near the end of life, but consensus about how to accomplish this has not yet been achieved. Those living with serious chronic illness near the end of life are likely to follow one of three trajectories: (1) a relatively brief period of severe functional decline at the end of life (typical of cancer); (2) long-term disability with periodic exacerbations and unpredictable timing of death (as in congestive heart failure and chronic obstructive pulmonary disease); or (3) slow dwindling course to death with significant self-care deficits (usually from extreme frailty or dementia). These trajectories shed light on possible care systems that would serve residents’ needs better (38). A number of studies have identified effective communication and pain management as shortcomings in the care of dying persons. Bereaved family members are generally satisfied with life-sustaining treatment decisions but voice concerns about failures in communication and pain control. Nursing home care has received the smallest proportion of positive comments, including mention of poorly trained or inattentive staff and remoteness of physicians. Families recommend that care could be improved through better communication, greater access to physicians’ time, and better pain management (39). LTCF residents near the end of life are focused on the quality of living rather than dying. They have concerns with day-to-day living, difficulty chewing and swallowing, better pain relief and sense of control, strengthening relationships with loved ones, importance of religious activities, giving care to others, and appreciation of respectful and prompt care (40,41).

X. CONTACT ISOLATION Although prevalence of antibiotic-resistant bacteria in LTCFs has been described, managing residents colonized with antibiotic-resistant organisms has come to represent a significant challenge for practitioners in these settings (42). Contact isolation of a resident colonized with a resistant organism represents an affront to that resident’s freedom created by the obligation to protect the rights

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of other residents to be free from harm, particularly those in subacute settings. Adverse effects of contact isolation include less frequent care and negative psychological consequences (43). There are likely to be significant differences between different types of LTCFs (e.g., the Veterans Affairs nursing home care unit population vs community nursing home population) (44). More needs to be learned about the risk to residents and how to develop antibiotic resistance precautions that are effective, inexpensive, and achievable in LTCFs. The IDT may address the psychological problems that the isolated resident experiences and develop strategies to avoid unnecessary complications of isolation procedures. For example, the IDT might permit a resident to wash his face and hands, don a clean gown, and walk in the halls to physical therapy at the end of the day (see chapters in Part III and Chapter 8).

XI. COST CONCERNS The varied arrangements for financing care in the LTCF create a variety of ethical dilemmas for facilities and practitioners. Every treatment option has a cost that must be factored into the process of clinical decision-making. Financial incentives to accept residents with complex medical needs into the facility exist with some payors but not with others. Some payors encourage transfer of the acutely ill resident to the hospital and others reward the LTCF and the practitioner for treating the resident in the LTCF. The high cost of antibiotics such as vancomycin may create significant dilemmas. In some cases, for cost reasons, residents may not be able to return to the LTCFs they consider home. Significant variation exists in prescribing and the cost of antimicrobials among LTCFs (45), and formularies and guidelines are being developed to standardize prescribing practices.

XII.

INFECTION CONTROL PRACTICES BY STAFF

The LTCF staff plays an important role in infection control through the use of precautions and routines (see Chapters 8 and 9). From an ethics standpoint, these are measures that carry little risk or burden to the staff and are effective in maintaining infection control. Hand washing is perhaps the most obvious low risk strategy, yet marked shortcomings in the use of hand washing and gloves continue to exist in LTCFs (46). Hand-washing practices vary considerably across hospital wards and type of worker, and lack of good hand washing appears to be associated with understaffing (47). A common ethical dilemma is the question of whether a sick employee should be working. Prohibiting a staff member with a contagious illness from working with residents follows from the ethical concept of utility that strives to

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maximize good outcomes while minimizing harm. Institutional staffing shortfalls or the staff member’s reluctance to take a sick day may compete with this value. Another ethical quandary is presented when staff members fail to get influenza vaccines. The medical director should work with infection control professional and other members of the IDT to create an institutional ethic of good infection control practices, supported by strong educational programs for staff and effective employee health services.

XIII. ROLE OF THE MEDICAL DIRECTOR The medical director bears responsibility for the overall quality of care provided in the LTCF. Along with the director of nursing and the facility administrator, the medical director should develop a basic ethics policy framework (48). Effective implementation of ethics policies requires a shared vision by the leadership, adequate support for the process, and explicit guidelines for the staff and practitioners, residents, and families. A mechanism to resolve disputes should be developed. Ethics committees have fulfilled this role in some facilities. Measuring outcomes that reflect quality of care in LTCFs is an important dimension of quality management for which the medical director has oversight. The Minimum Data Set (MDS) has provided some quality indicators for LTCFs (such as pressure ulcers, use of psychotropic medications, falls) but other measures need to be developed. Needs for pain relief and spiritual support are not routinely addressed by the MDS and Resident Assessment Protocol (RAP) triggers. Indicators are likely to vary for different subsets of LTCF residents. Key indicators for the care of terminally ill residents include communication of advance directives, attention to pain management, and relief of dyspnea (49). For residents who desire antibiotic treatment for infectious diseases, early empiric antibiotic therapy has an important impact on the outcomes of pneumonia (50); thus, percent of residents who received antibiotics within 4 hours of diagnosis of infection might be a worthwhile quality indicator.

XIV. RESEARCH ISSUES IN INFECTION CONTROL Research is an important avenue in improving treatment and preventing infectious disease in LTCF residents. There are multiple facets of ethical obligation in the LTCF research endeavor. Guidelines for ethical investigations have been put forth (51). The Ethics Committee of the American Geriatrics Society has outlined guidelines for appropriateness of the informed consent process for patients with dementia who are research subjects (52). The interest of the individual resident may be at times in opposition to the interests of the population within the facility.

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A mandate to do no harm and protect confidentiality exists for both the individual and the population. However, the individual resident seeks privacy and autonomy, whereas the concern of the population lies in investigating, reporting, and achieving justice. Infection control activities ought to investigate clusters of adverse outcomes, identify and implement cost-effective interventions, safeguard the health of residents and staff, measure the efficacy of interventions, and avoid conflicts of interest around recommendations of products and equipment. Residents who become subjects for research (or their surrogates) must provide informed consent, and they must be assured that their welfare, privacy, and confidentiality will be protected. Staff members should be protected from harm (taking precedence over staff freedom)(5). Although basic standards of research ethics are not usually reported in nursing home research, the instructions of a journal for the author or other features of peer review can affect the quality of reporting research ethics (53). Well-written policies on the protection of cognitively impaired research subjects is an important way that research institutions can demonstrate that serious attention is paid to the rights and welfare of cognitively impaired residents (54).

XV. FUTURE Long-term care facilities are likely to continue to be places where functionally dependent persons receive medical and personal care, either episodically or as a final place of residence toward the end of life. The ethical issues interwoven into

Table 2 Promises to Those with Advanced Stages of Serious Illness 1. GOOD MEDICAL TREATMENT—You will have the best of medical treatment, aiming to prevent exacerbation, improve function and survival, and ensure comfort. 2. NEVER OVERWHELMED BY SYMPTOMS—You will never have to endure overwhelming pain, shortness of breath, or other symptoms. 3. CONTINUITY, COORDINATION, AND COMPREHENSIVENESS—Your care will be continuous, comprehensive, and coordinated. 4. WELL PREPARED, NO SURPRISES—You and your family will be prepared for everything that is likely to happen in the course of your illness. 5. CUSTOMIZED CARE, REFLECTING YOUR PREFERENCES—Your wishes will be sought and respected, and followed whenever possible. 6. USE OF PATIENT AND FAMILY RESOURCES (financial, emotional, and practical)—We will help you and your family consider your personal and financial resources, and we will respect your choices about the use of those resources. 7. MAKE THE BEST OF EVERY DAY—We will do all we can to see that you and your family have the opportunity to make the best of every day. Source: Adapted from Ref. 55.

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this environment are powerful determinants of the outcomes that LTCF residents experience. An articulation of a vision for the future guides practitioners and others to achieve the best possible quality of life and care for LTCF residents (Table 2) (55).

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Garibaldi RA. Residential care and the elderly: The burden of infection. J Hosp Infex 1999; 43 Suppl:S9–S18. Yoshikawa TT, Norman DC. Approach to fever and infection in the nursing home. J Am Geriatr Soc 1996; 44:74–82. Dubler NN. Reflections on some ethical issues in long-term care. In: Binstock RH, Cluff LE, Von Mering O (eds). The Future of Long-Term Care: Social and Policy Issues. Baltimore, Johns Hopkins Press, 1996:238–251. Olson MD. “The heart still beats, but the brain doesn’t answer.” Perception and experience of old-age dementia in the Milwaukee Hmong community. Theoretical Med Bioethics 1999; 20(1):85–95. Herwaldt LA. Ethical aspects of infection control. Infect Control Hosp Epidemiol 1996; 17:108–113. Tsevat J, Cook F, Green ML, Matchar DB, Dawson NV, Broste SK, Wu AW, Phillips RS, Oye RK, Goldman L, for the SUPPORT Investigators. Health values of the seriously ill. Ann Intern Med 1995; 122:514–520. Vaughn G, Kiyasu E, McCormick WC. Advance directive preferences among subpopulations of Asian nursing home residents in the Pacific Northwest. J Am Geriatr Soc 2000; 48:554–557. Gillick M, Berkman S, Cullen L. A patient-centered approach to advance medical planning in the nursing home. J Am Geriatr Soc 1999; 47:227–230. Quill TE, Brody H. Physician recommendations and patient autonomy: Finding a balance between physician power and patient choice. Ann Intern Med 1996; 125: 763–769. Lantos JD. Futility assessments and the doctor-patient relationship. J Am Geriatr Soc 1994; 42:868–870. Helft PR, Siegler M, Lantos J. The rise and fall of the futility movement. N Eng J Med 2000; 343:293–296. Mezey M, Teresi J, Ramsey G, Mitty E, Bobrowitz T. Decision-making capacity to execute a health care proxy: Development and testing of guidelines. J Am Geriatr Soc 2000; 48:179–187. Bradley E, Walker L, Blechner B, Wetle T. Assessing capacity to participate in discussions of advance directives in nursing homes: Findings from a study of the Patient Self Determination Act. J Am Geriatr Soc 1997; 45:79–83. Ouslander JG, Osterweil D. Physician evaluation and management of nursing home residents. Ann Intern Med 1994; 121:584–592. Liao Y, McGee DL, Cao G, Cooper RS. Quality of the last year of life of older adults: 1986 vs 1993. JAMA 2000; 283:512–518. Harrington C, Mullan J, Woodruff LC, Burger SG, Carrillo H, Bedney B. Stakehold-

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porting of research ethics in publications of nursing home research? J Am Geriatr Soc 1999; 47:76–81. 54. Cahill M, Wichman A. Research involving persons with cognitive impairments: Results of a survey of Alzheimer disease research centers in the United States. Alzheimer Dis Assoc Disorders 2000; 14:20–27. 55. Lynn J, Schuster JL, Kabcenell A. Improving Care for the End of Life: A Sourcebook for Health Care Managers and Clinicians. New York, Oxford University Press, 2000.

8 Nursing Management of Infections Donna L. Barton Lake Eustis Care Center, Eustis, Florida

Janet D. Register Leesburg Regional Medical Center, Leesburg, Florida

I. INTRODUCTION When caring for residents in a long term-care facility (LTCF), infections are frequently encountered. Each facility must have an infection control program as mandated by Federal regulation (1). This program is designed to investigate, control, and prevent infections in the facility; decide what procedures, such as isolation, should be applied to an individual resident; and maintain a record of incidents and corrective actions related to infections. In the August 1991 Journal of Infection Control, the Association for Practitioners in Infection Control (APIC; now called Association for Professionals in Infection Control and Epidemiology), published “APIC guideline for infection prevention and control in the long-term care facility” (2). This article assists in establishing an infection control program for LTCFs. It provides information on how to establish an effective surveillance program. Total surveillance is recommended for all residents for whom antibiotic therapy is prescribed while residing in LTCFs. This includes reviewing the medical history of residents admitted to the facility with antibiotic orders (community-acquired infections), as well as those who developed infections and were given antibiotic therapy while residing in an LTCF (nosocomial infections).

II. SURVEILLANCE The purpose of surveillance is to identify trends that may be occurring so that a potential outbreak can be avoided and to determine educational needs for the en99

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tire staff caring for the residents. An important part of surveillance is to establish criteria for identifying infections of various body systems. In February 1991, the American Journal of Infection Control published an article entitled “Definition of infections for surveillance in long-term care facilities,” which can serve as a reference in establishing these criteria (3). Contributors to this informative article included representatives from APIC, Centers for Disease Control and Prevention (CDC), and many teaching hospitals throughout the United States and Canada. Using this as a guide and working with the facility medical director, criteria can be formulated for those symptoms that best signal an infection (see the appendixes of this book for summary of these criteria). A reliable method to help the nurse identify the presence of infection in residents is the basic “nursing process” of assessment, diagnosis, planning, implementation, and evaluation (4) (Table 1). All items of the nursing process should be reviewed by the nurse before the physician is given the assessment findings of a resident suspected of having an infection. The purpose of the nursing process is to compile an accurate, concise, comprehensive resident assessment to present to the physician. Important information includes the following: • • • • • •

Current physician orders The most recent physician progress notes The resident’s current medications Vital signs, if applicable Any abnormal laboratory or radiology finding available A brief history of the resident’s current problem

Table 1 Basic Nursing Process Assessment

Diagnosis Planning

Implementation Evaluation

Use criteria adopted for presence of infection in specific body system. Collect data through interview with resident for subjective and objective complaints, review of history, medical record, and physical examination. Compile the assessment findings and laboratory results in a systematic method for presentation to physician for diagnosis. Obtain physician orders, list needed comfort measures, identify appropriate room placement for containment, identify necessary isolation precautions as indicated by symptoms and physician diagnosis. (Care Planning Process for significant change.) Carry out individualized plan of care as established. Follow-up on outcomes of implementation of plan of care. If symptoms continue, return to assessment, presentation of information to physician for diagnosis, alteration of Care Plan, implementation of new Care Plan, and evaluation of outcomes.

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The nurse should keep the resident’s chart available for writing any new physician orders or for access to any additional information.

III. IDENTIFICATION OF INFECTIONS A. Clinical Manifestations Once criteria for identifying nosocomial infections have been formulated by the facility’s infection control committee, it is important to remember that not all LTCF residents with infection will present with these symptoms. Atypical clinical manifestations are not unusual in the elderly. Often a temperature elevation is thought to be the first sign of an infection. In the elderly, however, fever may be absent or the body temperature may be below normal (see Chapter 6). And an early sign of pneumonia may only be tachypnea (5–7). There is a need to profile each individual resident as to past symptoms and signs of a specific infectious process. There are instances in which the only evidence of an infectious process is a change in normal behavior patterns, a change in mentation, a decrease in the resident’s normal activity level, or poor fluid and food intake. Some residents may have symptoms compatible with an infection, but due to dementia, aphasia, or nonresponsiveness, they are unable to communicate their presence. Every LTCF has at least one resident who has been labeled a “chronic complainer.” Regardless of past experience with this type of resident, each new complaint necessitates a thorough nursing assessment and physician notification, if indicated. B. Diagnostic Specimens and Microbiology The physician may ask for a specimen to be obtained for culture and sensitivity. Nurses need to be trained in the proper technique of obtaining specimens as indicated by the receiving laboratory. Nurses will also review the findings in the culture and sensitivity reports for communication to the physician. If no organism was found and the physician has prescribed an antibiotic, it is imperative for the nurse to notify the physician of the culture results. If an organism is found, the sensitivity report will identify whether the antibiotic ordered for treatment is effective or if the organism is resistant to the drug. If the infecting organism is resistant, the nurse must relay this information to the physician, along with a list of antibiotics to which the organism is sensitive. Antibiotic use must be closely monitored for its appropriateness to assist in decreasing the possibility of drug-resistant pathogens. C. Communication The identification of infections is a team effort. All staff must be involved: nurses, nursing assistants, therapists, environmental, dietary, and any other facility staff.

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Family members, visitors, and volunteers who come in contact with the resident routinely can also identify a change in that resident and provide information for nurses. It is important to establish lines of communication with all team members, families, visitors, and volunteers. Most frequently, these individuals will communicate their concerns to the nurse in charge of the resident’s care. The nurse must listen and be aware that a potential problem may exist that requires further resident assessment. It is particularly vital to investigate the concerns of nursing assistants regarding residents for whom they are caring. Nursing assistants are the direct caregivers who spend the most time with the residents and will most often be first to identify changes in the resident’s behavior. However, because their medical education is limited, they do not always have the terminology to describe their findings, and nursing follow-up of their observations is often lacking.

IV. PREVENTING INFECTIONS Knowing how infections spread is the first step in preventing their spread to staff members or other residents. The CDC recently published its Guidelines for Isolation Precautions in Hospitals (8). The categories for isolation precautions are standard, droplet, airborne, and contact. A. Standard Precautions Standard precautions combines the features of universal precautions and body substance isolation. It applies these precautions to all persons receiving care in any type of medical establishment, regardless of diagnosis or presumed infection status. Standard precautions apply to blood and all body fluids; secretion and excretions (except sweat), regardless of whether these fluids contain visible blood; nonintact skin; and mucous membranes. 1. Hand Washing The practice of standard precautions first addresses the importance of hand washing. A 15-second hand washing will be performed (9). • After touching blood, body fluids, secretions, excretions, nonintact skin, mucous membranes, contaminated items • Upon reporting to work at the start of the shift • Before and after each resident contact (it may be necessary to wash hands between tasks and procedures on the same resident to prevent cross-contamination of different body sites) • After using the restroom

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Before handling food Before and after eating or smoking Before and after handling patient care items Before and after glove usage Before leaving work area to go home After blowing or wiping one’s nose

Hand washing is to be performed at these times regardless of whether gloves are worn. With the increased encouragement of activities in LTCFs, residents are frequently found out of their room and in communal areas participating in the activities offered. With this increased mobility, residents themselves may be a source of infection to other residents. Just as hand washing is the key factor in preventing the spread of infection from the hands of the healthcare worker, so is frequent hand washing by the residents a deterrent in spreading infection to other residents (10). 2. Personal Protective Equipment (PPE) a. Gloves: These should be worn (clean, intact, nonsterile gloves are adequate) whenever the employee comes in contact with: • Moist body substances (e.g., blood, body fluids, secretions, and excretions) • Mucous membranes (mouth, nose, eyes, genitals, and rectum) (Put on clean gloves just before touching mucous membranes and instilling eye drops.) (11) • Nonintact skin (Put on clean gloves just before touching nonintact skin.) • Any resident care items that may be contaminated with moist body substances (e.g., bedpans, urinals, linens) Remove gloves promptly after use and wash hands before touching noncontaminated items, environmental surfaces, and before going to another resident. This helps to prevent transferring microorganisms to other residents or the environment. Gloves should be removed and hands washed before leaving a resident’s room. b. Gown: Wear a clean, nonsterile gown to protect skin and to prevent contamination of clothing during resident-care activities that are likely to generate splashes or sprays of blood, body fluids, secretions, or excretions. Remove a soiled gown promptly and wash hands to avoid transfer of microorganisms to other residents or the environment. c. Goggles, face shields, and masks: Wear these items to protect mucous membranes of the eyes, nose, and mouth during resident care activities that are likely to generate splashes or sprays of blood, body fluids, se-

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cretions, and excretions (e.g., emptying Foley bags, during resident suctioning, emptying suction canisters). d. Masks: These will be worn by staff members when a resident has an undiagnosed cough. This protects the healthcare worker who may be susceptible to an undiagnosed airborne disease carried by the resident. e. Resident care equipment: Handle all soiled resident-care equipment in a manner that prevents exposure to skin, mucous membranes, clothing, other residents, and the environment. • Reusable equipment must be cleaned and reprocessed appropriately before use by another resident, (e.g., intravenous poles, walkers, wheelchairs). • Ensure that single-use items are discarded properly. f. Linen: Handle, transport, and process used linen in a manner that prevents skin and mucous membrane exposures and contamination of clothing. Proper handling of linen will avoid transfer of microorganisms to other residents and the environment. 3. Occupational Health and Bloodborne Pathogens • Use safety devices, needleless systems, and procedures that help to minimize needlesticks and sharps injuries (e.g., never recap, bend, or break needles). • Place used disposable syringes, needles, scalpel blades, razor blades, and other sharp items in appropriate puncture-resistant containers. These containers should be located as close as practical to the area in which the items were used. The containers should be changed when two-thirds to three-quarters full. • Use care in handling sharp instruments after use, including razor blades. • Use mouthpieces, resuscitation bags, or other ventilation devices as an alternative to mouth-to-mouth resuscitation. B. Airborne Precautions In addition to standard precautions, use airborne precautions for residents known or suspected of being infected with microorganisms transmitted by airborne droplet nuclei (small-particle residue [5 microns or smaller in size] of evaporated droplets containing microorganisms that remain suspended in the air and can be dispersed widely by air currents within a room or over long distances). Airborne precautions are practiced to protect staff members, as well as any individual entering the precaution room. These precautions should be used for all residents diagnosed with or suspected of having active tuberculosis (TB), measles (rubeola), chickenpox (varicella), or herpes zoster.

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1. Resident Placement Residents should be placed in an isolation room. The room should: • have monitored negative air pressure in relation to the surrounding areas • have 6 to 12 air changes per hour • have appropriate discharge of air outdoors or monitored high-efficiency filtration of room air before the air is circulated to other areas in the facility • have the door closed at all times If there is no negative air pressure room in the facility, it will be necessary to transfer the resident to a facility that has appropriate accomodations. After the resident has been taking antituberculosis medications for at least 10 days, there is a marked improvement in symptoms, and the sputum smears are negative, the patient is no longer considered communicable and may return to the LTCF. (Note: criteria for proven cases of TB to be allowed to return to home or LTCF may vary from state to state). To maintain confidentiality, post a sign outside the room advising anyone preparing to enter the room to report to the nurses’ station. 2. Respiratory Protection • A particulate respirator mask, having the capacity to filter to 5 microns or less, should be worn by all employees and visitors entering the room of a resident with known or suspected TB or other airborne infections. • Employees who have not had measles or chickenpox, or been immunized for these infections, should not enter the room of residents with these infections, if other immune caregivers are available. • Persons immune to measles or chickenpox need not wear respiratory protection when caring for a resident with these infections. 3. Resident Transport Limit the transport of the resident from the room to essential purposes only. • Have diagnostic tests and procedures done in resident’s room rather than transporting the resident to other departments, when possible. • When resident must be transported out of the room to other departments, the resident is to wear a mask and the receiving department is to be alerted to the resident being on airborne precautions. 4. Education • Educate the resident and alleviate resident concerns about airborne precautions.

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• Inform resident to cover mouth and use tissues when coughing or sneezing, and teach the resident proper disposal of used tissues. • Educate visitors on the proper use of masks. • Keep employee and visitor traffic to a minimum. The termination of airborne precautions in a diagnosed or suspected TB case is permitted if: • TB has been excluded by smear and culture • The criteria for noncommunicability of an active TB case are met (see earlier discussion) • Resident is discharged home. C. Droplet Precautions In addition to standard precautions, use droplet precautions for a resident known to be or suspected of being infected with microorganisms transmitted by droplets (large particle droplets [larger than 5 microns in size] that can be generated by the resident during coughing, sneezing, talking, or during the performance of procedures). Droplet precautions are used to protect the staff, other residents, and families from infections transmitted by the droplet route. Droplet precautions should be instituted for all diagnosed or suspected cases of infections transmitted by droplets, for example, pertussis, diphtheria, Haemophilus influenzae, among others. 1. Resident Placement • All residents requiring droplet precautions will be admitted to a private room. • If a private room is not available, place the resident in a room with a resident who has active infection with the same microorganism but with no other infection (cohorting). • A notice will be placed outside the room requesting that everyone report to the nurses’ station before entering the room. 2. Mask In addition to standard precautions, all staff must wear a mask when working within 3 feet of the resident. 3. Resident Transport Transport the resident from the room only for essential purposes. • Whenever possible, have diagnostic tests and procedures done in resident’s room rather than transporting the resident to other departments.

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• When resident must be transported out of the room to other areas, the resident is to wear a mask to minimize dispersal of droplets. The receiving department should be notified of the droplet precautions. 4. Education • Educate the resident and alleviate resident’s concerns about droplet precautions. • Inform resident to cover mouth and use tissues when coughing or sneezing; teach the resident the proper disposal of used tissues. D. Contact Precautions In addition to standard precautions, use contact precautions for a specified resident known to be or suspected of being infected or colonized with important microorganisms that can be transmitted by direct contact with the resident (hand, or skin-to-skin contact that occurs when performing resident-care activities that require touching the resident’s dry skin) or indirect contact (touching) with environmental surfaces or resident care items in the resident’s environment. 1. Resident Placement • All residents requiring contact precautions will be admitted to a private room. • Place a resident who contaminates the environment or who does not (or cannot be expected to) assist in maintaining appropriate hygiene or environmental control in a private room. • When a private room is not available, place the resident in a room with a patient who has active infection with the same microorganism, but with no other infection (cohorting). • When a private room is not available and cohorting is not achievable, consider the epidemiology of the microorganism and the relative risk to the other resident(s) occupying the same room when determining placement. 2. Gloves and Hand Washing • Wear gloves as outlined under standard precautions. • While providing care for a patient, change gloves after having contact with infective material that may contain high concentrations of microorganisms (e.g., fecal material and wound drainage). • Remove gloves before leaving the resident’s environment and wash hands immediately with an antimicrobial agent or a waterless antiseptic agent.

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• After glove removal and hand washing, ensure that hands do not touch potentially contaminated environmental surfaces or items in the resident’s room to avoid transfer of microorganisms to other residents or the environment. 3. Gown • Wear a clean, nonsterile gown when entering the room if you anticipate that your clothing will have substantial contact with the resident, environmental surfaces, or items in the resident’s room. If the resident is incontinent or has diarrhea, an ileostomy, a colostomy, or wound drainage not contained by a dressing, a gown should be used to protect clothing. • Remove the gown before leaving the resident’s room and discard. • After gown removal, ensure that clothing does not contact potentially contaminated environmental surfaces to avoid transfer of microorganisms to other residents or the environment. 4. Patient Transport • Limit transport of the resident from the room to essential purposes only. • If the resident is transported out of the room, ensure that precautions are maintained to minimize the risk of transmission of microorganisms to other residents and contamination of environmental surfaces or equipment. Notify the receiving department that the resident is on contact precautions. 5. Patient Care Equipment • When possible, dedicate the use of noncritical resident-care equipment to a single resident (or cohort residents infected or colonized with the same pathogen) to avoid sharing equipment with noninfected residents. • Equipment dedicated to a single resident for use during contact precautions that will not be discarded is to be disinfected before being used by another resident. • Handle, transport, and process used linen in a manner that will not contaminate clothing and that avoids transfer of microorganisms to other residents or the environment. E. Antibiotic-Resistant Microorganisms Today, residents are becoming infected with antibiotic-resistant microorganisms more frequently than ever before. In LTCFs, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci are two of the most important resistant pathogens encountered. Extensive discussions on these organisms are found elsewhere in this book (see Chapters 22 and 23).

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Because of the scarcity of private rooms, criteria must be developed for the optimum selection of appropriate room placement and roommates for the residents diagnosed with infections caused by these resistant microorganisms. 1. Definitions Colonized. A resident is culture positive for the organism but exhibits no symptoms or signs of infection. Infected. A resident is culture positive for the organism and exhibits symptoms and signs of infection (e.g., purulent drainage from a wound, elevated temperature, productive cough, urinary frequency with pain or burning). Contained. • Wound. A draining wound is covered by an absorbent dressing that contains the wound drainage • Urinary. The resident has a Foley catheter or is continent. • Respiratory. The resident is competent to cover his mouth with tissues when coughing or sneezing and disposes tissues in a plastic bag. Uncontained. • Wound. Drainage from a wound is too profuse to be contained by a covering dressing. • Urinary. The resident is consistently incontinent of urine. • Respiratory. The resident is confused and consistently coughs, sneezes, and expectorates without using tissues. Resident’s culture status. • It is known that the resident’s cultures are negative for resistant microorganisms. • It is known that the resident’s cultures are positive for resistant microorganisms and the resident has an active infection. • It is known that the resident’s cultures are positive for resistant microorganisms, but the resident is exhibiting no symptoms or signs of active infection (colonized). • It is known that the resident is culture-negative at this time but has had a positive multiresistant microorganism culture in the past • It is NOT known if the resident has now or has had in the past, a positive culture for a multiresistant microorganism. 2. Risk for Acquiring an Infection with a Resistant Microorganism If a resident falls into any of the categories below, he or she is a greater risk for acquiring a colonization or infection with a resistant microorganism.

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• • • • •

Bed/chair confined Poor functional status Urinary incontinence (males) Open wounds or pressure ulcers Invasive devices present (e.g., Foley catheter, urostomy, colostomy, feeding tubes, tracheostomy, intravenous lines) • Frequent (or is currently on) antibiotic therapy • Prior infection or colonization with a resistant microorganism 3. Room Definition • Private. A single-bed room or a semiprivate room with no other resident. • Cohort. Placing a resident who is infected in a room with a resident who is infected with the same organism but with no other infectious organism. A colonized resident may also be placed in a room with another resident who is colonized with the same organism.

Table 2 Guidelines for Room Placement of Residents with Antibiotic-Resistant Microorganisms Room type: new admission

With a resident at low risk

Private room

Cohorting*

Resident culture negative

Yes

Resident culture positive for infection Resident culture positive, no infection, colonized Resident culture negative now, culture positive in the past

Yes

Yes, if new resident has been assessed as a low risk Yes

Yes

Yes

Yes

Yes, if new resident is now assessed as a low risk

Yes

Resident culture status unknown

Yes

Yes, if new resident has been assessed as a low risk

Yes

Yes

Yes, if no other placement is available Yes

With a resident at high risk Yes, if new resident has been assessed as a low risk No

No

Yes, when no other placement is available and resident is assessed as a low risk Yes, if new resident has been assessed as a low risk

* Residents, each colonized or infected with a different resistant microorganism, for example, methicillinresistant Staphylococcus aureus and vancomycin-resistant enterococci, respectively, should never be cohorted.

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• A room with a resident at low risk for acquiring an infection with a resistant microorganism. • A resident who has never had colonization from a resistant microorganism. • A resident who has no invasive devices present. • A resident who is not confined to bed or wheelchair. • A resident who has no incisions or open wound. • A room with a resident with high risk for acquiring an infection from a resistant microorganism (see earlier discussion). Guidelines for room placement are described in Table 2. The benefits of isolating residents should always be weighed against the potential adverse effects on psychosocial status and quality of life.

V. EDUCATION A. Infection Control Professional Long-term care facilities should make available educational opportunities to expand knowledge in infection control practices for the staff member designated to perform the duties of infection control professional (ICP). The APIC frequently offers, throughout the country, educational training in basic infection control practices. This program includes topics of surveillance methodology, basic microbiology, immunology, infectious process, infection-control precautions, and outbreak investigation. This will provide the staff member a good foundation for establishing an infection control program and setting up surveillance protocols. Advance training and certification programs are also available from APIC for the ICP. Membership in APIC affords the opportunity for networking with other ICPs in an exchange of ideas and problem-solving. Also, subscriptions to periodicals or Internet links give access to information on infection control practices. This information is essential to maintain updated and current information on changes and trends in the field of infection control (10). B. Staff Education The ICP should provide ongoing infection control education for all levels of LTCF staff, both for the direct caregivers (nurses, nursing assistants, therapist, etc.) and ancillary staff (maintenance, dietary, housekeeping, etc.) Education should include information on: • How infections are transmitted • What makes residents susceptible to infections • Standard and transmission-based precautions

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• Antibiotic-resistant microorganisms • The importance of basic hand washing • How the infection control program functions The ICP must be aware of staff concerns related to caring for residents with infections. For example, a resident with a Foley catheter is newly diagnosed with urinary tract infection with MRSA. The caregivers are concerned that they have been caring for this resident and the resident has not been on contact precautions. Additional training in standard precautions, non-resistant staphylococcal versus MRSA infections, and the role of susceptibility in acquiring infection may be required to alleviate staff concerns. C. Tips on Nursing Care for Infection Prevention 1. Proper Foley catheter insertion using aseptic technique and proper/frequent Foley catheter care will assist in decreasing the number of urinary tract infections (12). Adequate fluid intake should be maintained, when not medically contraindicated, to help prevent urinary tract infections. 2. Preventive measures for decreasing the development of pressure ulcers and related infection complication include the following: • Schedule toileting for incontinent residents. • Turn schedule/pressure relieving mattresses for residents at risk while in bed. • Elevate heels off the mattress with pillows. • Position devices in bed, recliners, wheelchairs. • Maintain good nutritional and fluid intake. • Use lift sheets and two employees when changing resident’s position. • Adhere to a position change schedule when a resident sits in a chair, recliner, or wheelchair. 3. When a resident is on antibiotic therapy, offering yogurt or buttermilk may help prevent yeast infections and assist in maintaining normal bacterial flora. 4. A policy that residents do not have contact with staff members who are diagnosed with an infection should be enforced. Infected staff members should also use appropriate protective equipment, (e.g., mask when infected with a respiratory infection) to safeguard the residents. 5. Employees should use gait belt when transferring, repositioning in a wheelchair, and ambulating residents to decrease the chance of skin tears or lacerations that would put the resident at risk for infection. 6. An active immunization program for current residents, new admissions, and employees should be implemented (13). Although these types of programs may be expensive, it will be more costly to treat multiple active infections.

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a.

Residents • Annual influenza vaccination should be administered after the last week in October to assure continued antibody levels throughout the “flu” season. • D/T (diphtheria/tetanus toxoid) booster when source of skin tears, lacerations, or puncture wounds is unknown and resident has not had a booster in more than 10 years. • D/T booster every 10 years when no major injuries have occurred. • D/T booster in the case of a major injury if no booster administered in more than 5 years. • Pneumococcal vaccine for all new residents without prior immunization. b. Staff • Measles, mumps, and rubella vaccine for all employees born after December 31, 1956 if they are unable to provide verification of prior immunization • Influenza vaccine annually • Hepatitis B vaccination 7. Tuberculin skin testing with purified protein derivative (PPD) is recommended for all new residential admissions using a two-step Mantoux method. New staff, staff exposed to active tuberculosis, and staff as part of their annual employment examination should receive a PPD skin test. VI. CONCLUSION The staff will need continuing education on changes that occur with aging and how symptoms and signs of infection may manifest differently in the geriatric population. The staff should understand what is “normal” for each resident under their care. The nurse must give careful attention to the culture and sensitivity reports to assist the physician in decreasing the inappropriate use of antibiotics. The staff needs to continue to improve resident assessment skills to identify the presence of infection and to work on effective communication skills to relay this information to the physician and other personnel, as appropriate. Knowledge of and adherence to infection control procedures and practices are essential in preventing infections and outbreaks. REFERENCES 1.

U.S. Department of Health and Human Services, Health Care Financing Administration. Medicare and Medicaid requirements for long term care facilities. Federal Register September 26, 1991; 56:48826–48879.

114 2. 3.

4. 5. 6.

7.

8. 9. 10. 11.

12.

13.

Barton and Register Smith PW, Rusnak P. APIC guideline for infection prevention and control in the long-term care facility. Am J Infect Control 1991; 19(4):198–215. McGeer A, Campbell B, Emori TG, Hierholzer WJ, Jackson MM, Nicolle LE, Peppler C, Rivera A, Schollenberger DG, Simor E, Smith PW, Wang EE-L. Definitions of infection for surveillance in long-term care facilities. Am J Infect Control 1991; 19(1):1–7. Christensen PJ, Kenney JW. Nursing Process Application of Conceptual Models, 3rd ed. St. Louis, The C. V. Mosby Company, 1990. Shua-Haim JR, Ross S. Pneumonia in the elderly. Clinical Geriatrics (on-line). Available at: http://www.mmhc.com/cg/articles/CG0001/shua.html. Fune L, Shua-Haim JR, Ross JS, Frank E. Infectious diseases in the elderly. Clinical Geriatrics (on-line). Available at http://www.mmhc.com/cg/article/CG9803/ShuaHaim.html. Rajagopalan S, Moran D. Infectious disease emergencies in older adults. Clinical Geriatrics (on-line). Available at: http://www.mmhc.com/cg/article/CG101/ raja.html. Garner J. Guideline for isolation precautions in hospital. Infect Control Hosp Epidemiol 1996; 17(1):53–80. Barrs AW, Fahey P. Infection control across the board. Nurs Homes Long Term Care Management 2000; 49(11):38–43. Pritchard V. Joint Commission standards for long-term care infection control: Putting together the process elements. Am J Infect Control 1999; 27(1):27–34. Smith PW, Rusnak PG. Infection prevention and control in the long-term-care facility. Am J Infect Control 1997; 25(6):488–512. http//www.nih.gov/ninr/vol3/Infection.html. Fune L, Shua-Haim JR, Ross JS, Frank E. Infectious disease among residents of nursing homes. Ann Long-Term Care 1999; 7(11):410–417. Available at: http://www. mmhc.com/nhm/articles/NHM9911/shuahaim.html. Drinka PJ, Gravenstein S. Management of influenza in the nursing home. Ann LongTerm Care 2000; 8(9):23–30.

9 Establishing an Infection Control Program Janet Nau Franck Consulting Professionals, Inc., St. Louis, Missouri

Elizabeth Owens Schwab BJC Health System, St. Louis, Missouri

David W. Bentley Saint Louis University School of Medicine, and St. Louis VA Medical Center, St. Louis, Missouri

I. INTRODUCTION In one’s lifetime, the potential for entering a long-term care facility (LTCF) continues to increase along with its risk. It is estimated that more than 40% of persons aged 65 and older will require an LTCF, such as a skilled nursing facility, sometime during their lifetime. Because of their multiple underlying risk factors, the possibility of infection increases, but chronic illness, dementia, overuse of antibiotics, and lack of diagnostic resources all contribute to the delay or inability to promptly recognize and treat infection (1). It is no surprise, therefore, that infection control practices in LTCFs are being recognized as a critical component in the prevention and control of infections. This chapter provides practical guidelines for establishing and maintaining an effective infection control program in the LTCF, including useful practices and resources for the beginning infection control professional (ICP). A resource that provided much of the focus for this chapter was previously published (2) (see also Chapters 8 and 10.)

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II. THE CASE FOR ESTABLISHING AND MAINTAINING AN EFFECTIVE INFECTION CONTROL PROGRAM A. Increased Infection Risk in the Elderly The increasing numbers of frail older persons requires that more care be provided in LTCFs such as nursing homes, especially skilled nursing facilities. Many of these residents are immunocompromised because of comorbidities, medications, and functional disabilities. These residents require comprehensive infection control programs targeted toward the high risks of infection imposed by the special conditions of the LTCF and the residents’ own susceptibilities. High employee turnover rates and multiple facility priorities continually thwart effective infection control programs. Such challenges undermine even the best, most organized infection control effort. The nature of the LTCF resident’s immune suppressed state, combined with the challenges of day-to-day facility operations require constant vigilance toward infection control and prevention. B. Regulatory Requirements 1. Mandated Federal, State, and Local Requirements Mandated requirements from federal regulatory and advisory agencies, such as the Health Care Financing Administration (HCFA) (3) and the Occupational Safety and Health Administration (OSHA) (4), require that LTCFs comply with their written directives as outlined in their survey manuals. These requirements reflect a number of infection control issues. The OSHA Bloodborne Pathogen Standard (4) focuses primarily on minimizing exposure of bloodborne pathogens to health care workers, for example human immunodeficiency virus (HIV) and hepatitis B. Additionally, regulatory requirements by HCFA and the Omnibus Budget Reconciliation Act (OBRA) (5) address federal regulations that mandate that LTCFs establish prevention and control of infections associated with admission to, or employment in, such a facility. It is most helpful to take a core set of requirements from these and other agencies and adapt them to the LTCF’s needs. The infection control program also needs to be compliant with local and state requirements that relate to the prevention and control of infections in LTCFs (6). This information can be obtained from an LTCF administrator or the state Department of Health. Many of these agency requirements are similar. For example, recommendations overlap in addressing policies regarding (1) admissions, (2) tuberculin testing of residents, (3) employee health, (4) immunizations, (5) HIV-infected residents, and (6) infection control (6). It is essential to focus on the adaptation of standards applicable to your facility’s needs to obtain licensure and comply with regulatory requirements.

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2. Voluntary Organization Requirements An example of voluntary organization requirements is the Joint Commission on Accreditation of Healthcare Organization (JCAHO), which publishes long-term care standards (7). These standards address a number of infection control issues, and compliance with these standards is necessary to attain JCAHO accreditation. An additional resource is published by the American Health Care Association (8).

III. ESSENTIAL ELEMENTS OF AN EFFECTIVE INFECTION CONTROL PROGRAM A. Program Elements 1. Oversight Committee A committee with oversight responsibilities for an infection control program should be organized to provide the necessary authority and decision-making functions for an effective program. Although the committee may meet only as needed or be combined with the work of other committees, such as quality improvement, pharmacy review, or occupational health and safety, its purpose should be to oversee the process of reducing the risks of facility-acquired infections in residents and healthcare workers (7). The committee also serves to review and analyze surveillance data and collectively approve recommendations for ongoing prevention and control measures. It acts as the enforcing body within the organization for continuous application of good infection control practice throughout the facility and takes action, as necessary, to implement emergency control measures during an outbreak. The oversight committee should have appropriate authority from the administrative and medical leadership. The committee, therefore, should include the medical director, the director of nursing, the ICP, and a representative from each of the following areas: nursing staff, administration, and other clinical departments such as rehabilitation, dietary, pharmacy, housekeeping/maintenance, and others. If the ICP and quality improvement professional are not one and the same, the group should also include the individual responsible for coordinating the facility’s performance improvement process (7). The essential elements of an effective infection control program in LTCFs have been identified (8–10) and include the oversight committee and other elements shown in Table 1 and described below. 2. Infection Control Professional One author describes the ICP as the “eyes, ears and feet of the infection control program” (11). The ICP assesses, gathers information (surveillance), and moves throughout the facility not only to gather information but to implement or enhance

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Table 1 Essential Elements of an Effective Infection Control Program in the Long-Term Care Facility Oversight committee Infection control professional Infection control program elements Infection surveillance Infection control interventions Outbreak investigation and control Education for employees, residents, and visitors Policy and procedure development Employee health program Resident health programs Antibiotic resistance management Antibiotic utilization and review Effective interdepartmental partnerships Disease reporting to public health departments

existing prevention and control measures. The designated person responsible for coordinating the infection control program is usually a staff nurse. It is ideal for this person to be a registered nurse and work closely with the director of nursing. Appropriate delegated authority, clinical background, infection control training, and nursing’s multiple roles in the LTCF are important variables in the ultimate success of the ICP role. Each of these factors plays a vital role in how the ICP will function on a day-to-day basis and consequently, may largely contribute to, or detract from, the efficacy of the overall infection control program. The LTCF must wholly support the ICP and the efforts for surveillance and infection prevention. Without this support, access to important information may be blocked, partnerships with other departmental managers may fail, and most importantly, the facility may not receive vital data on facility-acquired infection, which will be needed to improve resident care. It is important that the ICP have a clinical background—ideally in nursing, preferably in caring for the elderly. Knowledge of microbiology and a general understanding of antibiotic use are also helpful. Infection control training and exposure to available resources are the foundations of the ICP’s successful job role. Basic knowledge of infection control standards, methods of surveillance, and requirements for an effective program can be obtained via textbook, journal, and Internet access. To access these resources, the professional must be allocated the time and financial resources to purchase or borrow from a medical library such items and digest the information they offer. Several websites for infection control information have been included at the end of this chapter. To use these websites, the ICP must have access to a personal computer with Internet connection and, again, the time to review the information. Several courses given

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by national or regional groups are also available. The Association for Professionals in Infection Control and Epidemiology (APIC) offers a training course for hospital and LTCF ICPs (202-296-2742). The Missouri Chapters of APIC offer the “Essentials of Infection Control Annual Conference” yearly in mid-Missouri (573-893-3700), and the Nebraska Infection Control Network offers a basic training course specifically for LTCF ICPs (402-552-2360). 3. Infection Surveillance a. Endemic Rates. Routine infection surveillance is the cornerstone of the infection control program. The facility should use surveillance data to drive infection control interventions and decision-making for infection prevention. If surveillance data are given to clinicians and staff on a regular basis, the information can serve to initiate improvement in resident care. It can also be used to display successes in infection rate reduction as a means to reach administrators or others who allocate resources for infection control and prevention. Essential elements of surveillance are described in Table 2. The surveillance program should include a consistent and systematic data collection process with written definitions. The population(s) of interest, for example, residents with Foley catheters or pressure ulcers, should be defined. Data should then be collected and consolidated for routine but meaningful reporting and evaluation. Analysis and interpretation should be conducted regularly. Surveillance data should be used

Table 2 Essential Elements of Surveillance for Infection Control Element

Description

Comment

1. Data collection

Systematic data collection

2. Documented surveillance process 3. Review and analysis

Documented surveillance

Defined numerator/denominator Written process with written definitions Include type of infection and date of onset

4. Rate calculation and reporting 5. Data used for IC intervention planning

Frequent data review/swift control measures as appropriate Periodically calculate and report rates (monthly, quarterly) Use surveillance data to drive IC efforts

Abbreviation: IC, Infection control. Adapted from Ref. 9.

Use standardized rate calculation/1000 resident days Short-term planning and long-term priority setting

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in the short term to plan immediate infection control measures or educational programs, detect epidemics, or identify individual resident problems for intervention or treatment. For the long term, surveillance data can be used to determine ongoing educational needs, resource allocation for upcoming years, and objectives for infection control planning in subsequent years. Definitions for LTCF-acquired infection. Although standard definitions for nosocomial infection in acute care have long been available (12), no similar set of definitions has been validated for LTCFs. A panel of experts published a set of LTCF-acquired infection definitions by body site established by consensus conference methods that have been widely adopted by LTCF infection control programs (13) (see Appendixes). The definitions should be written and kept in a central location such as the infection control manual or on personal computer disk so that the ICP or other members of the organization can access them at any time. This becomes particularly important in the LTCF where turnover rates can be high and new individuals will frequently need to be trained on the surveillance process. Data collection reporting and rate calculations. Ideally, the ICP will use standardized data collection methods and tools to obtain surveillance information. This approach, along with the use of specific definitions, helps assure consistency of data collection and analysis for comparison over time. Sources for obtaining infection information are described in Table 3. The ICP’s presence in the resident care areas shows staff that infection control is important and that administration supports infection control and values adherence to good infection control practice. Infection rates are used to provide a common basis for entering surveillance data. Rates require a numerator, or number of nosocomial infections in a given period, for example, the number of urinary tract infections in July, and a denominator, which in LTCFs is the population at risk or total number of resident-days in July. For example, if the LTCF had an average daily census of 140 for July and 14 new infections were detected, the rate would be 14/140  31  1000  3.2 infections per 1000 resident-days. For further details on data collection, reporting,

Table 3 Sources for Infection Information Patient-based Resident assessment, hall rounds, staff communication, medical record, X-ray reports, Kardex review, temperature logs, medication/pharmacy records/treatment logs Laboratory-based Microbiology reports, antimicrobial susceptibility reports Other departments or agencies Admissions/social work/rehabilitation, physician offices or outpatient clinics, home care/home infusion agencies, acute care facilities, state and local health departments

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and rate calculations and their use in infection control programs in LTCFs, other reference sources are available (11). b. Epidemic Rates. Surveillance data provide the basis upon which the ICP may identify an epidemic or outbreak of a particular infection type. Day-to-day collection of surveillance data allows the opportunity for early detection of such epidemics. Epidemic rates are infection rates of a particular type or organism that are higher than expected. For some organisms, one or two cases may be considered an epidemic, for example, hepatitis A or group A Streptococcus. For others, several isolates with similar antibiotic susceptibility patterns or other common features, such as common body site or common resident location, must be present to initiate outbreak or cluster investigation. Examples of the latter include methicillin/oxacillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). 4. Outbreak Investigation and Control As discussed above, an outbreak or epidemic is an occurrence of similar infections at a rate that exceeds the rate normally expected in a given location and period. Although most facility-acquired infections in LTCF are endemic, a portion do occur from outbreaks. Aggressive detection and control are important because of potential morbidity and mortality to residents and staff, subsequent cost of investigation and treatment, and public relations difficulties often related to outbreak occurrence. An outbreak can be one case of a disease of unusual virulence or public health importance, as noted above. For less virulent organisms, an outbreak can be defined as three or more cases related by time, place, and person within the same population (see also Chapter 10). Knowing the usual endemic baseline rates, the ICP can also suspect an outbreak by noticing infection rates equal to 2 1/2 times above the usual rates. Some experts in infection control in LTCFs have suggested identifying outbreaks by threshold testing, which uses a simplified table of binomial distributions to calculate probabilities of infection frequency at selected endemic levels (mean number of infections per month) and compares these probabilities to observed infection frequency. This method is straightforward and does not require knowledge of statistics, special computer software, denominators, or calculation of rates (14,15). Table 4 lists the appropriate steps to outbreak investigation in a LTCF. 5. Education for Employees, Residents, and Visitors Infection control inservice education should be provided by the ICP and department supervisors to all employees on a timely basis, particularly during their orientation. Documentation of training should reflect the dates, times, attendees, and evaluations. Topics should reflect the goals identified in the infection control pro-

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Table 4 Steps to Outbreak Investigation in a Long-Term Care Facility Request help, notify state and local health departments Control the known Determine case definition Compile line list of initial cases; seek additional cases that fit definition Initiate additional/extend original control measures to more areas based on case finding Inform and educate staff, residents, families Check for daily new cases until occurrences cease Present follow-up report to administration and health department: compile all documentation (epidemiologic curve, line list, description of control measures)

gram plan and concerns identified from surveillance data. For example, before the influenza season, presentations should identify symptom recognition, transmission of the infection, vaccination and chemoprophylaxis policies, the importance of hand washing and other hygienic practices, appropriate waste disposal, bagging at the point of contact and universal precautions. Coordinated effective educational programs will result in improved infection control activities (8,16,17). Infection control-related education of residents and visitors can help reduce the risk of transmission of pathogens by resident-to-resident or resident-to-visitor contact and decrease the level of stress for both parties. For example, the APICOrange County Patient and Family Education Task Force has developed a series of 20 education pamphlets that can be accessed by computer disk and customized for individual LTCF needs. These educational pamphlets can be adapted to enhance resident and family understanding of how to minimize the transmission of infection. These could be translated to other languages when such barriers are a concern. For additional information, see the Appendix at the end of this chapter. 6. Policy and Procedure Development An important aspect of the infection control program is the development, review, and updating of policies and procedures (P&Ps). This requires the ICP to be available to make rounds, provide educational input, and monitor compliance of P&Ps to ensure adherence. Many areas should be considered when establishing infection prevention and control. Resources are available to assist in the development and writing of these P&Ps (9,18) (see also the Appendix at the end of this chapter for additional sources). Table 5 lists a good sampling of P&P topics to include. The P&Ps need to be clearly written, updated, and referenced on a timely basis. Staff should be oriented to them as they pertain to the performance of their job. Departmental supervisors should be consulted in the drafting of their P&Ps and present them to the infection control committee for final approval. These P&Ps require regular review and approval for example, every 2 years. An inter-

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disciplinary approach is essential when developing these P&Ps, including administration, nursing, medical, and support services/departments. The infection control committee minutes should document this approach for accreditors and serve to track their review and expansion. Policies and procedures are critical to the success of the program. They serve as the basis for procedural inservices, staff performance, and they demonstrate competency and program evaluation. As a resource, they should be closely aligned with the mission and vision of the organization to promote a team focus (19). 7. Employee Health Programs The health of the employee is important to the delivery of safe care for all residents. This includes the requirements that employees should be hired without communicable diseases (3) and are protected from occupational exposure to bloodborne pathogens (4). Guidelines for infection in hospital personnel are available (20) and are generally adaptable to the LTCF (9). Other important issues that are not mandated but on which employees should be instructed are the sick and accident policy and post-exposure follow-up or preventative programs for certain infections, such as HIV, hepatitis B virus, and scabies or lice (9). Tuberculosis screening and education is a key element in the employee health program. Major components for instruction by the ICP include the two-step tuberculin skin test, interpretation of test results, follow-up of positive skin tests, and staff awareness of their symptoms and signs that may represent Table 5 Sample List of Policies and Procedures for Infection Control in Long-Term Care Facilities Role of administration Hand washing Universal precautions/isolation Housekeeping, e.g., cleaning processes, waste disposal, and environmental surveillance Laundry, e.g., handling of soiled linen Dietary, e.g., food preparation and cleaning Rehabilitation services, e.g., physical therapy, occupational therapy Respiratory therapy, e.g., humidifier cleaning Employee health, e.g., tuberculosis screening and vaccinations and leave of absence Admission to the long-term care facility Transfer to an acute care facility Vaccination history, e.g., influenza, pneumococcal, and tetanus Management of residents with infections Infection surveillance and data collection Outbreak identification, investigation, and control Review antibiotic prescribing

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active tuberculosis pulmonary disease (21). Employee vaccination programs should include influenza, hepatitis B vaccine, varicella, and hepatitis A virus, in certain circumstances (9). (See other chapters in this book relevant to these topics for further details). Organizations such as APIC and health departments can provide literature, media material, and “tool kits,” that is, work sheets and educational aids, to further promote the understanding of and compliance with these challenging employee health issues (see also the Appendix at the end of this chapter for these sources). 8. Resident Health Program Residents need to be screened on admission to the LTCF to assess their risk for transmitting an infection, as well as their need for preventive interventions to reduce their risk for contracting infection (22). A major component of a resident health program is immunizations for influenza, pneumococcal disease, and tetanus (9) (see Chapter 20). In addition, all residents on admission should undergo tuberculin skin testing and a follow-up chest X-ray if the skin test is positive or the patient is symptomatic (21) (see Chapter 15). Other interventions should be targeted toward the prevention of urinary tract infections, skin and soft tissue infections, and aspiration pneumonia (9) (see chapters on these topics in this book). 9. Antibiotic Resistance Antibiotic resistance is a major concern in LTCFs. Residents most likely to develop infections caused by resistant organisms are those with wounds such as pressure ulcers, underlying chronic diseases, poor functional status, invasive devices such as urinary catheters, and prior antibiotic therapy. Because these resistant organisms may enter the facility through colonized or infected hospital patients and become endemic, strategies must be established by LTCFs to control their spread. Person-to-person transmission via the hands of healthcare workers appears to be the most important means of spread (23). Strategies to control transmission of antibiotic-resistant pathogens in LTCFs is limited, and strategies used in hospitals often are inapplicable. The Society for Healthcare Epidemiology of America (SHEA) position paper (23) provides a good discussion of this problem. In addition, Section III of this book provides several chapters on antimicrobial resistance in LTCFs. 10. Antibiotic Utilization An important contributing factor to the growing problem of antibiotic resistance is the overusage and inappropriate prescribing of antibiotics in LTCFs. To improve antimicrobial use, a second SHEA position paper (24) recommended that LTCFs develop and implement several control measures. Infection control pro-

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grams should include antibiotic utilization review of the antibiotics that are being prescribed in the LTCF to help limit the potential for the spread of resistant organisms. Others have recommended that the key data to collect include: (1) incidence (number of antibiotic courses started per 1,000 resident-care days) and (2) antibiotic utilization ratio (ratio of number of antibiotic-days to number of resident-care days). Because the costs of antibiotics are often easily available from administration and pharmacy and appear to reflect overall antibiotic use, data on antibiotic costs per resident-care-day can serve as an alternative to the intensive utilization review items noted (25) (see Chapter 11). 11. Effective Partnerships a. Alliance with Administration, Medical Director, and Director of Nursing. Before establishing a new (or enhancing an existing) infection control program, the facility administrator must fully appreciate the importance of infection control. Not only must the administrator understand the increased infection risk for the resident, but also the increasing regulatory requirements for infection control as a condition of participation in Medicare. To educate the administrator on the value of an excellent infection control program will require the full support and promotion by those who first see it as valuable: the medical director (MD) and the director of nursing (DON). Depending on the LTCF, the education process for the administrator by these healthcare professionals may require first demonstrating the need for an ICP. Collaboration between the MD and DON or ICP is critical in making the process a success. After the MD/DON team has educated the administrator on these components, the administrator should be presented with a proposal for resources needed. Each program should include several essential elements for success, for example surveillance program, isolation policies, employee education, and others as noted in Table 1. The overall program will require several resources to ensure its success. The key resources include: an ICP with knowledge of or supporting resources for fundamentals of infection control, Internet access and, if possible, appropriate computer software and hardware to manage a surveillance database, adequate workspace, and sufficient medical and administrative support to influence others in the facility, even without having direct authority over them. b. Alliance with Department Manager/Supervisors/Nursing. In all areas, the ICP must communicate closely with staff to ensure that they have the knowledge, expertise, and supplies necessary to comply with standard precautions, isolation practices, aseptic technique, and other problem-specific issues. An effective strategy to identify unsafe practices is to perform walking rounds, document issues of noncompliance, and distribute the findings to the individual department manager/supervisors. Noting practices such as breaks in aseptic technique is essential in recognizing opportunities for improvement, such as wearing gloves inappro-

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priately or not bagging and knotting bags of soiled items at the point of use. Is there an availability of personal protective equipment (PPE) in soiled utility rooms when cleaning reusable medical devices? Does the trash that is placed in biohazardous waste containers meet the definition of being blood “soaked or caked,” as mandated by OSHA? Is the facility paying for additional poundage of regular trash to be transported by special waste handlers? Are food products labeled and dated, and are refrigerators being cleaned after spillage on a routine basis? If not, education can act as a critical means of modifying behavior. c. Quality Improvement. Long-term care facilities have continued to emphasize quality improvement (QI) processes. There are a number of similarities between QI and infection control programs. Both use methods to collect data, then search for adverse outcomes or risk-reducing strategies. Both programs demonstrate the value of education to change behavior and both perform follow-up evaluations to determine if outcomes have improved. Infection control continues to be recognized as a performance improvement process due to the analytic process of collecting surveillance data, identifying areas of concern, and recognizing opportunities for improvement. For this reason, many LTCFs have used the QI committee meetings as a successful means of discussing and documenting infection control program activity (26). d. Environmental Hygiene. The LTCF must be monitored for cleanliness and proper maintenance because residents may often soil with body secretions and discharges with which the physical environment they come in contact. This can then serve as a reservoir for spreading infections to other residents and staff. These housekeeping policies must delineate the process and persons responsible for cleaning and disinfecting the environment. Cleaning schedules need to be closely followed, ensuring that cleaning products are facility-approved and dilutions are appropriate and standardized. Hand-washing facilities should be conveniently located and accessible to all staff. Insects and rodents must be eliminated and prevented from gaining access to the LTCF. Maintenance also plays a vital role in assessing and maintaining safe plumbing and ventilation systems of the facility. For example, their policies should indicate that air filters are changed routinely to avoid contaminating the environment or themselves. For laundry services, the ICP needs to monitor that bagging of linens at the site of use, that clean linens are covered, and that carts are cleaned between uses. In the laundry, separate areas must be designated for clean and soiled items. Physical therapy equipment, especially hydrotherapy equipment, should be disinfected regularly and anytime there is visible soiling with bloody fluids. In food service, because of the risk of foodborne illnesses, it is important that the food preparation and services environment be clean and strict attention given to food handlers. The infection control program, with support from risk management, maintenance, and housekeeping, should establish and monitor policies and procedures for disposing

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of infectious or other waste materials, as defined and regulated by federal, state, and local regulations, including OSHA regulations (4), to minimize cost and occupational exposure risk to healthcare personnel (27). e. Admissions/Social Worker. Admissions and Social Work have key roles in facilitating the transfer of patients from the hospital to the LTCF, with special emphasis on infection control issues. The admission process should include clear and accurate information regarding the infection control risks of the patients before their transfer to the LTCF. For example, the transferring hospital facility should notify the LTCF regarding a patient harboring an antibiotic-resistant organism, the results of tuberculin skin testing, or other conditions for which additional precautions should be considered. All employees need to be reminded of the importance of confidentiality, whether the infection is HIV or MRSA. It is helpful for hospitals and LTCFs to formalize joint transfer agreements in advance to expedite processes and clarify policies. Of course, transfer of residents to hospitals require that equally clear and accurate infection control-related information be transmitted to the hospital prior to transfer. IV. BARRIERS TO ESTABLISHING AN EFFECTIVE PROGRAM Despite the LTCFs best efforts to create an effective infection control program, most facilities face formidable barriers in maintaining the program. The complicated work of resident care is strenuous and fast-paced, often leading to high turnover rates even among LTCF administrators, DONs, and ICPs. This necessitates frequent retraining and resecuring of infection control resources. Direct resident care staff also turnover quickly, which presents education challenges on a daily basis. Because many LTCFs are small (fewer than 200 beds), the ICP is often assigned multiple roles. Although not unimportant, these other responsibilities may serve to distract the ICP from constant focus on infection surveillance and control measures. Other barriers include lack of infection prevention and control training, lack of necessary resources to implement an effective program and perhaps, most importantly, lack of strong administrative or medical support in the form of true delegated authority. As described above, basic infection control training is the foundation of a successful ICP role and is often both inexpensive and easy to access. The ICP must, however, have the time and means to access such educational resources. Other necessary resources that may be lacking include: desk/office space, Internet access and, possibly, computer hardware and software, secretarial or data entry support, time away from resident care for staff to attend infection control inservice education, access to local/regional resources, and time to attend local and regional APIC meetings.

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V. LOCAL, REGIONAL, AND NATIONAL RESOURCES A. Local APIC Chapter Becoming a member of a local chapter enables the ICP to take advantage of numerous products, services, and educational opportunities that are timely and stateof-the-art. Whether it is the cutting-edge training courses the ICP needs, information regarding practice standards, networking opportunities, information technology resources, or practice guidelines, becoming a member of a national infection control association such as APIC can initiate the ICP’s training and support needs (see the Appendix at the end of this chapter for additional information). B. County and State Departments of Health Another important element of the infection control program is to submit reportable diseases to the public health department. The ICP needs to know which diseases must be reported by law and the process most efficient to ensure complete and accurate reporting. Depending on the surveillance system established, the ICP needs to determine who will report diseases when the ICP is on vacation or not available. The reportable diseases are critical data to the public health departments, which rely on this information to provide educational and laboratory services for program planning and development. The State Communicable Diseases section also can serve as valuable consultants and provide useful information on current clusters or outbreaks of infection control problems in other LTCFs in the same locale. C. APIC/SHEA Several professional associations provide significant resources to ICPs and LTCF staff. The Association for Professionals in Infection Control and Epidemiology provides a quarterly Long Term Care Newsletter, journal articles in the American Journal of Infection Control, and a Long Term Care Section that meets at annual conferences and provides resources accessible from their web site. The Society of Health Care Epidemiology of America has a Long-Term Care Committee and publishes in the journal, Infection Control and Hospital Epidemiology, helpful guidelines on pertinent infection control-related topics that are frequently seen in LTCFs (see the Appendix at the end of this chapter for websites).

VI. PROGRAM EVALUATION AND IMPROVEMENT Developing an annual plan and an evaluation and improvement program can start the ICP’s efforts to maintain administrative support and confidence in the infec-

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tion control program. Because each facility is unique, every effort should be made to address concerns that are specific to one’s own LTCF. Risk factors, resident population, and the nature of the LTCF will determine the criteria used for program planning and evaluation (28). As long as the outcome invites an opportunity for improvement, the quality of care will be positively enhanced. An excellent tool to use when evaluating your program is the APIC toolkit, “Assessing and Developing an Infection Control Program.” Although this was written with the acute care setting in mind there is little difference between the program processes and methods to evaluate the effectiveness of the LTCF program (see the Appendix for source information).

APPENDIX Supplementary Reading List APIC Text of Infection Control and Epidemiology, 2000. APIC National Office, 1275 K Street NW, Suite 1000, Washington, DC 20005-4006. Can be ordered by phone: (202) 789-1890. Contains all current APIC Guidelines, State of the Art Reports, Position Papers, Commentaries, CDC and OSHA Guidelines. Arias K (ed). Assessing and Developing an Infection Control Program in the Acute Care Setting (and adaptable to LTCF). Infection Control Tool Kit Series, 2000; APIC National Office, 1275 K Street NW, Suite 1000, Washington, DC 20005-4006. Can be ordered by phone: (202) 789-1890. Contains useful guidelines, sample forms, documents and references. Benenson AS (ed). Control of Communicable Diseases in Man, 15th ed. 1990. American Public Health Association, 1015 Fifteenth Street NW, Washington, DC 20005. Lists infectious diseases with signs, symptoms, epidemiology, contagious periods and treatment. Heaton WH, Thayer NL. Infection Control Program: Policy and Procedure Manual (for LTCFs). National Health Publishing, 428 E. Preston St., Baltimore, MD 21202, tel. 301528-4000. Useful resource for developing an IC program. Patient and Family Education (Pamphlets) disk, APIC Orange County: APIC National Office, 1275 K Street NW, Suite 1000, Washington, DC20005-4006. Can be ordered by phone. (202) 789-1890. Contains educational infection control pamphlets that can be customized. Selected Internet Websites Association for Professionals in Infection Control and Epidemiology (APIC) http://www.apic.org/ Center for Disease Control and Prevention (CDC) http://www.cdc.gov/ Occupational Health and Safety Administration (OSHA) http://www.osha.gov/ Society for Healthcare Epidemiology of America (SHEA) http://shea-online.org World-Wide Web Virtual Library: Epidemiology http://www.epibiostat.ucsf.edu/ epidem/epidem.html/

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Bentley DW, Bradley S, High K, Schoenbaum S, Taler G, Yoshikawa TT. Practice guideline for evaluation of fever and infection in long-term care facilities. Clin Infect Dis 2000; 31:640–653. Smith PW. Infection control program organization. In: Smith PW (ed). Infection Control in Long-Term Care Facilities, 2nd ed. Albany, NY, Delmar Publishers, 1994: 105–114. U.S. Department of Health and Human Services, Health Care Financing Administration. Medicare and Medicaid requirements for long term care facilities. Federal Register September 26, 1991; 56:48826–48879. Department of Labor, Occupational Safety and Health Administration. Occupational exposure to blood-borne pathogens: Final rule. Federal Register December 6, 1991; 56(235):64004–64182. Omnibus Budget Reconciliation Act of 1987. Pub L No. 100–203, December 22, 1987, subtitle C, part 1, 4201:160–170. Crossley K, Nelson L, Irvine P. State regulations governing infection control issues in long-term care. J Am Geriatr Soc 1992; 40:251–254. The Joint Commission on Accreditation of Healthcare Organizations. Comprehensive Accreditation Manuals for Long Term Care. Chicago, IL, Joint Commission on Accreditation of Healthcare Organizations, 1998. American Healthcare Association. Infection Prevention and Control for Long-Term Care Facilities: Handbook and Instructor’s Guide. Washington, DC, AHCA, 1995. Smith PW, Rusnak PG. Infection prevention and control in the long-term care facility. Am J Infect Control 1997; 25(6):488–512. Rusnak PG. Long-term care. In: Pfeiffer J (ed). APIC Text of Infection Control and Epidemiology. Washington, DC, APIC, 2000:17-1–17–31. Rusnak PG, Horning LA. Surveillance in the long-term care facility. In: Smith PP (ed). Infection in Long-Term Care Facilities, 2nd ed. Albany, NY, Delmar Publishers 1994, 10:117–130. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Control 1988; 16:128–140. McGeer A, Campbell B, Emori T, Hierholzer WJ, Jackson MM, Nicolle LE, Peppler C, Rivera A, Schollenberger DG, Simor AE, Smith PW, Wang EE-L. Definitions of infection for surveillance in long term care facilities. Am J Infect Control 1991; 19:1–7. Mylotte JM. Analysis of infection control surveillance data in a long-term care facility: Use of threshold testing. Infect Control Hosp Epidemiol 1996; 17:101–109. Smith PW. Epidemic investigation. In: Smith PW (ed). Infection Control in LongTerm Care Facilities, 2nd ed. Albany, NY, Delmar Publishers, 1994:131–146. Smith PW, Daly PB, Rusnak PG, Roccaforte JS. Design and dissemination of a multiregional long-term care infection control training program. Am J Infect Control 1992; 20:275–277. Daly PB, Smith PW, Rusnak PG, Jones MB, Guiliano D. Impact on knowledge and practice of a multi-regional long-term care facility infection control training program. Am J Infect Control 1992; 20(5):225–233.

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Rusnak PG, Boehle MC. Regulation, policies and procedures. In: Smith PW (ed). Infection Control in Long-Term Care Facilities, 2nd ed. Albany, NY, Delmar Publishers, 1994:161–168. Pritchard V. Joint commission standards for long-term care infection control: Putting together the process elements. Am J Infect Control 1999; 27:27–34. Diekema DJ, Doebbeling BN. Employee health and infection control. Infect Control Hosp Epidemiol 1995; 16:292–301. Centers for Disease Control. Prevention and control of tuberculosis in facilities providing long-term care to the elderly. MMWR 1990; 39(No. RR-10):7–20. Yoshikawa TT, Norman DC. Infection control in long-term care. Clin Geriatr Med 1995; 11:467–480. Strausbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term-care facilities. Infect Control Hosp Epidemiol 1996; 17:129–140. Nicolle LE, Bentley DW, Garibaldi R, Neuhaus EG, Smith PW, and the SHEA LongTerm-Care Committee. Antimicrobial use in long-term-care facilities. Infect Control Hosp Epidemiol 2000; 21:537–545. Mylotte JM. Antimicrobial prescribing in long-term care facilities: Prospective evaluation of potential antimicrobial use and cost indicators. Am J Infect Control 1999; 27:10–19. Smith PW. Infection control program organization. In: Smith PW (ed). Infection Control in Long-Term Care Facilities, 2nd ed. Albany, NY, Delmar Publishers, 1994: 105–114. Haberstich NJ. Infection control measures: The environmental reservoir. In: Smith PW (ed). Infection Control in Long-Term Care Facilities, 2nd ed. Albany, NY, Delmar Publishers, 1994:211–216. Smith PW. Infection surveillance in long-term care facilities. Infect Control Hosp Epidemiol 1991; 12:55–58.

10 Epidemiologic Investigation of Infectious Disease Outbreaks Chesley L. Richards, Jr., and William R. Jarvis Centers for Disease Control and Prevention, Atlanta, Georgia

I. INTRODUCTION Infectious disease outbreaks in long-term care facilities (LTCFs) are common, can cause serious morbidity and mortality for residents, and can be time consuming to investigate and control. Epidemiologic investigation of these outbreaks can be as complicated as outbreak investigation in hospital settings, and yet fewer infection control resources are generally available in LTCFs. Despite these challenges, interdisciplinary infection control programs that include infection control professionals (ICPs), administrators, clinicians (e.g., physicians, nurse practitioners, physician assistants), pharmacists, laboratorians, and nursing staff can prevent many infectious disease outbreaks and successfully control those outbreaks that do occur. This chapter will review the principles of epidemiologic investigation as they apply to outbreaks in LTCFs, review aspects of selected infectious disease outbreaks, and discuss approaches to their prevention and control. Although LTCFs encompass a broad range of facilities from nursing homes for the elderly to long-term psychiatric facilities, the focus of this chapter is on outbreak investigation in nursing homes for the elderly. Many of the recommendations contained in the chapter, however, can be adapted and used in other LTCF settings. II. CHARACTERISTICS OF LONG-TERM CARE FACILITIES (LTCFs) Long-term care facilities are an increasingly important site of medical care and drug prescribing for the elderly. More than 40% of adults in the United States will 133

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spend some time in LTCFs before death, and the majority (53%) of residents in LTCFs will spend 1 year or longer (1,2). An important distinction between LTCFs and acute care facilities is that LTCFs are residential and persons in LTCFs are generally referred to as “residents” instead of as “patients.” Even though medical care is provided to LTCF residents, other aspects of a resident’s life take on greater importance than in acute care facilities. Socialization through group activities, both inside and outside the LTCF, is key to promoting good mental health for residents, although these activities may increase the risk of exposure to infectious agents, such as influenza. Group settings for eating and physical therapy, vital to the maintenance of resident independence and functional status, may increase risk for foodborne outbreaks, person-to-person transmission, or exposure to potential fomites, such as physical therapy equipment. Not surprisingly, the management of infectious disease outbreaks in LTCFs is complicated because the focus of LTCF care is on the preservation of physical function and socialization, not exclusively on diagnosis and treatment of infectious diseases. The availability of clinicians to evaluate febrile residents may be limited, and diagnostic studies, including microbiologic cultures, are generally less available than in acute care facilities. Consequently, nursing assistants usually perform the initial resident assessment, and licensed nurses relay important findings to clinicians, usually by telephone (3). In an effort to improve the evaluation of LTCF residents with fever or suspected infection, recommendations for the minimal evaluation of patients who develop fever in LTCFs were published recently (4). These guidelines specify tasks appropriate for nursing assistants and licensed nurses. In LTCFs, antimicrobials for the empiric treatment of suspected infection often are prescribed without onsite clinician evaluation or diagnostic testing (5,6). When diagnostic testing is performed, only limited tests are available in most LTCFs. This, together with outsourcing of most laboratory tests, may lead to suboptimal timeliness of reporting and, in some situations, inaccurate or misleading results. When residents are acutely ill or diagnostic testing is not available in LTCFs, residents often are transferred to the emergency departments of acute care hospitals. Not surprisingly, evaluation and management of infection accounts for approximately one-quarter of resident transfers from LTCFs to hospitals (7).

III. RISK FACTORS FOR OUTBREAKS IN LTCFs Risk factors for outbreaks include both resident and institutional factors (Table 1). The typical resident in an LTCF is female, older than 80 years of age, cognitively impaired, and living with several underlying medical conditions. Individual risk factors for infection include immunologic senescence, malnutrition, multiple chronic diseases, medications (e.g., immunosuppressants, central nervous system agents that diminish cough reflex), cognitive deficits that may complicate resident

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Table 1 Potential Risk Factors for Infectious Disease Outbreaks in Long-Term Care Facilities Resident level Decreased immunity to infection Malnutrition Chronic disease Functional impairment including diminished cough reflex, urinary incontinence, fecal incontinence, immobility Medications, especially psychoactive medications that diminish cough reflex and consciousness Invasive devices, such as urinary catheters, enteral feeding tubes, tracheostomies, etc. Institutional level Larger size (e.g., larger number of residents) Facility design (e.g., single versus multiple resident rooms) Group activities such as meals, physical therapy, recreational activities Low immunization rates Excessive antimicrobial use Widespread colonization of residents with antimicrobial-resistant organisms

compliance with basic sanitary practices (e.g., hand washing), functional impairments (e.g., fecal and urinary incontinence, immobility, diminished cough reflex), or invasive device use (e.g., urinary catheters, enteral feeding tubes, tracheostomies) (3,5,6,8). Institutional factors associated with increased risk for outbreaks are varied. Frequent group activities such as meals, physical therapy, recreational activities, or the common use of shared facilities (e.g., showers or whirlpool baths) increase the risk for outbreaks (3,5,6,8). Risk for outbreaks caused by specific pathogens (e.g., influenza, Streptococcus pneumoniae) is increased in settings where resident and healthcare worker immunization coverage is low. Finally, widespread excessive antimicrobial use and high rates of colonization with antimicrobial-resistant organisms increase the risk of outbreaks from these organisms. In a study of outbreaks among New York LTCFs, institutional risk factors for respiratory or gastrointestinal infection outbreaks included larger LTCFs (risk ratio 1.71 per 100 bed increase), LTCFs with a single nursing unit, or LTCFs with multiple units but shared staff (9). Risk for outbreaks was lower in LTCFs with paid employee sick leave. IV. KEY ASPECTS OF INFECTIOUS DISEASE OUTBREAK INVESTIGATION The epidemiologic investigation of infectious disease outbreaks in LTCFs should be conducted in a systematic fashion. Key components of the investigation are described below and are listed in Table 2.

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Table 2 Key Aspects of Outbreak Investigation in Long-Term Care Facilities 1. Have an infection control plan and program 2. Ask two important questions Is this surveillance artifact? Is an epidemiologic investigation needed? 3. Develop the case definition and line listing 4. Ascertain cases 5. Determine person, place, and time Host factors (person) Geographic assessment (place) The epidemic curve (time) 6. Develop preliminary hypotheses 7. Evaluate hypotheses Cohort and case-control studies Observational studies Microbiologic studies 8. Implement intervention(s) 9. Evaluate impact of intervention(s)

A. Infection Control Plan and Program Unlike hospitals, most LTCFs do not have substantial resources committed to infection control (10). Every infection control program should have an infection control plan outlining personnel, responsibilities, reporting relationships, and surveillance activities (see also Chapters 8 and 9). Designating a staff member as the “infection control person” is not sufficient; ideally, a trained, experienced ICP should be responsible for the program, either as a staff member at the facility or on a consulting basis. Knowing who is responsible within a facility for conducting surveillance and identifying, investigating, intervening, and reporting an outbreak is critical if the outbreak is to be identified and controlled as early as possible. Finally, establishing an infection control committee with active participation by the LTCF administrator, medical director, ICP, and nursing staff is important not only for support and guidance during an outbreak but for continued vigilance in optimizing infection control prevention efforts to avoid outbreaks. B. Is This Surveillance Artifact? An important first question to ask in a potential outbreak situation is whether the “outbreak” actually represents surveillance artifact (11). Common causes of surveillance artifact include (1) introduction of new infection definitions or surveillance methods; (2) a new ICP or inexperienced infection control staff; (3) new laboratory tests or populations; and (4) change in frequency of microbial cultures. For exam-

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ple, surveillance data may demonstrate a markedly increased rate of pneumonia in LTCF residents. This increase may represent a true outbreak; however, broadening the definition used for pneumonia or increasing the number of residents admitted with severe neurological impairment and frequent aspiration also may increase the rate of pneumonia without representing a true infectious disease outbreak. C. Deciding When to Conduct an Investigation The decision to conduct an epidemiologic investigation may be complicated and is generally driven by three situations: (1) identification of unusual infections or organisms with high potential for morbidity or mortality (e.g., a single case of meningococcal meningitis); (2) identification of organisms or infections that, although relatively common, have high risk for morbidity, mortality, and transmission to other residents (e.g., influenza, Norwalk virus); or (3) identification of epidemiologically important organisms (i.e., several cases of methicillin-resistant Staphylococcus aureus [MRSA] pneumonia). The definition for what constitutes an outbreak depends on the type of infection and, to some extent, the facility. If, for example, a single episode of a highly contagious, potentially lethal infection, such as meningococcal meningitis, is identified in an LTCF resident, an epidemiologic investigation and early, aggressive infection control interventions are necessary. In contrast, knowing when to call a cluster of several LTCF residents with acute respiratory infections or gastroenteritis an outbreak is more difficult. Generally, most authorities suggest that when the rate of infections is significantly higher than baseline endemic rates, an epidemic is occurring and an epidemiologic investigation is warranted (11,12). This definition depends on two factors to be helpful: the LTCF should have a surveillance system in place for detecting infections and calculating and comparing infection rates. More important, the LTCF should have a clinical staff member who understands basic principles of infection control and infectious disease epidemiology and is knowledgeable about changes in the LTCF’s resident population and infection trends in the facility. An important early consideration is whether and when to seek additional outside assistance to assist in the epidemiologic investigation. If the facility has a trained ICP, the initial investigation for most types of infectious disease outbreaks can be conducted and appropriate infection control interventions instituted by the ICP. If the facility lacks an ICP, then the clinical staff member charged with conducting the epidemiologic investigation may wish to seek assistance from an ICP or healthcare epidemiologist, a professional organization such as the Association of Professionals in Infection Control and Epidemiology (APIC) or the Society for Healthcare Epidemiology of America (SHEA), a state or local public health agency, or the Centers for Disease Control and Prevention (CDC). Regulations vary from state to state, but in general, LTCFs are required to report infectious disease outbreaks to local or state public health agencies.

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Table 3 Example of a Line Listing—Influenza Outbreak Case 1 2 3 4 5

Age

Sex

87 90 99 80 90

M F F F M

Ward/Room 4A 3A 2A 2A 2B

401 304 208 208 240

Onset

Cough

Fever

3/01/01 3/02/01 3/02/01 3/03/01 3/05/01

Yes Yes Yes Yes Yes

Yes No Yes No Yes

CXR Culture















Meals

Physical therapy

In room On ward Main dining room Main dining room Main dining room

Yes Yes Yes Yes Yes

Abbreviations: CXR, chest X-ray; M, male; F, female.

D. Case Definition and Line Listing Some challenges to conducting an epidemiologic investigation in an LTCF are unique; however, the basic approach to epidemiologic investigation is the same, whether the investigation occurs in a hospital or LTCF (11,12). The initial step in an investigation is usually a case review. When clinical staff or ICPs note increases in rates of infection, an unusual clustering of infections, or infections with unusual agents, all residents thought to fit in the cluster should be reviewed. The easiest tool for this review is a line listing containing demographic, clinical, and exposure information for each patient (Table 3). As early as possible, investigators should develop a tentative case definition. The case definition should include who, what, where, and when—a description of the infectious disease (what) along with three important parameters: person (who), place (where), time (when). For example, a case definition that could be used in a hypothetical pneumonia outbreak caused by influenza might include (see Table 4): Table 4 Example of a Case Definition—Influenza Outbreak What (Disease)

Person (Population) Place Time

Respiratory illness with at least two of the following symptoms/signs New or increased cough New or increased sputum production Fever (temperature 38°C) Pleuritic chest pain New or increased shortness of breath Respiratory rate 25 breaths per minute Worsening mental or functional status X-ray compatible with pneumonia Positive respiratory tract culture for influenza A Elderly residents Ward B of LTCF A. From January 1 to January 30, 2001

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If necessary, the initial case definition may be modified during the course of the investigation. For example, the above case definition might need to be changed in several ways: the definition of the respiratory illness might be made more general or specific, employees might be added to the population considered, the time frame might be broadened or narrowed, and additional wards in LTCF A might be considered. In general, the case definition should be changed judiciously; each change of the definition will affect the number of cases identified and modify results of comparative studies that are conducted during the course of the investigation. An alternative to changing the case definition completely is to modify the case definition to allow for “definite” cases and “possible/probable” cases. Using the example above, a “definite” case might be a resident with clinical symptoms and a positive respiratory tract culture for influenza A, whereas a “possible” case might be a resident with clinical symptoms but no culture or negative culture results. Although difficult, some attempt should also be made to identify the first case-patient (e.g., index case) especially if the presumed transmission is personto-person. By designating an index case, assumptions important to the investigation, such as incubation period and duration of the outbreak, can be made. As with the case definition, additional cases found during case ascertainment also may lead to a change in the designated index case. E. Case Ascertainment Case ascertainment should be as comprehensive as possible. Multiple sources of information and data are potentially available. Interviews with nursing staff, including nursing assistants, may be a quick way to ascertain cases; however, because many LTCFs experience rapid staff turnover and chronic understaffing, relying solely on what staff can recall may result in incomplete case ascertainment. Microbiology and radiology reports may be helpful, especially if the case definition includes results of these studies. In addition to chart review, existing infection control surveillance records may be helpful, especially in determining the endemic rate of infection. Because most LTCFs have a single pharmacy provider, antimicrobial prescription data may be a potential source to ascertain cases. Finally, medical records for residents transferred to hospitals may be another source for case ascertainment and to evaluate resident outcomes (e.g., death). F. Person, Place, and Time 1. Host Factors (Person) In addition to clearly defining the persons (or populations) affected by the infectious disease outbreak, investigators should review characteristics of case-patients on the line listing to identify specific host factors that may increase risk. The usual

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risk factors to be considered include intrinsic host factors (e.g., age, sex, race, underlying disease, nutritional status) and extrinsic factors (e.g., urinary catheters, feeding tubes, central vascular catheters, environmental exposures, receipt of medications, personnel exposure, food or nutritional product received). 2. Geographic Assessment (Place) Determining the geographic relationship between cases involved in the outbreak may be difficult and is influenced by a number of interrelated factors. Determining whether the cases occurred in a single area of the LTCF is critical. Using a spot map to identify the room of each case is important and usually can be made using a blueprint of the LTCF. Geographic clustering around a single living area may be readily apparent. In contrast, identifying common facilities (e.g., dining rooms, shower/bath facilities) that may be shared by residents from different parts of the LTCF may be both more subtle, yet more productive in some outbreak investigations in which a geographic pattern is not readily apparent. If the outbreak is believed to be due to an airborne or water borne organism, reviewing ventilation or plumbing diagrams may be helpful. 3. The Epidemic Curve (Time) The epidemic curve is a simple graphical tool using information from the line listing to display the time relationship of cases in the outbreak. Epidemic curves generally display time on the horizontal axis and number of cases on the vertical axis. Epidemic curves have some important features; first, the time axis should be shorter than the presumed incubation period of the infection. Secondly, the time period should include both the pre-epidemic (e.g., time before the index case) and epidemic periods. The shape of the epidemic curve is important. An abrupt rise in cases is suggestive of a point source for the outbreak (e.g., contaminated product or food). A more prolonged series of cases suggests person-to-person transmission. On some occasions, the epidemic curve may have features of both modes of transmission, suggesting that transmission may be occurring by several routes. G. Preliminary Hypotheses Once an initial set of cases is identified, an attempt should be made to generate hypotheses about what may be causing the outbreak. Sometimes, with a distinct cluster in time and space and an obvious source, quick action can be taken. More often, several potential sources and modes of transmission may be suggested by the preliminary data. At a minimum, hypotheses about the potential sources and the potential mode of transmission are needed to properly design comparative studies (described below). Once hypotheses are developed, comparative studies can be

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designed and used to test the hypotheses, with the aim of identifying the most likely causative factors for the outbreak. H. Studies 1. Cohort and Case-Control Studies Two types of comparative studies are generally used in outbreak investigations to identify risk factors for the outbreak: cohort or case-control studies (11,13). In cohort studies, all members of a defined population (i.e., cohort) are evaluated. The data can be collected retrospectively or prospectively. In cohort studies, relative risk, a quantitative measure of the strength of association between the exposure and the risk of developing the adverse condition, can be calculated; this quantitates the strength of association between the presumed exposure and the event. The primary advantage of cohort studies is that the whole population is assessed; bias through the process of selecting controls is not introduced. The primary drawbacks to the cohort design are that the appropriate population may not be defined, and cohort studies require significantly more resources to complete, especially if the frequency of cases is low. In case-control studies, known cases are compared to selected control residents. Selecting appropriate controls is important. It usually is advisable to randomly select controls from the population affected. Confounding may be a concern and can be controlled by using stratification or multivariate analyses. In some case-control studies, cases and controls may be “matched” on a particular characteristic, especially if a particular group of residents appears to be at significantly greater risk (e.g., only females are affected or only individuals in a particular wing of the LTCF). However, variables on which controls are matched cannot then be analyzed as risk factors. The advantage of case-control studies is that, especially with low frequency events or outbreaks occurring over a long period, the resources needed to collect data (e.g., chart reviews, microbiologic reviews, etc.) will be less than with a cohort study. In case-control studies, odds ratios are calculated and represent approximations of relative risk. Odds ratios indicate whether cases are more likely to have been exposed to a risk factor than controls. 2. Observational Studies Often, outbreaks may involve suboptimal compliance by healthcare workers with facility policies and procedures (i.e., hand hygiene, food preparation, sanitation) (11). Observational studies in which ICPs actually observe compliance with these procedures may be an important part of the overall epidemiologic/investigation. Before observation, infection control personnel should review policies and procedures with administrative personnel and identify changes or modifications that have occurred. The actual observations should occur for short periods (i.e., 1 hour)

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on all shifts and in locations where both case- and non-case patients reside, especially if within a facility there are areas of high attack rate and other areas with few or no cases. It is important that observers have a clear understanding of what constitutes the indication for a particular procedure and what constitutes failure to comply. For example, in an observational study on hand hygiene, the observer must know if hand hygiene is expected to occur before a patient encounter, before the healthcare worker leaves the patient room, or before another resident or patient care device is touched. 3. Microbiologic/Studies In outbreak investigations, microbiologic studies should be based on epidemiologic/findings. In addition to identification of bacteria or viruses from case-patient clinical specimens, several potential microbiologic studies may be considered, depending on epidemiologic results. First, in outbreaks where colonization may play an important role (e.g., antimicrobial-resistant bacteria), culture surveys of residents or healthcare workers may be useful. Important considerations include determining the best methods for culture collection, planning for the number of cultures or site of cultures, laboratory support for rapid processing of specimens, consistency of obtaining specimens, and appropriate record-keeping to correctly identify the resident or healthcare worker, site of culture, and type of specimen. Environmental cultures alone should be considered in situations in which the presumed pathogen and the epidemiologic findings suggest an environmental source. Widespread culturing of residents, healthcare workers, or environment before the epidemiologic investigation is not recommended and may often lead to erroneous conclusions about the outbreak. Furthermore, such widespread culturing is burdensome on personnel, costly and, often in the absence of epidemiologic direction, fails to identify the outbreak source. I. Implementing Interventions Once risk factors and potential sources are identified, interventions to terminate the outbreak should be instituted. These interventions must be fully discussed with the LTCF administrator, nursing director, medical director, and healthcare staff. Implementation of the interventions depends on support and acceptance by the staff. Especially in large, explosive outbreaks, some interventions, such as cohorting infected and colonized residents, institution of facility-wide vaccination of residents or healthcare workers, or increased glove use may be easily understood and accepted by staff. However, in longer duration, lower intensity outbreaks, acceptance may be suboptimal for interventions (e.g., improved compliance with hand hygiene, changes in food preparation policies, etc.), and more focus on education and training may be necessary. In these situations, incorporating ongoing

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process measurement of the intervention (e.g., observational study of hand hygiene among nursing assistants) with feedback periodically to staff may help to increase compliance with the intervention.

V. SELECTED INFECTIOUS DISEASE OUTBREAKS Examples of the more common types of infectious disease outbreaks that occur in LTCFs are presented below. The reader should also refer to other chapters devoted to these specific infections. A. Respiratory Tract Infections Outbreaks of respiratory tract disease in LTCFs are relatively common. In a recent report from five Canadian LTCFs, 16 outbreaks involving 480 of 1,313 residents were reported, occurring year-round with no seasonal predilection (14). The most common symptoms among residents during these outbreaks were cough (83%), fever (40%), and coryza (45%), and a minority (15%) of residents developed pneumonia. The most common pathogens included influenza, parainfluenza, or respiratory syncytial viruses; Legionella spp; or Chlamydia pneumoniae. Approximately 12% of residents were transferred to hospitals and 8% died. 1. Influenza The most important cause of respiratory tract disease outbreaks in LTCFs is influenza (see Chapter 13). Outbreaks of influenza A or B usually occur from early October to April but may sometimes extend into summer. Of the 20,000 deaths from influenza each year, 90% occur in persons aged 65 and older (15). Recent reports exemplify important aspects of influenza in LTCFs. In a report of an outbreak of influenza A affecting 68 residents, the LTCF had four separate buildings, one of which was newly constructed (16). Interestingly, the attack rate in the new building was significantly lower than the other buildings. Key differences in the new building included: (1) a ventilation system that did not recirculate air, (2) more public space per resident, and (3) no office space in the building serving the entire facility. Even widespread use of immunization, the cornerstone of influenza prevention, may be insufficient to prevent some LTCF outbreaks (see Chapter 20). In an LTCF with high rates ( 85%) of resident influenza vaccination, outbreaks involving 172 residents were reported despite a match between the vaccine strain and outbreak strain (17). Especially in older residents, influenza vaccine effectiveness may be diminished, increasing the risk for influenza outbreaks (18). These failures may be secondary to poor immunologic response to the vaccine in this elderly population. When influenza outbreaks do occur, chemoprophylaxis

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with antiviral agents such as amantadine, rimantidine, zanamivir, or oseltamivir should be considered in order to minimize morbidity and mortality (see Chapter 13). Prophylaxis should be given for 14 days or until 7 days after the onset of the last confirmed influenza infection in residents or staff (19). A recent review provides excellent detail on the use of specific antivirals for influenza prophylaxis (20). In a recent LTCF outbreak of amantidine-resistant influenza A, acceptance of inhaled zanamivir for chemoprophylaxis was high (92%), although 22% of the 128 treated residents had difficulty with the inhalations; this was especially true among residents who were fully dependent for activities of daily living (58%) (21). In the 2 weeks after chemoprophylaxis, no new infections occurred and no side effects were identified among zanamivir-treated residents. 2. Other Respiratory Viruses In addition to influenza, infections with parainfluenza virus, respiratory syncytial virus (RSV), adenoviruses, and rhinoviruses can cause respiratory tract disease in LTCF residents (see Chapter 13). Parainfluenza virus type 3 was associated with an outbreak of respiratory disease on a 50-bed nursing unit of a large Wisconsin LTCF. The attack rate was 50% and resulted in 16% mortality within 9 days of symptom onset (22). In contrast, a study of 30-day mortality suggested that noninfluenza viruses have lower mortality than influenza viruses, with mortality ranging from 6.1% (influenza B) and 5.4% (influenza A) to virtually nil for Respiratory Syncytial Virus (RSV) and rhinoviruses (23). The key observations from reports on respiratory tract outbreaks are that early identification of the infectious agents, institution of appropriate treatment or prophylaxis, and aggressive use of infection precautions, especially isolation of residents and improved healthcare worker compliance with hand hygiene recommendations, are critical to minimize serious morbidity and deaths. 3. Streptococcus pneumoniae Although not a common cause of outbreaks in LTCFs, Streptococcus pneumoniae is the most common pathogen identified in endemic respiratory tract disease in LTCF residents, is an important cause of invasive disease, and is increasingly resistant to antimicrobials. In a recent review of 26 S. pneumoniae outbreaks since 1990, the majority occurred in elderly patients in LTCFs or hospitals (24). The most common serotypes identified in these outbreaks were 23F, 14, and 4, all of which are included in current formulations of the pneumococcal vaccine. Recent outbreaks of S. pneumoniae pneumonia and bacteremia in Oklahoma, Massachusetts, and Maryland LTCFs were associated with low pneumococcal vaccination rates (25,26) (see Chapter 20). An LTCF outbreak of S. pneumoniae pneumonia in Massachusetts was associated with a 20% case-fatality rate. Antecedent infection with human parainfluenza virus was associated with increased risk of S. pneumoniae infection (27).

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4. Legionnaire’s Disease Legionnaire’s disease, caused by Legionella pneumophilia, remains an important consideration during respiratory tract disease outbreaks. Outbreaks in both LTCFs and hospitals are generally associated with contaminated water systems. Several reports of persistence of L. pneumophilia in hospital water systems despite the use of various interventions have been published (28–30). An outbreak of Legionnaire’s disease caused by L. pneumophila serogroup 1 in a new LTCF illustrates that water system contamination can occur quickly and lead to outbreaks of Legionnaire’s disease (31). To identify these outbreaks earlier, clinicians and ICPs should maintain a high index of suspicion for Legionnaires’s disease and obtain the proper laboratory support for microbiologic testing to identify L. pneumophila. B. Gastrointestinal Infections Outbreaks of gastroenteritis and diarrhea in LTCFs are common and commonly include Eschericia coli, Salmonella spp., or enteric viruses (see Chapter 18). The usual mode of transmission for these outbreaks is foodborne or person-to-person transmission. In a 250-bed LTCF in Tennessee, 14% of residents developed gastronenteritis due to Salmonella hadar (32). Among the 244 healthcare workers, the attack rate was 27% in laundry workers, but only 3% in nursing staff and 4% in kitchen staff. The index case was probably a member of the kitchen staff, but the high attack rate among the laundry staff was probably secondary to inconsistent use of gloves and lack of protective clothing while handling increased volumes of soiled linen during the outbreak. In an Australian LTCF, 25 residents developed gastroenteritis caused by Clostridium perfringens contamination of pureed food (33). Apparently, once food was liquified, it was not reheated and subsequently became contaminated. Consequently, the authors recommended that pureed food be reheated to 70°C to inactivate potential contaminating pathogens before consumption. Outbreaks caused by viruses occur frequently in LTCFs. In Virginia LTCFs during 1 year, caliciviruses, including the Snow Mountain Agent, and other small round structured viruses, were responsible for eight different reported outbreaks (34). In a Maryland LTCF with 121 residents, 51% of residents and 47% of the staff developed gastroenteritis because of a small, round-structured virus over a 4month period (35). The index case in the outbreak was a nurse who continued to work for 2 additional days after becoming ill. The outbreak illustrates the need to exclude ill employees in a timely fashion by providing sick leave and not expecting staff to take annual or vacation leave for illnesses. A Norwalk-like virus was responsible for an outbreak of gastroenteritis in a Washington LTCF. Among 91 residents, the majority (57%) developed acute gas-

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troenteritis after exposure to an ill LTCF resident, the index case (36). In the residents, prominent symptoms included vomiting (90%), diarrhea (70%), and fever (12%). Four residents required hospitalization and three died. Many healthcare workers (35%) also developed gastroenteritis. Based on molecular typing, the outbreak appeared to be among debilitated residents and the nurses caring for them, implying that it was propagated through LTCF staff rather than ambulatory residents. Cohorting of ill patients and strict adherence to infection control practices, such as hand hygiene, glove use, and barrier precautions, stopped the outbreak. C. Skin Infections Previous LTCF skin infection outbreaks include Streptococcus pyogenes-associated cellulitis, Pseudomonas aeruginosa associated with a contaminated whirlpool bath, group A Streptococcus, or antimicrobial-resistant organisms causing infections of pressure ulcers (6,37,38). Scabies is an important parasitic skin infection that not infrequently causes outbreaks in LTCFs (see Chapter 17). Transmission of scabies may occur by contact with mite-contaminated inanimate objects (e.g., bed linens) or direct person-to-person contact. Outbreaks of scabies in three Norwegian LTCFs lasted 5 months and involved 27 patients or healthcare workers (39). Initial treatments with permethrin were not successful; however, benzyl benzoate was effective. Ultimately, more than 600 residents and staff were treated. A key observation from these outbreaks was the need for simultaneous treatment of residents and staff and disinfection of bedding, clothing, and the environment. In France, oral ivermectin was used along with disinfection to successfully control an outbreak of scabies in 42 affected residents of a 128-bed LTCF (40). Ivermectin is not approved for use for scabies treatment in humans in the United States; however, this report illustrates a potentially useful oral therapy for scabies mass treatment. As with other outbreaks, early identification is optimal for management of scabies outbreaks and may occasionally require dermatological consultation or skin biopsy for diagnosis. D. Infections with Antimicrobial-Resistant Organisms (see Chapters 21 through 25) Recent reports suggest that antimicrobial-resistant pathogen outbreaks affect the elderly in both hospitals and LTCFs (6,41). Important antimicrobial-resistant pathogens include (MRSA); multiply resistant gram-negative bacilli such as E. coli, Acinetobacter, Enterobacter, or Pseudomonas aeruginosa; or vancomycinresistant Enterococcus (VRE) (42,43). Widespread colonization of residents in LTCFs with antimicrobial-resistant organisms provides a potential reservoir for subsequent transmission and outbreaks. In Chicago, a city-wide outbreak of multidrug-resistant Klebsiella pneumoniae and E. coli demonstrated that LTCFs were

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important reservoirs for antimicrobial-resistant organisms (41). Furthermore, in a single Chicago skilled nursing facility, 43% of residents were colonized with at least one antimicrobial-resistant organism (44). Recent studies have demonstrated success in reducing VRE colonization or infection and may offer important intervention strategies for the future (45,46). These studies have documented the importance of resident screening, isolation, healthcare worker hand hygiene, and decreased inappropriate antimicrobial use. In addition to cross-transmission, widespread antimicrobial use is a potential risk factor for the development of antimicrobial resistance within LTCFs. In Maryland, 8% of LTCF residents were documented to be receiving antimicrobial therapy at a given time, and over a year, 54% of residents received at least one course of antimicrobial therapy (47). In four New York LTCFs, the percentage of resident-days during which antimicrobials were given ranged from 2.7% to 6.8% (48). In a Veterans Affairs LTCF, the majority (54%) of resident febrile episodes resulted in the initiation of antimicrobial therapy, with upper respiratory tract illnesses, bronchitis/pneumonia, or urinary tract infections accounting for the majority of indications (49). After diagnostic evaluation, 39% of residents continued to receive antimicrobials despite negative laboratory and radiographic studies for bacterial infections. In general, previous studies have found substantial inappropriate use of antimicrobials in LTCF residents, ranging from 25% to 75% (50). Inappropriate antibiotic use adds to patient care costs, may place the patient at risk for adverse medication reactions, and increases the risk of colonization or infections with antimicrobial-resistant organisms (48,50).

VI. PREVENTION AND CONTROL OF OUTBREAKS The primary means to prevent and control infectious disease outbreaks in LTCFs include a well-organized infection control program, the timely use of recommended immunizations, and prudent use of antimicrobials (see also Chapters 8 and 9). A. Infection Control Several reviews, guidelines and position statements for infection control in LTCFs have been published previously (51–53). In addition, guidelines from CDC for many aspects of infection control are available through the internet (www.cdc. gov/ncidod/hip). The key components of a well-organized infection control program in LTCFs include: (1) an infection control professional (ICP) to head the program, (2) an infection control committee, (3) a written infection control plan, and (4) sufficient administrative support to undertake core infection control functions.

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The two most important aspects of an LTCF infection control program are that the ICP is trained in infection control and that the LTCF administrator provides support and resources for the program. In a survey of LTCFs in the northeastern United States, most ICPs were registered nurses (90%) who performed infection control duties on a partime basis (median  8 hours per week) (10). However, only half (52%) had formal training in infection control and most had additional clinical or administrative nursing duties. These sobering statistics point out the difficulty encountered in obtaining significant resources for LTCF infection control. However, the second component of the program, an infection control committee, can be instrumental in assisting the ICP in developing the infection control program. In smaller LTCFs, the committee may consist of the ICP, nursing director, medical director, and administrator. In larger LTCFs, the infection control committee also might include consultant pharmacists, an infectious disease expert, representatives from physical therapy or rehabilitation, and environmental services. The limited availability of diagnostic studies in LTCFs is a particular challenge for managing infectious disease outbreaks (4). Diagnostic studies, such as microbiology cultures, routine chemistry and hematologic tests, and radiologic studies seldom are available. Isolation facilities often are not available and may necessitate resident transfer to acute care facilities (4). Access to expert infectious disease consultation may be limited. Long-term care facility ICPs faced with an outbreak, but who have resource and expertise limitations, should seek assistance from their local and state health departments in a timely fashion. In addition, the formation of teams including both geriatric clinicians, ICPs, and nursing staff may be especially beneficial in outbreak management (54). Another important resource during outbreaks is the consultant pharmacist. During an influenza outbreak in a 570-bed nursing home facility, pharmacists assumed responsibility for educating families and patients about amantadine prophylaxis, providing individualized dosing, monitoring and evaluating adverse events, and handling drug distribution (55). Overall, acceptance of chemoprophylaxis was high (91%) and most of the 22 adverse reactions were resolved through dose reduction as opposed to drug discontinuation. B. Immunization Currently, LTCF residents should have yearly influenza vaccination and pneumococcal vaccination once after age 64 (56,57) (see Chapter 20). Overall vaccination rates among LTCF residents for influenza vaccine (64%) and pneumococcal vaccine (28%) are suboptimal and many LTCFs have inadequate policies addressing routine vaccination (58). To diminish the likelihood of an influenza outbreak, LTCFs should develop an active immunization program. The components of a well-organized immunization program include defining the facility’s policy on immunization, developing an implementation manual, training staff members in-

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cluding physicians on the plan, collecting and recording baseline vaccination rates for current residents, and then initiating vaccination of both current residents and new arrivals (16). To monitor for outbreaks and institute timely control measures, LTCF infection control personnel should include suveillance for acute febrile respiratory tract illnesses. Furthermore, LTCF personnel should develop the surveillance system in conjunction with local and state health departments to enhance communication and ensure compliance with public health requirements (16). Recently, implementation of standing orders for influenza and pneumococcal vaccination in LTCFs has been proposed as an effective intervention to increase vaccination rates (58). C. Antimicrobial Use and Isolation Precautions Antimicrobials are used frequently in LTCF residents and their use usually is initiated by telephone order. To minimize inappropriate antimicrobial use, recent recommendations include (1) monitoring clinicians’ use of antimicrobials, (2) establishing a formal antimicrobial review program, and (3) developing facility-specific antimicrobial use guidelines (50). Whether these interventions will reduce outbreaks with antimicrobial-resistant organisms remains to be proven (see Chapter 11). Transmission-based isolation precautions are recommended, effective, and widely used in hospitalized patients who are colonized or infected with selected antimicrobial-resistant organisms (59). Consistent national guidelines for the use of isolation precautions in LTCF residents with infections caused by antimicrobial-resistant organisms do not currently exist. Strict isolation and use of barrier precautions in colonized LTCF residents have not been shown to consistently reduce infections from antimicrobial-resistant organisms; however, glove use and good hand hygiene have been shown to be effective (52). Often with bed-bound residents, healthcare workers are the usual vectors for transmission of pathogens. Because good hand hygiene is vital to reduce cross-transmission, LTCFs should consider the use of newly developed, waterless, alcohol-based hand hygiene agents to promote hand hygiene. Decisions about isolation of LTCF residents colonized or infected with antimicrobial-resistant organisms must be considered on an individual resident and facility basis and must incorporate both an assessment of risk for cross-transmission and the impact on the resident’s social and psychological health (51–53).

VII.

CONCLUSIONS

Infectious disease outbreaks in LTCFs are an important public health concern, can result in serious illnesses and death in LTCF residents, and can be disruptive to

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LTCF staff. Most outbreaks are, at least in theory, preventable. The major patient risk factors include chronic illnesses, incontinence, and poor respiratory function. These risk factors may not be amenable to interventions. However, institutions can attempt to prevent outbreaks by ensuring residents receive appropriate immunizations, promote judicious use of antimicrobials, and ensure that the LTCF has a well-staffed and organized infection control program. Once infectious disease outbreaks occur, epidemiologic investigation of the outbreak should proceed quickly. The key components of the investigation should include developing a case definition, compiling a line listing of known case-patients, conducting additional case ascertainment, constructing an epidemic curve and geographic plots, and developing working hypotheses as to the source, mode of transmission, and possible organisms. The types of studies (e.g., case-control, cohort, observational, microbiologic) performed will depend on the available resources. Interventions to terminate the outbreak should be consistent with epidemiologic findings and be effectively communicated to administrators, staff, and public health officials. Over the next several decades, the population of elderly LTCF residents will grow dramatically; resources for infection control programs and outbreak prevention in the LTCF will be an important investment toward improving the quality of care in this increasingly important healthcare setting.

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11 An Approach to Antimicrobial Therapy Shobita Rajagopalan Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California

Jay P. Rho University of Southern California University Hospital, Los Angeles, California

Thomas T. Yoshikawa Charles R. Drew University of Medicine and Science and Martin Luther King, Jr.–Charles R. Drew Medical Center, Los Angeles, California

I. GENERAL ISSUES OF ANTIMICROBIAL THERAPY A. Clinical Relevance The overall approach to antimicrobial chemotherapy remains an important topic of practical and clinical significance. Antimicrobial agents are among the most widely prescribed drugs in long-term care facilities (LTCFs). An estimated one fifth of all LTCF residents receive an antimicrobial agent at any given time. Antimicrobial usage may seem disproportionately low compared to the 1.5 million infections observed in the long-term care setting annually (1), but indiscriminate prescribing of antimicrobial agents with lack of adequate documentation of infection, potential adverse drug reactions, and emergence of antimicrobial resistance are major concerns (2). Clinicians must thus exercise caution in their approach to antimicrobial prescription; vulnerable populations, for example elderly persons residing in LTCFs, need particular consideration because of the additional increased morbidity and mortality associated with age-related decline in immune function, debility, and comorbid illnesses (diabetes mellitus, cerebrovascular accidents, alcoholism, malnutrition, etc.). There should be a rational approach to an155

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timicrobial prescribing in residents of LTCFs, with focus on age-related physiologic, pharmacokinetic, and pharmacodynamic changes that can affect the selection and dosing of such chemotherapeutic agents. B. Assessment of Antimicrobial Use in LTCFs Significant data evaluating the appropriateness of the therapeutic utility of antimicrobial agents in LTCFs suggest that a substantial proportion of antibiotic treatments are often initiated in the absence of important diagnostic information, such as the presence of fever, leukocytosis, or culture information (3–5). One study surveying 42 nursing homes and 11 affiliated intermediate care facilities suggested that systemic antibiotics were initiated in 62.4% of cases with inadequate initial diagnostic evaluation (6). Another study that included 3,899 residents from 52 nursing homes indicated that 22% of all antibiotics prescribed were unnecessary, that is, viral upper respiratory infection and asymptomatic bacteriuria (4). A similar study that focused on the usage pattern of a specific antibiotic, ciprofloxacin, in a long-term care setting found that only 25% of orders for that agent were appropriate and 23% were prescribed for inappropriate indications; 49% were considered inappropriate because of more effective and/or less expensive available alternatives (7). One study demonstrated that antibiotic prescribing for 282 elderly residents of an LTCF who received an antibiotic for a presumed urinary tract infection was inappropriate in 40% of cases; 222 (78.7%) cases, however, showed clinical improvement (8). Using a Medication Appropriateness Index (MAI) (9) to measure appropriateness of antibiotic prescribing, 113 antibiotics orders (39.7%) were considered inappropriate. The three antibiotics most often inappropriately prescribed were ciprofloxacin (too expensive), trimethoprim-sulfamethoxazole (TMP-SMX) (incorrect duration), and nitrofurantoin (improper dosage). In addition, inappropriate prescribing accounted for an additional $560 per day in treatment costs.

II. OPTIMIZING THE USE OF ANTIMICROBIAL AGENTS IN THE LTCF The optimal use of antimicrobials in LTCFs remains problematic largely because of a delay in the diagnosis and initiation of appropriate treatment of infections. Typical manifestations of infection, such as fever, may be absent or blunted in many elderly patients with serious or life-threatening infections (10,11) (see Chapter 6). Limited availability of laboratory and radiological data may, in addition, preclude a precise diagnosis. General principles for initiating antimicrobial therapy are described in Table 1.

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Table 1 Approach to Antimicrobial Prescribing in Long-Term Care Facilities 1. Not all clinical or functional changes in LTCFs residents should be attributed to infections. 2. Antibiotics should be administered only when there is potential clinical benefit. For example, studies have clearly shown that both men and woman residing in LTCFs derive no benefit from treatment of asymptomatic bacteriuria. 3. Chronic suppressive therapy with antibiotics or antimicrobial chemoprophylaxis should be restricted unless there is documented evidence of clinical efficacy and therapeutic benefit. 4. Continuation of antibiotic therapy beyond standard recommended periods should be discouraged. For example, catheter-related urosepsis should be treated until clinical sepsis is improved but should not be continued in an attempt to maintain sterile urine. 5. In circumstances in which a specific pathogen is isolated and antibiotic sensitivity studies are available, the initial broad-spectrum antibiotic should be changed to a more narrowspectrum agent, if the organism is susceptible to such an agent. Abbreviation: LTCF, long-term care facility.

A. Minimum Criteria for Initiation of Antibiotics Minimum criteria for initiating systemic antibiotics for bacterial infections have been proposed by a consensus group of physicians, geriatricians, microbiologists, and epidemiologists (12). These criteria were developed to provide guidelines for the appropriate initiation of empiric antibiotics in clinically stable LTCF residents; critically ill patients with sepsis or sepsis syndrome necessitating transfer to an acute care facility were not included. Empirical regimens for common infections found in LTCF residents such as skin and soft-tissue infections, respiratory infections, and urinary infections, as well as fever of unknown origin were outlined (Table 2). Other potential infections, such as intravenous catheter-related infections or infections of mucous membranes and conjunctivae; topical antibiotic use; use of antiviral and antifungal agents; prophylactic antibiotics; and chronic suppressive antibiotics were not addressed. Prospective assessment of these guidelines for appropriate antibiotic use has not been analyzed. B. Empirical Antimicrobial Therapy An empirical antimicrobial regimen should be directed against the most likely pathogens and able to achieve the desired therapeutic concentrations at the suspected site of infection. The choice of a specific empirical antimicrobial regimen should be based on the severity of the patient’s illness, the nature of underlying diseases, prior exposures to antimicrobials, and history of drug allergies. The Society of Healthcare Epidemiology of America (SHEA) has published a position paper on antimicrobial use in LTCFs that provides recommendations for empiri-

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Table 2 Minimum Criteria for Initiation of Antimicrobials in Long-Term Care Facilities Skin and soft tissue infections Either new or increasing purulent drainage at a wound, skin, or soft tissue site, or at least two of the following: 1. Fever (temperature 37.9°C [100°F] or and increase of 1.5°C [2.4°F] above baseline temperatures taken at any site 2. Redness 3. Tenderness 4. Warmth 5. Swelling that was new or increasing at the affected site Respiratory infections 1. If the resident is febrile with a temperature 38.9°C [102°F], at least one of the following: (1) respiratory rate 25 breaths per minute (2) productive cough 2. If the resident has a temperature 37.9°C [100°F] or 1.5°C [2.4°F], increase above baseline temperature, minimum criteria for initiating antibiotics requires presence of cough and at least one of the following: (1) pulse 100/minute (2) delirium (3) rigors (shaking chills) (4) respiratory rate 25/minute 3. For afebrile residents known to have COPD, classified as high-risk because of age  65, minimum criteria for initiating antibiotics for a suspected respiratory infection include a new or increased cough with purulent sputum production. 4. For afebrile residents who do have COPD, minimum criteria for initiating antibiotics include a new cough with purulent sputum production and a least one of the following: (1) respiratory rate 25 breaths per minute (2) delirium Urinary tract infection 1. For residents who do not have an indwelling catheter, minimum criteria for initiating antibiotics include acute dysuria alone or fever ( 37.9°C [100°F] or 1.5°C [2.4°F] increase above baseline temperature) and at least one of the following: (1) new or worsening urgency (2) frequency (3) suprapubic pain (4) gross hematuria (5) costovertebral angle tenderness (6) urinary incontinence

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Table 2 (Continued) 2. For residents who have a chronic indwelling catheter (either an indwelling Foley catheter or a suprapubic catheter), minimum criteria for initiating antibiotics include the presence of at least one of the following: (1) fever (37.9°C [100°] or 1.5°C [2.4°F] increase above baseline temperature) (2) new costovertebral tenderness (3) rigors (shaking chills) with or without identified cause (4) new onset of delirium Fever in which the focus of infection is unknown Presence of fever ( 37.9°C [100°F] or 1.5°C [2.4°F] increase above baseline and at least one of the following: (1) new onset of delirium (2) rigors Abbreviation: COPD, chronic obstructive pulmonary disease. Source: Ref. 12.

cal antimicrobial therapy for the most frequent types of infections in nursing home residents including upper and lower respiratory tract infections, urinary tract infections, skin and soft-tissue infections, urinary tract infection, skin and soft-tissue infections, diarrhea, and fever of unknown origin (13) (Table 3). (See also specific chapters on each of these infections). The common cold, pharyngitis, and sinus infections are the most frequent infections of the upper respiratory tract. Because the vast majority of upper respiratory tract infections are viral in etiology, empirical antibiotic therapy is seldom indicated. However, if a throat culture or a reliable streptococcal screening test documents the presence of group A streptococci, penicillin would be the drug of choice. For acute bacterial sinusitis, first-line therapy includes any of the following antibiotics: trimethoprim-sulfamethoxazole, amoxicillin, and cefuroxime axetil. The selection of amoxicillin-clavulanic acid for acute bacterial sinusitis should be reserved for patients who respond poorly to treatment with one of the first-line antibiotics. C. Antimicrobial Utilization Review Promoting the optimal use of antimicrobials in LTCFs requires diligent antimicrobial utilization review. Surveillance and control activities are the major foci of these programs. Antimicrobial utilization is logically within the purview of the infection control program. Infection control programs traditionally have advocated education, isolation techniques, and hand washing to control nosocomial infections; however, they now are beginning to address problems of antimicrobial use. A recent survey found that more than one half of LTCFs had an antimicrobial utilization program (14).

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Table 3 Empirical Antimicrobial Therapy for Common Infections Clinical syndrome Upper respiratory infection Coryza/common cold Pharyngitis Sinus infection

Lower respiratory infection Acute bronchitis Acute exacerbation of chronic bronchitis Pneumonia

Urinary tract infection Skin/soft tissue Cellulitis Infected pressure ulcer*

Candidiasis Diarrhea Clostridium difficile Salmonella, Shigella Escherichia coli O157:H7

Empiric antimicrobial None None; treat only if group A Streptococcus TMP-SMX
amoxicillin, cefuroxime axetil, macrolide; second line: amoxicillin-clavulanic acid, quinolone Most cases viral, no antibiotics indicated Amoxicillin, TMP-SMX, doxycycline TMP-SMX, amoxicillin, cefuroxime axetil, macrolide, doxycycline; second line: amoxicillin-clavulanic acid, quinolone, clindamycin (aspiration pneumonia) TMP-SMX, quinolone, aminoglycoside (parenteral) Dicloxacillin: second line: cephalexin, clindamycin Metronidazole or clindamycin and TMP-SMX or quinolone; amoxicillin-clavulanic acid Topical antifungal Metronidazole TMP-SMX, quinolone None

Abbreviation: TMP-SMX, trimethoprim-sulfamethoxazole. * May require surgical debridement; if severe systemic symptoms, initial parenteral therapy should be considered. Source: Ref. 12.

D. Adverse Drug Events Approximately 350,000 adverse drug events, 20,000 of which are fatal, occur each year among the 1.5 million residents of LTCFs in the United States (15). Studies that have evaluated the patterns and quality of medication prescribing in nursing homes (15,16) have found antimicrobials to be among the most frequently implicated drugs in causing adverse drug events. In a study of 18 community-based nursing homes located in eastern Massachusetts encompassing 28,839 nursing home resident-months, 546 adverse drug events (1.89 per 100 resident-months)

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and 188 potential adverse drug events (0.65 per 100 resident-months) were identified (15). Overall, 51% of the adverse drug events were judged to be preventable, including 171 (72%) of the 238 fatal, life-threatening, or serious events and 105 (34%) of the 308 significant events. Antibiotics were associated with 36% of nonpreventable adverse drug events, but fewer than 5% of the adverse drug events were considered preventable. The majority of adverse drug events associated with antibiotics were rashes and confirmed Clostridium difficile diarrhea. Clinicians should be aware that adverse drug events occur more frequently in frail elderly and, therefore, a systematic examination of adverse events to identify risk factors should be undertaken. E. Cost of Inappropriate Use of Antimicrobial Agents The consequences of inappropriate use (or overuse and misuse) of anti-infective agents and resultant financial implications include exposing patients to the potential risk of adverse drug reactions, selection of resistant bacteria, and high rates of nosocomial infections—all of which will increase healthcare costs (17,18). The total cost of inappropriate prescribing of antimicrobials can only be grossly estimated. These agents are among the most costly of all drugs prescribed in the United States, accounting for sales between $3 to 4 billion (18). If a quarter of all prescriptions for anti-infective agents are considered inappropriate for various reasons, this could account for an additional annual cost to the healthcare system of $1 billion. Further, the increased costs of treating adverse drug reactions, infections, and their complications resulting from drug resistance also have to be considered. Because the geriatric population is becoming the highest user of healthcare services and the largest consumers of drugs, it is essential that a rational approach to prescribing drugs for the elderly, including antimicrobial agents, be emphasized.

III. DRUG FACTORS TO CONSIDER IN PRESCRIBING ANTIMICROBIAL THERAPY Once an antimicrobial agent is selected on the basis of known or anticipated activity against the pathogen(s), the goal of therapy is to deliver that drug to the site of infection in concentrations sufficient to inhibit or kill the organism(s). Most serious infections require antibiotic concentrations to exceed the minimum inhibitory concentration (MIC) of the infecting organism at the site of infection. Some drugs, such as aminoglycosides and fluoroquinolones, exhibit concentration-dependent antimicrobial effects, with high drug concentrations exerting more rapid bactericidal action and longer post antibiotic effects (PAE) than lower concentrations. The elderly undergo age-related physiologic changes that directly influence the dispo-

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sition and efficacy of various antimicrobial agents (19). The progressive decrease in the ability of vital organ systems of the elderly to maintain homeostasis can lead to alterations in drug clearance and drug receptor sensitivity. A. Pharmacokinetics Pharmacokinetics describes the fundamental mechanics of drug movement through the body over time, including factors that describe the absorption, distribution, metabolism, and elimination, or the overall fate of a drug in vivo (20). A summary of age-related physiological changes are shown in Table 4 (20,21). 1. Absorption Age-related changes in the gastrointestinal tract may influence drug absorption. A decrease in gastric acid secretion and an increase in gastric pH are associated with the aging process. The absorption of antimicrobials that are dependent on increased acidity (e.g., sulfonamides, ketoconazole) may be decreased, whereas drugs that are degraded in an acidic environment will have greater bioavailability. The significance of these changes is generally minimal and rarely affects dosing requirements. 2. Distribution Age-related changes that can affect the distribution of drugs include changes in body composition and cardiac output. In the elderly, the ratio of body fat to total Table 4 Physiological Changes Associated with Aging Pharmacokinetic parameter Absorption

Distribution

Elimination

↓  decrease activity or function. ↑  increase activity or function. ↑↓  no increase or decrease activity or function.

Physiological change with aging ↓Gastric emptying ↓Gastric acidity ↓Gastrointestinal motility ↓Absorptive surface ↓Lean body mass ↑Body fat ↑Serum 1-acid glycoprotein ↑↓Enzyme activity ↓Hepatic (liver) blood flow ↓Renal (kidney) blood flow ↓Glomerular filtration rate ↓Tubular secretion

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body water is increased compared with younger individuals. A decrease in lean body mass, coupled with a decrease in total body water, is associated with a decreased volume of distribution for water-soluble drugs. Thus, with older adults, antimicrobials that are distributed primarily in body water or lean mass may have higher blood concentrations than in younger adults, which can lead to potential toxicity. Conversely, in the elderly, lipid-soluble drugs have a greater body fat distribution, which may reduce blood concentrations and lead to potential subtherapeutic blood concentrations. 3. Metabolism Age appears to have no effect on the functional activity of various cytochrome P450 isoenzymes either in terms of in vitro protein content, immunohistochemical content, or in vivo enzyme activity for older patients as compared to younger patients. 4. Clearance Age-related changes in renal function are probably the most significant contributors to alteration in drug clearance. Reduction in kidney mass, renal blood flow, and the subsequent number of functioning nephrons, glomerular filtration rate, and the rate of tubular secretion accounts for the decreased renal excretory capacity observed with aging (20,21). Diminishing renal function and lack of compensatory increases in nonrenal clearance in elderly patients have been associated with prolongation of the serum half-lives of beta-lactams, aminoglycosides, glycopeptides, sulfonamides, and fluoroquinolones. B. Tissue Penetration Some drugs, such as aminoglycosides, macrolides, and fluoroquinolones bind extensively to certain tissue components. Intracellular accumulation of aminoglycoside is slow, however, because of its poor membrane permeability. Intracellular aminoglycoside concentrations tend to be low after initial drug exposure but are high after more sustained exposure and multiple dosing. However, the drug is microbiologically inactive in an acidic environment, such as in the phagolysosome. Indeed, the high intracellular aminoglycoside concentrations achieved in the renal cortex after multiple doses may be the cause of their nephrotoxicity. C. Pharmacodynamics Pharmacodynamics refers to the action of drugs or the biological effects resulting from the interaction of a drug and its receptor site. Pharmacodynamics describes the antimicrobial effect at the site of infection as well as toxic effects in relation to the concentrations of the antimicrobial drug during the course of drug therapy.

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For drugs with concentration-dependent bactericidal activity, such as aminoglycosides and fluoroquinolones, the rate and extent of bactericidal action increase with increasing drug concentrations above the minimum bactericidal concentration (MBC) up to a point of maximum effect, usually 5 to 10 times the MBC. In addition, the duration of the PAE is concentration-dependent with these drugs, with longer PAEs induced by higher drug concentrations. In contrast, the bactericidal activity of most beta-lactam antibiotics against gram-negative bacilli is relatively slow and continues as long as the concentrations are in excess of the MBC. It does not increase as the drug concentration is increased, that is the bactericidal action of beta-lactams is time-dependent and not concentration-dependent. For time-dependent agents that exhibit short or no postantibiotic intervals—such as extended-spectrum beta-lactams effective against most gram-negative bacilli—multiple, small, frequent doses or continuous intravenous infusion produces similar or superior bactericidal effects compared with infrequently administered larger doses.

IV. POTENTIALLY USEFUL AND SAFE ANTIMICROBIAL AGENTS FOR LTCF RESIDENTS The vast majority of common bacterial illnesses in LTCF residents respond promptly to broad-spectrum oral antibiotics, but parenteral therapy is occasionally necessary for more severe infections. Some LTCFs have the capacity to provide parenteral therapies. There are antibiotics that may be administered via the intramuscular route, for example select third-generation cephalosporins such as ceftriaxone that, when administered intramuscularly, demonstrate similar efficacy compared with the intravenous injection. In addition several antibiotics, such as quinolones, have oral formulations that achieve systemic concentrations comparable to a parenteral route (22). Such advances should mitigate the need for transfer of LTCF residents to an acute care facility for mild to moderate or uncomplicated infections (23). A. Aminoglycosides Aminoglycosides in the elderly must be prescribed with caution because of the well-described risks of enhanced ototoxicity and nephrotoxicity associated with these agents and the availability of safer and less toxic drugs with comparable spectra (i.e., cephalosporins, monobactams, carbapenems, beta-lactam/beta-lactamase inhibitor combination antibiotics, and quinolones). However, these agents are rapidly bactericidal against staphylococci and gram-negative aerobic bacteria, including Pseudomonas sp, and often provide synergy with other agents (e.g., beta-lactams) for treatment of serious or life-threatening infections such as enterococcal endocarditis (24). Renal impairment (generally reversible) and ototoxic-

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ity (generally irreversible) are the two most common and important potential adverse effects of these antibiotics (25). Because plasma half-life is increased in patients with decreased renal function (most elderly persons), the dose should be reduced on the basis of the creatinine clearance. Nephrotoxicity is less likely with once-daily dosing compared with the conventional every 8-hour dosing and is usually reversible (26). Nephrotoxicity, however, may lead to high serum levels of aminoglycosides, which can cause irreversible ototoxicity. Risk of ototoxicity increases with age and is highest in patients with pre-existing hearing deficiencies. Thus, aminoglycoside use in older LTCF residents should be reserved for those with serious or life-threatening infections that require hospitalization and are caused by pathogens susceptible to aminoglycosides (27). B. Beta-Lactams Select beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors) may be useful in the management of infections in LTCFs because of their broad spectrum, favorable pharmacokinetics and favorable safety profiles. These would include parenteral cefotetan, ceftriaxone, cefoperazone, and cefipime, as well as oral agents such as penicillin, dicloxacillin, amoxicillin, amoxicillin-clavulanate, cephalexin, cefuroxime axetil, and cefixime (27). C. Macrolides Erythromycin, clarithromycin, and azithromycin have a limited role in the management of infections in the elderly in general. Clarithromycin and azithromycin have more favorable dosing regimens, improved antimicrobial activity, and lower gastrointestinal intolerance compared with erythromycin. These agents are moderately active against most strains of streptococci, methicillin-sensitive Staphylococcus aureus, anaerobes, Moraxella catarrhalis, Haemophilus influenzae, Legionella, Mycoplasma pneumoniae, and Chlamydia pneumoniae, as well as atypical mycobacteria such as Mycobacterium avium complex. Limited data are available regarding pharmacokinetics of these newer macrolides in elderly persons; decrease in drug clearance has been attributed to reduce renal clearance. The indications for the newer macrolides in elderly LTCF residents are no different than for the general population. Although macrolides have been recommended in community-acquired pneumonia treated in an ambulatory setting (28), their role as therapy for nursing home-acquired pneumonia is unclear (29). D. Clindamycin This agent is commonly used for anaerobic and staphylococcal infections and for life-threatening group A beta-hemolytic streptococcal infections (streptococ-

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cal toxic shock syndrome, necrotizing fasciitis), the latter necessitating acute care facility transfer. Residents of LTCFs are particularly susceptible to antibiotic-associated colitis caused by C. difficile; clindamycin use is a relatively common association. The drug has utility in the LTCF for treating mild to moderate infections such as skin and soft tissue infections, including infected pressure ulcers, oral and dental infections, and respiratory tract infections caused by susceptible bacteria. E. Fluoroquinolones The fluoroquinolones are a group of synthetic antibiotics that have a broad spectrum of antimicrobial activity, good absorption from the gastrointestinal tract, a unique mechanism of action (inhibition of bacterial topoisomerases), favorable pharmacokinetic properties, and a good safety profile (30). As a group, the fluoroquinolones have excellent in vitro activity against a wide range of gram-positive bacteria and many gram-negative bacteria such as Enterobacteriaceae and Aeromonas, Brucella, Campylobacter, Haemophilus, Legionella, Moraxella, Neisseria, and Vibrio. These agents are active against Pseudomonas aeruginosa but are significantly less active against other pseudomonal species, including P. capacia and P. fluorescens. Ciprofloxacin is the most active quinolone against P. aeruginosa. The newer generation fluoroquinolones have activity against gram-positive bacteria including Streptococcus pneumoniae and staphylococcal species, i.e., methicillin-sensitive S. aureus (MSSA) and coagulase-negative species. The fluoroquinolones have less activity against streptococcal species and enterococci. These agents in general have very poor activity against anaerobes and Nocardia organisms. Ciprofloxacin and ofloxacin are active in vitro against Chlamydia trachomatis, C. pneumoniae, Mycoplasma hominis, and M. pneumoniae. Ciprofloxacin and ofloxacin are active against many species of Mycobacterium, including M. tuberculosis, M. kansasii, M. fortuitum, and M. xenopi. Cipro-floxacin initially was introduced to North America in 1987. Since its release, it has been widely used in LTCFs (22). These agents are used because they allow the convenience of oral therapy with an agent with good bioavailability, are easily administered by once- or twice-daily dosing, are perceived to be safe, and have wide spectrum of activity. In the elderly, quinolones are useful in the treatment of complicated urinary tract infections, bacterial prostatitis, skin and soft tissue infections, pneumonia, malignant external otitis, and bacterial diarrhea caused by susceptible pathogens (22). The newer generation fluoroquinolones (e.g., levofloxacin, gatifloxacin, moxifloxacin) with improved gram-positive (including S. pneumoniae) activity over that of the older agents in this class are now considered agents of choice for the treatment of community-acquired pneumonia in adults, including the elderly (28). Adverse effects of quinolones in the elderly occur in 5%

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to 15% of cases, including gastrointestinal (nausea, vomiting, diarrhea) and central nervous system (dizziness, headache, insomnia) effects. Associated drug interactions with other medications include decreased theophylline clearance associated with increased serum levels of ciprofloxacin, but not norfloxacin or levofloxacin, and multivalent ions (e.g., calcium, iron, aluminum) contained in foods or drugs that significantly reduce absorption of quinolones from the upper gastrointestinal tract. With the intense quinolone use in many LTCFs, quinolone resistance of organisms has increased. Resistance via mutations in the genes encoding topoisomerase II and IV along with increased drug efflux is common in clinical isolates. Quinolone resistance (methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, S. pneumoniae, and P. aeruginosa) complicates management of infections by requiring parenteral therapy with other antibiotics for organisms resistant to these oral agents, as well as increasing the burden of resistant organisms (31). Hence, the appropriate use of quinolones in LTCFs must be periodically assessed. F. Trimethoprim-Sulfamethoxazole This antibiotic is commonly prescribed in the elderly, for urinary tract infections, chronic bacterial prostatitis, lower respiratory tract infections, and bacterial diarrhea caused by susceptible pathogens. Data are limited on the pharmacokinetics of this drug in elderly persons (32). Oral drug absorption does not appear to be affected by age. Renal clearance of trimethoprim is decreased in older persons. The recommended doses for use in the elderly are comparable to those prescribed in younger persons: with renal impairment and a creatinine clearance of less than 30 mL/min but greater than 15 mL/min, the dosage is reduced by half. The drug should be avoided if the creatinine clearance is less than 15 mL/min. G. Miscellaneous Antibiotics Other antibiotics that could be prescribed in residents of LTCFs and deserve brief mention include vancomycin, the new FDA-approved antibiotics quinupristin
dalfopristin (Synercid®) and linezolid (Zyvox®), and metronidazole. Vancomycin is a glycopeptide antibiotic used primarily for gram-positive bacterial infections. It is highly active against staphylococci (including MRSA) and streptococci (including vancomycin-sensitive enterococci). In the elderly, studies have indicated that reduced clearance of vancomycin is a consequence of reduced systemic and renal clearance as well as enhanced tissue binding of the drug. Lower parenteral doses are recommended for the frail elderly, and the dose should be adjusted according to the serum peak and trough levels as well as the creatinine clearance (33). The side effect profile in the elderly is no different from that in the general population. Quinupristin-dalfopristin, which is a streptogramin, is indicated in adults, including the elderly, for the treatment of serious and life-threatening or bac-

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teremic infection with vancomycin-resistant enterococci (VRE) and complicated skin and skin structure infection with MSSA and Streptococcus pyogenes (34). The pharmacokinetics of this agent are similar to that in younger adults. Linezolid, an oxazolidinone, is active against infections caused by sensitive gram-positive bacteria as well as MRSA and VRE (35). This agent’s availability, both in parenteral and oral formulations, as well as its relatively safe profile, is particularly advantageous in management of infections caused by such gram-positive-resistant organisms commonly encountered in elderly LTCF residents (see Section III). The indications, doses, and toxicities of metronidazole are no different in the elderly. The drug is commonly prescribed in combination with agents active against aerobic gram-positive and gram-negative bacteria to treat mixed infections in the elderly, such as infected pressure ulcers, diabetic foot ulcers, intra-abdominal infections, or pyogenic brain abcesses (27). Oral metronidazole is the agent of choice for the treatment of C. difficile colitis. Administered orally, this agent is absorbed well and achieves excellent tissue levels. Gastrointestinal intolerance is a common side effect. H. Antituberculous Agents Because most tuberculosis cases in the elderly are caused by isoniazid-sensitive and rifampin-sensitive Mycobacterium tuberculosis, the primary drugs for the treatment of active tuberculosis disease in this age group are isoniazid and rifampin. Isoniazid also should be used for the treatment of latent tuberculosis infection when the appropriate indications are present (see Chapter 15). I. Antifungal Agents Similar to younger adults, the commonly prescribed systemic antifungal agents in the elderly include amphotericin B, fluconazole, and itraconazole. Because of the potential toxicity of amphotericin B to renal function in the elderly, this agent must be used with caution. Fluconazole, because of its relative safety and efficacy and excellent bioavailability when administered by parenteral and oral routes, is prescribed more often in aging individuals. Itraconazole, available by parenteral and oral formulations, is an acceptable alternative, when indicated (see chapter 25). J. Antiviral Agents The antiviral agents commonly prescribed in the elderly include amantadine, rimantadine, acyclovir, valacyclovir, and famciclovir. Amantadine and rimantadine are recommended for influenza A infection within 48 hours of illness onset in the ambulatory elderly to reduce the duration and severity of illness; in institutional-

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ized elderly, these drugs are recommended for prophylaxis during an influenza A outbreak within the institution (see Chapter 13). Both drugs are continued for a minimum of 2 weeks or until approximately 1 week after the end of the outbreak. The neurominidase inhibitors, zanamivir and oseltamivir, are available for use in influenza A and B infections; efficacy and safety in elderly patients have not been extensively studied. Acyclovir, valacyclovir, and famiciclovir are effective agents for the treatment of herpes simplex and herpes zoster infection. Pain from herpes zoster and chronic pain (postherpetic neuralgia) may be relatively diminished by administering these agents within the first 72 hours of the onset of illness (see Chapter 17).

REFERENCES 1. 2. 3. 4. 5.

6. 7.

8. 9. 10. 11. 12.

13.

Haley RW, Culver DH, White JW. The nationwide nosocomial infection rate: A new need for vital statistics. Am J Epidemiol 1985; 121:159. Yoshikawa TT. VRE, MRSA, PRP, and DRGNB in LTCF: Lessons to be learned from the alphabet. J Am Geriatr Soc 1998; 46:241–243. Katz PR, Beam TR Jr, Brand F, Boyce K. Antibiotic use in the nursing home physician practice patterns. Arch Intern Med 1990; 150:1465–1468. Warren JW, Palumbo FB, Fitterman L, Speedie SM. Incidence and characteristics of antibiotic use and aged nursing home patients. J Am Geriatr Soc 1991; 39:963–972. Lee YL, Thrupp LD, Friis RH. Nosocomial infections and antibiotic utilization in geriatric patients: A pilot prospective surveillance program in skilled nursing facilities. Gerontology 1992; 38:223–232. Zimmer JG, Bentley DW, Valenti WM, Watson NM. Systemic antibiotic use in nursing homes: A quality assessment. J Am Geriatr Soc 1986; 34:703–710. Pickering TD, Gurwitz JH, Zalenznik D, Noonan JP, Avorn J. The appropriateness of oral fluoroquinolone-prescribing in the long-term care setting. J Am Geriatr Soc 1994; 42:28–32. Miller SW, Warnock R, Marshall LL. Appropriateness of antibiotic prescribing for urinary tract infections in long-term care facilities. Consult Pharm 1991; 14:157–177. Hanlon JT, Schmader KE, Samsa GP. A method for assessing drug therapy appropriate. J Clin Epidemiol 1992; 45:1045–1051. Norman DC. Fever and aging. Infect Dis Clin Pract 1998; 7:387–390. Yoshikawa TT, Norman DC. Fever in the elderly. Infect Med 1998; 15:704–706. Loeb M, Bentley DW, Bradley S, Crossley K, Garibaldi R, Gantz N, McGeer A, Muder RR, Mylotte J, Nicolle LE, Nurse B, Paton S, Simor AE, Smith P, Strausbaugh LJ. Development of minimum criteria for the initiation of antibiotics in residents of long-term-care facilities: Results of a consensus conference. Infect Control Hosp Epidemiol 2001; 22:120–124. Nicolle LE, Bentley DW, Garibaldi R, Neuhaus EG, Smith PW, the SHEA LongTerm Care Committee. Antimicrobial use in long-term-care facilities. Infect Control Hosp Epidemiol 2000; 21:537–545.

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Rajagopalan et al. Crossley K, Henry K, Irvine P, Willenbring K. Antibiotic use in nursing homes: Prevalence, cost, and utilization review. Bull NY Acad Med 1987; 63:510–518. Gurwitz JH, Field TS, Avorn J, McCormack D, Jain Shailavi, Eckler M, Edmonson AC, Bates DW. Incidence and preventability of adverse drug events in nursing homes. Am J Med 2000; 109:87–94. Gurwitz JH, Sanchez-Cross MT, Eckler MA, Matulis J. The epidemiology of adverse and unexpected events in the long-term care setting. J Am Geriatr Soc 1994; 42:33– 38. Rho JP, Yoshikawa TT. The cost of inappropriate use of anti-infective agents in older patients. Drugs Aging 1995; 6:263–267. Mylotte JM. Antimicrobial prescribing in long-term care facilities: Prospective evaluation of potential antimicrobial use and cost indicators. Am J Infect Control 1999; 27:10–19. Myers BR, Wilkinson P. Clinical pharmacokinetics of antibacterial drugs in the elderly: Implications for selection and dosage. Clin Pharmacokinet 1989; 17:385–395. Kinirons MT, Crome P. Clinical pharmacokinetic considerations in the elderly: An update. Clin Pharmacokinet 1997; 33:302–312. Bennett W. Geriatric pharmacokinetics and the kidney. Am J Kidney Dis 1990; 26:283–288. Guay DRP. Quinolones. In: Yoshikawa TT, Norman DC, eds. Antimicrobial Therapy in the Elderly Patient. New York, Marcel Dekker, Inc., 1994:237–310. Ernest ME, Ernst EJ. Effectively treating common infection in residents of long-term care facilities. Pharmacotherapy 1999; 19:1026–1035. Bouza E, Munoz P. Monotherapy versus combination therapy for bacterial infections. Med Clin North Am 2000; 84:1357–1389. Zaske DE. Aminoglycides. In: Yoshikawa TT, Norman DC, eds. Antimicrobial Therapy in the Elderly Patient. New York, Marcel Dekker, Inc., 1994:183–235. Dew RB III, Susla GM. Once-daily aminoglycide treatment. Infect Dis Clin Pract 1996; 5:12–24. Rajagopalan S, Yoshikawa TT. Antimicrobial therapy in the elderly. Med Clin North Am 2001; 85:133–147. Marrie TJ. Community-acquired pneumonia in the elderly. Clin Infect Dis 2000; 31:1066–1078. Naughton BJ, Mylotte JM. Treatment guidelines for nursing-home acquired pneumonia based on community practice. J Am Geriatr Soc 2000; 48:82–88. Owens RC Jr, Ambrose PG. Clinical use of fluoroquinolones. Med Clin North Am 2000; 84:1447–1469. Strausbaugh LJ, Crossley KB, Nurse BA, Thrupp LD, the SHEA Long-Term Care Committee. Antimicrobial resistance in long-term-care facilities. Infect Control Hosp Epidemiol 1996; 17:129–140. Williams L, Bender BS. Trimethoprim-sulfamethoxazole. In: Yoshikawa TT, Norman DC, eds. Antimicrobial Therapy in the Elderly Patient. New York, Marcel Dekker, Inc., 1994:169–181. Yoshikawa TT. Antimicrobial therapy for the elderly patient. J Am Geriatr Soc 1990; 38:1353–1372.

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Nichols RL, Graham DR, Barriere SL, and the Synercid Skin and Skin Structure Infection Group. Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: Two randomized, multicenter studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. J Antimicrob Chemother 1999; 44:263–273. 35. Chien JW, Kucia ML, Salata RA. Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin Infect Dis 2000; 30:146–151.

12 Urinary Tract Infection Lindsay E. Nicolle Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada

I. INTRODUCTION The most common infection that occurs in elderly residents of long-term care facilities (LTCFs) is urinary tract infection (1). It is the most frequent source of bacteremia, and a common reason for transfer of residents to acute care facilities. Urinary infection is also one of the most common indications for antimicrobial therapy in these facilities, and much of the antimicrobial use for urinary infection in LTCFs is inappropriate (2). Thus, an understanding of urinary infection in residents of LTCFs is important for optimal resident care and to promote appropriate antimicrobial use in this setting. The term urinary tract infection simply means the presence of a microbial pathogen within the normally sterile urinary tract. However, it is generally used in the context of isolation of organisms in the urine at a quantitative level that excludes contamination (3). Urinary infection may be asymptomatic—also called asymptomatic bacteriuria—when microorganisms are present in the urinary tract but there are no symptoms or signs referable to urinary infection in the host (4). Individuals with asymptomatic infection usually have evidence of an inflammatory or immune host response in the urinary tract. The term “colonization” is sometimes used, rather than asymptomatic bacteriuria. However, this term does not have any clinical relevance and is not used in this chapter. An important group of individuals with urinary infection in LTCFs are those patients with bladder drainage who are using chronic indwelling catheters (5). The epidemiology of infection, including morbidity, differs for residents with longterm use of catheters compared with elderly individuals with urinary infection 173

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without long-term indwelling catheters. Thus, patients in LTCFs with long-term indwelling catheters are generally discussed separately. Observations herein should be considered relevant only for residents without indwelling catheters, unless stated otherwise.

II. EPIDEMIOLOGY AND CLINICAL RELEVANCE A. Prevalence and Incidence The prevalence of urinary infection in elderly residents of LTCFs is high (Table 1). Approximately 30% to 50% of women have positive urine cultures at any time. The prevalence in men is only slightly lower, at 20% to 40%. This remarkable prevalence has been consistently reported from different countries over many years (6–12). The incidence of both symptomatic and asymptomatic urinary infection is also high in these populations (Table 2). In prospective studies of nursing homeacquired infections, symptomatic urinary infection is reported as the first or second most frequent infection, with an incidence of 1.07 to 1.9/1,000 resident days (Table 2). The definitions used for symptomatic urinary infection, however, lack specificity and may overestimate urinary infection. Studies that have used more restrictive definitions report rates of symptomatic infection of 0.14/1,000 days (20), or 0.5/10,000 days for infection with fever (21). Similarly, symptomatic in-

Table 1 Prevalence of Urinary Infection in Long-Term Care Facility Populations Female Population (reference) Nursing home, USA (6) incontinent, mean age 85 yr Nursing home, Greece (7) mean age 78 yr Psychiatric long-term care, Denmark (8) mean age 78 yr Veteran’s, Canada (9) mean age 80 yr Nursing homes, USA (10) incontinent, mean age 88 yr Long-term care, Canada (11) mean age 83 yr Nursing home, USA (12) mean age 83 yr

Male

Number

% positive

Number

% positive

158

57

56

25

231

27

121

19

178

15

79

13

59

37

101

29

101

53

160

18–33

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Table 2 Incidence of Urinary Infection Reported in Long-Term Care Facility Populations Institution Men Veteran’s, Canada (9) Veteran’s, Tennessee (14) Veteran’s, Portland (17) Women Skilled nursing facility, Canada (11) Both/Not Stated Veteran’s (13) Nursing homes, San Diego (15) Nursing homes, Wisconsin (16) Nursing homes, Maryland (18) Skilled nursing facility, NY (19)

Asymptomatic

Symptomatic

1.23

1.37 1.17 1.07

3.52

1.41 1.9 1.26 1.6 1.2–1.3 2.4

Episodes/1000 patient days.

fection in women is reported to occur at a rate of 1.41/1,000 days with inclusive criteria for identification of urinary infection, but only 0.22/1,000 days with more restrictive criteria that require genitourinary symptoms (11), and in men, 1.37/1,000 days with inclusive and only 0.38/1,000 days with more restrictive criteria. The frequency of asymptomatic bacteriuria has also been characterized through the “turnover” of bacteriuria with repeated prevalence surveys in the same population. One study (9) reported an initial prevalence of bacteriuria of 19% for men and 27% of women in a Greek home for the aged. At 1 year, 11% of men and 23% of women with initially negative urine cultures had developed positive cultures; 22% and 27% with initially positive urine cultures had become negative. Another study (12) reported an initial prevalence of bacteriuria of 25% in women, with 8% of residents with negative urine cultures becoming positive every 6 months, and 31% of residents with initial positive urine cultures becoming negative. A third study (22) reported an initial prevalence of bacteriuria of 15% in a group of elderly women residents in both community housing and long-term care. The monthly probability of transition from positive to negative cultures was 0.30, and 0.12 from negative to positive. In another study in elderly institutionalized men, 10% of all nonbacteriuric residents became bacteriuric in a 3-month period (9). Some residents have persistent bacteriuria, whereas others have acquisition of new organisms or clearing of bacteriuria. Thus, bacteriuria within a nursing home population is dynamic. Factors that contribute to the variation, including antimicrobial use, are not well studied.

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B. Risk Factors Urinary infection in residents of LTCFs is predictably associated with certain aspects of functional status. Residents with cognitive impairment, or who are incontinent of urine or bowel, are likely to have bacteriuria (23,24). In one study, 78% of men with persistent bacteriuria had dementia compared with 42% of those without bacteriuria, and 96% and 25%, respectively, were incontinent of urine (23). Impaired mobility and more prolonged duration of admission to the LTCF are also associated with bacteriuria in some studies (24,25). No association between specific medication use and urinary infection has been reported (26). Risk factors for symptomatic and asymptomatic infection appear to be similar (27). The most important determinant of bacteriuria in the long-term care population appears to be the presence of a neurogenic bladder. Chronic neurologic diseases, such as Alzheimer’s, Parkinson’s, or cerebrovascular disease, are often accompanied by a neurogenic bladder. These illnesses frequently lead to institutionalization and are associated with cognitive impairment and incontinence of bladder and bowel. A neurogenic bladder results in incomplete voiding and increased likelihood of ureteral reflux, promoting both acquisition and persistence of infection. Drainage devices used to manage incontinence may also increase the frequency of urinary infection. The use of an external condom catheter for men with incontinence is associated with at least twice the occurrence of urinary infection compared with men who are incontinent but who do not use external condom catheters (28). Previous indwelling catheter use may have initiated bacteriuria and prostatic infection. Once prostatic infection is established, it often cannot be eradicated and may be a source for bacteriuria causing relapsing symptomatic or asymptomatic infection (29). Physiologic aging changes also have been associated with urinary infection in well, community-living elderly populations and may contribute to urinary infection in the nursing home setting. Women with prior genitourinary surgery or who have cystoceles are more likely to have recurrent urinary infection (30). The use of topical vaginal estrogen decreases the occurrence of both symptomatic and asymptomatic infection (31), but the extent to which estrogen deficiency independently contributes to urinary infection in this population is not established. Prostatic hypertrophy is a uniform accompaniment of aging in men. This may lead to urethral obstruction and urinary retention requiring instrumentation, and promotes turbulent urethral urine flow, which facilitates ascension of organisms into the bladder (29). Thus, a variety of factors contribute to the high frequency of urinary infection in elderly residents of LTCFs. Different influences will, of course, have different importance depending on the individual resident. C. Microbiology The diversity of infecting organisms isolated is greater in the LTCF than from urinary infection in community populations (Table 3). The Enterobacteriaceae are

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Table 3 Distribution of Infecting Organisms Isolated in Surveys of Bacteriuria in Nursing Home Residents Number of isolates (%) reported in studies (references) indicated Organisms Escherichia coli Klebsiella spp Enterobacter spp Citrobacter spp Serratia spp Proteus mirabilis Providencia stuartii Morganella morganii Providencia spp Pseudomonas aeruginosa Other gram-negative Enterococcuss spp Coagulase-negative staphylococci Staphylococcus aureus Other gram-positive Candida spp

9*

11†

14*

19‡

13 (11) 7 (5.9) 2 (1.7) 3 (2.5)

30 (53)

67 (50) 20 (15) 5 (3.8) 1 (0.8)

36 (30) 5 (4.2) 3 (2.5) 14 (11.8) 23 (19)

14 (25)

38 (12) 26 (8.3) 3 (1.0) 12 (3.9) 20 (6.4) 57 (18)

60 (19) 34 (11)

5 (3.8)

2 (0.6) 34 (11) 2 (0.6) 2 (0.6) 3 (1.0)

6 (4.5) 6 (4.5) 1 (0.8)

6 (5.0) 2 (1.7) 3 (2.5) 2 (1.7)

11 (19) 1 (1.8) 1 (1.8)

22 (17)

* male † female ‡ 80% female

the most common infecting organisms for both symptomatic and asymptomatic infection. Escherichia coli is the most frequent bacteria isolated in women, with Proteus mirabilis usually second. For men, E. coli and P. mirabilis occur with equal frequency, or P. mirabilis is more common. Other Enterobacteriaceae isolated include Klebsiella pneumoniae and urease-producing organisms such as Providencia stuartii and Morganella morganii. Providencia stuartii has a unique predilection for the institutionalized population (32). Pseudomonas aeruginosa and gram-positive organisms including Enterococcus spp and coagulase-negative staphylococci, are also common. Group B streptococci and Staphylococcus aureus are less frequent but are identified in some patients in most series. Yeast infection, principally caused by Candida albicans, may occur but is uncommon. The determinants of candiduria in LTCF residents are not well described. Yeast infection may be more common in women with associated vulvovaginal candidiasis and in diabetic patients. The distribution of organisms isolated from symptomatic infection is similar to that for asymptomatic infection, although coagulase-negative staphylococci are uncommon in symptomatic infection.

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Polymicrobial infection is present in 10% to 25% of bacteriuric residents (9,11). Men with external condom catheters used for voiding management often have infection with more than one organism (33). Bacterial isolates from urinary infection in LTCF residents are also characterized by increased antimicrobial resistance (34,35). This is a result of the intense use of antimicrobials in nursing homes (2), as well as the transmission of organisms between residents in the institutional setting. D. Host Response Asymptomatic bacteriuria is not simply the presence of bacteria in the bladder. In fact, at least 50% of women with asymptomatic infection have bacteria localized to the kidneys (36,37). Pyuria is present in more than 90% of bacteriuric subjects (38,39). The level of pyuria does not correlate with the presence of symptomatic infection (40). Increased urinary cytokine levels and increased local urinary or systemic antibodies to the infecting organism are further evidence of a host response with asymptomatic infection (41,42). Symptomatic subjects uniformly have pyuria. There are also elevated levels of urinary cytokines and local urinary antibody (41,42). With resolution of the symptomatic episode, urinary antibodies may decrease, particularly with E. coli infection (42). In clinical presentations with systemic manifestations such as fever, an elevated C-reactive protein is usually present, and there is an increase in systemic antibody to the infecting organism (43). E. Clinical Impact The majority of urinary infections in residents of LTCFs are clinically asymptomatic (4). Persistent asymptomatic bacteriuria has not been associated with negative long-term outcomes, such as renal failure or hypertension. Despite the very high prevalence of urease-producing organisms, including P. mirabilis and P. stuartii, renal or bladder stones have not been identified as a significant clinical problem in LTCF residents without chronic indwelling catheters (9). Asymptomatic bacteriuria also does not affect survival (23,40). Where an association between decreased survival and bacteriuria in residents has been observed, bacteriuria is not an independent association of mortality (24). Episodes of febrile urinary infection have been reported with a frequency of 1 to 1.5/10,000 resident days, comprising about one tenth of episodes of fever of any cause in this population (21). The urinary tract is the most common source of bacteremia in LTCF residents (44,45), although this occurs primarily in residents with an indwelling urinary catheter (46). It is also a reason for transfer of LTCF residents for acute hospitalization (47), contributing 8% of transfers at one facil-

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ity (48). Despite this, urinary infection is infrequently identified as a direct cause of death in residents (1,20). Urinary infection is one of the most common indications for antimicrobial prescriptions in LTCFs. From 20% to 60% of systemic antimicrobial courses are given for treatment of urinary infection (2). This intensive use of antimicrobials contributes to the emergence and persistence of antimicrobial resistance in the long-term care setting. F. Chronic Indwelling Catheter From 5% to 10% of residents of LTCFs have voiding managed with a long-term indwelling urethral catheter (49,50). The daily incidence of new infection for individuals with a long-term indwelling catheter is similar to that reported with short-term catheters, about 3% to 7% per day (5). Thus, anyone with a long-term indwelling catheter in place for longer than 30 days will be bacteriuric, and at any time the prevalence of bacteriuria in individuals with chronic catheters approaches 100%. Residents with long-term catheters are infected with a complex bacterial flora with two to five organisms present at any time (51). Proteus mirabilis, Proteus spp, Morganella morganii and P. aeruginosa are the most common organisms isolated, although many other gram-negative and gram-positive organisms also occur. Biofilm formation occurs on the catheter, primarily on the interior surface (52). This material consists of bacteria, extracellular bacterial substance, Mg2
, Ca2
, and Tamm-Horsfall protein from urine. It may also contain struvite if infection with a urease-producing organism is present. Biofilm contributes to catheter encrustation and obstruction (53). Bacteria growing in the biofilm are in an environment where they are relatively protected from the effect of host defenses or antimicrobials. Residents of LTCFs with chronic indwelling catheters experience increased morbidity attributable to urinary infection compared with LTCFs residents with bacteriuria who do not have an indwelling catheter. Febrile urinary infection is 10 times more frequent in these individuals (21,54), and bacteremia, primarily from a urinary source, is 40 times more frequent (46). A chronic indwelling catheter may also cause episodes of gross hematuria resulting from catheter trauma (55), and local suppurative complications including paraurethral abscesses, urethritis, epididymo-orchitis, or prostatic abscesses. Residents with indwelling catheters have a higher mortality than LTCF residents without chronic indwelling catheters, but this is attributable to underlying patient factors rather than urinary infection (50). At autopsy, residents with a long-term indwelling catheter have a higher frequency of histologic evidence for renal inflammation consistent with pyelonephritis compared with bacteriuric residents without an indwelling catheter (56,57).

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III. CLINICAL MANIFESTATIONS Urinary infection is usually asymptomatic. However, symptomatic urinary infection is an important contributor to morbidity in LTCF residents. When symptomatic infection occurs, the clinical presentation may vary across a spectrum of minor lower tract irritative symptoms to severe systemic symptoms and sepsis requiring hospitalization. Potential clinical presentations of symptomatic infection are listed in Table 4. The presentation may be similar to that in younger populations. For acute lower tract infection, or acute cystitis, frequency, dysuria, urgency, the new onset or worsening of urinary incontinence, and suprapubic discomfort may occur. Acute pyelonephritis may present with costovertebral angle pain and tenderness with fever. The clinical diagnosis, however, is often not straightforward because of chronic symptoms that interfere with assessment, difficulties in communication because of deafness, cognitive impairment, or dysarthria, and blunted clinical manifestations associated with aging, such as a decreased or absent fever response (58). Sepsis, often with bacteremia, is more frequent with obstruction or trauma to the genitourinary tract. Epididymo-orchitis may occur in male residents. Hematuria is seldom caused by urinary infection, but gross hematuria will frequently lead to secondary sepsis in the presence of infected urine (55). Chronic genitourinary symptoms are common in this population. These include chronic incontinence, nocturia, and frequency. A high proportion of residents with chronic genitourinary symptoms have positive urine cultures, but Table 4 Presentations of Symptomatic Urinary Tract Infection in Residents of LongTerm Care Facilities Symptomatic Urinary Infection Acute cystitis (frequency, dysuria, suprapubic discomfort) Acute deterioration in continence Acute pyelonephritis (costovertebral angle pain/tenderness; often with fever) Fever with hematuria Fever with no localizing findings (10% due to urinary infection) Epididymo-orchitis Additional Presentations with Indwelling Catheters Fever with catheter obstruction Urethritis Paraurethral abscess Bladder spasms with bypassing of catheter by urine Not Symptomatic Urinary Infection Chronic genitourinary symptoms Cloudy or foul-smelling urine Clinical deterioration without fever or localizing genitourinary symptoms or signs

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chronic symptoms are not attributable to urinary infection and are not improved by antimicrobial treatment of urinary infection (59,60). Thus, chronic genitourinary symptoms are not a manifestation of symptomatic urinary infection. However, acute deterioration in symptoms, such as in continence status, may be consistent with acute infection. Urinary tract infection may also present as fever without localizing findings. Fever with no apparent source is a relatively common clinical manifestation of many different infections in elderly institutionalized populations. About 50% of these episodes occur in residents with positive urine cultures because of the very high prevalence of bacteriuria in these facilities. However, only 10% of episodes of fever without localizing findings appear to be of urinary origin (20). Unfortunately, criteria to differentiate urinary infection from other potential sources of fever if localizing findings are not present have not been identified. Clinical deterioration without fever or localizing genitourinary findings is also often attributed to urinary infection. However, in the absence of fever, urinary infection is unlikely to be the cause of a nonspecific decline in resident status (61). A. Long-Term Indwelling Catheters The most common presentation of symptomatic urinary infection in the resident with a long-term indwelling catheter is fever without localizing genitourinary findings (54). Symptoms or signs localized to the genitourinary tract may include costovertebral angle pain or tenderness, suprapubic tenderness, hematuria, or catheter obstruction. Bacteremia may be present (44–46). Lower tract symptoms such as suprapubic tenderness or bypassing of the catheter because of bladder spasms may also occur, but are less common. Local suppurative complications including epididymo-orchitis, prostatic abscess, paraurethral abscesses, or urethritis occur in men. Bladder or kidney stone formation is a potential long-term complication in residents with infection with urease-producing organisms such as P. mirabilis or P. stuartii.

IV. DIAGNOSTIC APPROACH A. Microbiologic Diagnosis A diagnosis of urinary infection requires an appropriately collected and transported urine specimen that is cultured quantitatively. For a diagnosis of asymptomatic bacteriuria, two consecutive urine cultures growing 105 or more colonyforming units/ml (cfu/ml) is necessary (3). Symptomatic infection is diagnosed with only one urine culture meeting this quantitative criteria. A lower quantitative count may be consistent with a microbiologic diagnosis of symptomatic infection in some clinical settings. Individuals receiving diuretics, who have renal failure,

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or who are infected with selected fastidious organisms may have quantitative counts lower than 105 cfu/ml. If complete obstruction is present and the infection is proximal to the obstruction, urine cultures may be negative. Urine culture will also usually be negative if antimicrobial therapy is initiated before obtaining the urine specimen. Lower quantitative counts may be consistent with infection with clinical presentations in some other populations, such as acute cystitis in young women, but lower quantitative criteria have not been validated for any presentations of urinary infection in the elderly. As 10% to 25% of bacteriuric men or women in LTCFs have more than one organism isolated (9,11), urine specimens with more than one uropathogen in appropriate quantitative counts should not be dismissed as contamination. Interpretation of quantitative urine bacteriology depends on a urine specimen collected to minimize contamination with urethral and periurethral flora. For men, a clean-catch specimen collected with voiding is usually adequate and unlikely to have substantial contamination. If a male resident cannot cooperate to provide a voided specimen, collection using a freshly applied clean condom and leg bag may provide a suitable specimen (33,62). For women, a clean-catch technique also usually provides an adequate specimen (63). A clean-catch technique also has been shown to be feasible in incontinent female nursing home residents, provided the resident is cooperative and staff are properly trained (64). However, many women may not be able to cooperate with voiding for specimen collection (11). The use of pedibags, bedpans, or diapers in collecting urine specimens from women is discouraged, as these methods are subject to substantial contamination with periurethral organisms and have not been validated. When a resident is unable to cooperate and a urine culture is indicated to assist with clinical management, in and out urethral catheterization for specimen collection should be used. Any quantitative count of a potential uropathogen is diagnostic of infection in a urine specimen collected by catheterization. This procedure, however, may introduce infection in as many as 5% of catheterizations and should only be used if there is a compelling clinical indication. B. Urinalysis More than 90% of elderly residents of LTCFs with bacteriuria will have pyuria, regardless of whether infection is symptomatic or asymptomatic (38,39). In addition, 30% of residents without bacteriuria also have pyuria, presumably caused by periurethral contamination or other inflammatory conditions within the genitourinary tract. Thus, pyuria is not specific for a diagnosis of bacteriuria or for differentiating symptomatic from asymptomatic infection. However a urinalysis for determination of pyuria is useful if it is negative, as absence of pyuria has a high negative predictive value to exclude bacteriuria. The leukocyte esterase dipstick test has been evaluated for identification of pyuria in elderly institu-

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tionalized populations (6,22,39). It has a positive predictive value varying from 18% to 75% and a negative predictive value of 75% to 100% for identifying infection in this setting. Thus, it may be used as a rapid screening test to exclude urinary infection. C. Clinical Diagnosis When a resident presents with a new onset of irritative lower tract symptoms or with classic clinical findings of acute pyelonephritis, a diagnosis of symptomatic urinary infection may be straightforward. However, a diagnosis of symptomatic urinary infection is frequently problematic because of difficulties in communication and the presence of chronic symptoms associated with comorbid disease. The fever response is less marked or may be absent (58). Acute change in chronic symptoms, such as acute deterioration in continence status or increased frequency, may support a clinical diagnosis of symptomatic urinary infection. The resident with clinical deterioration without localizing genitourinary findings may present a diagnostic problem. Because a high proportion of these individuals have a positive urine culture, there is a tendency to attribute any change in clinical status for which no other explanation is apparent to urinary infection. However, urinary infection is not usually the cause for this presentation. One study reported urinary infection caused clinical deterioration without localizing findings in only 11% of such patients, and all those with urinary infection also had fever (61). In another study, fever without localizing findings was caused by urinary infection in only 10% of episodes (21). There were, however, no clinical or laboratory parameters to differentiate the 90% of episodes not linked to a urinary source from the 10% attributable to urinary infection. Thus, with a clinical presentation of fever without localizing findings in residents with a positive urine culture, some skepticism should be maintained with respect to a diagnosis of symptomatic urinary infection. Practitioners must recognize the uncertainty in attributing this clinical presentation to urinary infection. A negative urine specimen is useful to exclude urinary infection, but a positive urinary culture does not confirm symptomatic urinary infection. Careful clinical evaluation to identify localizing findings to support or exclude a genitourinary source should always be undertaken. The presence of “foul-smelling” or cloudy urine is also sometimes identified as symptomatic urinary infection and interpreted as an indication for antimicrobial therapy. Cloudy urine may be caused by crystals as well as pyuria, and even if pyuria is the cause, by itself it is not sufficient to diagnose symptomatic infection, nor is it an indication for antimicrobial therapy. An unpleasant urine odor may certainly be associated with urinary infection and is likely caused by polyamine production by infecting bacteria (65). However, not all residents with this problem have urinary infection and not all residents with urinary infection

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have an unpleasant odor. This “symptom” is more appropriately addressed through improved continence management rather than antimicrobial treatment. D. Long-Term Indwelling Catheters For microbiologic diagnosis of urinary infection in the resident with a chronic indwelling catheter, a specimen must be collected aseptically from the catheter port or by aspiration through the catheter tubing. Catheters that have been in situ for several days will have biofilm formation, primarily on the inner surface of the catheter. A urine specimen obtained from the catheter or tubing provides samples of the bacteriology of this biofilm rather than bladder urine. The microbiologic findings in a specimen obtained from the catheter differ quantitatively and qualitatively when compared with bladder urine (66,67). A higher number of bacteria and higher quantitative counts of organisms in the urine are isolated from a biofilm-laden catheter. Thus, where a urine specimen for culture is obtained to identify infecting organisms and susceptibilities, the indwelling catheter should be replaced, and a urine specimen obtained from the newly inserted catheter before antimicrobial therapy begins. The most common clinical presentation of symptomatic urinary infection in the catheterized patient is fever without localizing findings. At least 30% to 50% of such episodes in residents with an indwelling catheter have a urinary source (21). Thus, a diagnosis of symptomatic urinary infection with this clinical presentation is appropriate in the catheterized resident. Localizing findings, including hematuria, an obstructed catheter, suprapubic tenderness, or costovertebral angle pain or tenderness should be sought, as these increase the probability of a urinary source.

V. THERAPEUTIC INTERVENTIONS A. Asymptomatic Bacteriuria Asymptomatic bacteriuria in residents of LTCFs should not be treated. Prospective, randomized, comparative trials have repeatedly shown no decrease in morbidity or mortality with antimicrobial treatment of asymptomatic bacteriuria (9,11,24,68). Specifically, there is no decrease in acute episodes of symptomatic urinary infection, no change in chronic genitourinary symptoms, and no decreased mortality with treatment of asymptomatic bacteriuria (Table 5). Some studies have, in fact, reported a trend towards increased mortality with intensive antimicrobial therapy to attempt to maintain sterile urine (9,11). Treatment of asymptomatic bacteriuria does result in an increased incidence of new infection in treated residents, increased adverse effects from antimicrobial therapy, increased cost, and increased reinfection with more resistant organisms. Thus, studies are

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Table 5 Randomized Clinical Trials of Therapy and No Therapy for Management of Asymptomatic Bacteriuria in Long-Term Care Facility Residents Population

Number

Follow-up

Men (9)

36

2 years

Women (11)

50

12 months

358 191

8.5 years 3 days

35

mean 29.2 weeks

Women (23) Men and women (68) Long-term catheter (82)

Outcomes of therapy and no therapy • Similar for symptomatic episodes • Similar for mortality • ↑ infection, ↑ adverse effects, ↑ resistance with antimicrobial therapy • Similar symptomatic episodes and mortality • No difference in mortality • Treatment had no effect on chronic incontinence • No difference: bacteriuria, fever, catheter obstruction • ↑ Resistant bacteria with cephalexin

consistent in reporting no benefit with treatment of asymptomatic bacteriuria, and several harmful outcomes. It follows that routine screening of asymptomatic residents of LTCFs for the presence of asymptomatic bacteriuria is not indicated. B. Antimicrobial Treatment Antimicrobial therapy is certainly indicated for the treatment of symptomatic infection. Many different antimicrobials are effective for treatment of urinary infection (Table 6). Selection of a specific agent for treatment of an episode is directed by the known or presumed susceptibilities of the infecting organism, patient tolerance, evidence of prior efficacy of the antimicrobial in the management of urinary infection, and facility formulary. Antimicrobial selection is not altered on the basis of age alone (69). In every case, a urine specimen for culture should be obtained before instituting antimicrobial therapy. If possible, empirical treatment should be avoided. For individuals with mild lower tract symptoms or only lowgrade fever, institution of antimicrobial therapy should be delayed pending results of the urine culture. When the resident’s clinical status is severe enough to warrant empiric therapy, such as a resident with acute confusion, high fever, or hemodynamic instability, empirical antimicrobial therapy is indicated. The empirical regimen should be reassessed once the urine culture result is available, usually at 48 to 72 hours after start of treatment, and the initial clinical course and response to antimicrobial therapy can be reviewed.

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Table 6 Antimicrobials for Treatment of Urinary Tract Infection in Long-Term Care Facility Residents Regimen Oral Penicillins Ampicillin Amoxicillin Amoxicillin/clavulanic acid Piperacillin Piperacillin/tazobactam Cephalosporins Cephalexin Cefazolin Cefuroxime (axetil) Cefixime Cefotaxime Ceftriaxone Ceftazidime Aminoglycosides Gentamicin Tobramycin Amikacin Fluoroquinolones Norfloxacin Ciprofloxacin Ofloxacin Levofloxacin Gatifloxacin Moxifloxacin Other Trimethoprim Trimethoprim/sulfamethoxazole Nitrofurantoin Aztreonam Imipenem/cilastatin Meropenem Vancomycin*

Parenteral 1–2q 6h

500 mg tid 500 mg tid 3g q 4h 3.375g q 6h 500 mg qid 125–250 mg bid 400 mg od

1.0g q 8h 750 mg q 8h 1.0g q 8–12h 1.0g q 24h 1.0g q 8h 1–1.5 mg/kg q 8h or 3–4 mg/kg q 24h 1–1.5 mg/kg q 8h or 3–4 mg/kg q 24h 3–5 mg/kg q 8h or 15 mg/kg q 24h

400 mg bid 250–750 mg bid 200–400 mg bid 250–500 mg od 400 mg od 400 mg od

400 mg q 12h 500 mg od

100 mg bid 160/800 mg bid 100 mg bid 1.0g q 8h 500 mg q 6h 500 mg q 8h 1.0g q 12h

* Gram positive infections only. Abbreviations: OD, once daily; bid, twice daily; tid, three times daily; qid, four times daily.

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Few studies address the question of the optimal antimicrobial regimen for treatment of symptomatic urinary infection in residents of LTCFs. Thus, the relative efficacy of different antimicrobials and optimal duration of therapy are not known. For oral therapy, trimethoprim/sulfamethoxazole or trimethoprim alone may be preferred as initial therapy (2). If resistant organisms are known or thought to be causing infection, a quinolone antimicrobial may be appropriate, and for gram-positive infections, amoxicillin is usually preferred. Quinolone antimicrobials should be reserved for therapy when other oral options are not available, to limit emergence of resistance to this class of agents. Nitrofurantoin is useful for episodes of lower tract infection. It also has limited impact on the normal host flora and, on occasion, may be effective therapy for vancomycin-resistant enterococci. However, it is not effective for P. mirabilis infection, is not indicated for upper tract infection, and is contraindicated in patients with renal failure. When the resident’s clinical status or infection with antimicrobial-resistant organisms warrants parenteral therapy, an aminoglycoside antimicrobial such as gentamicin may be considered (2). A relatively safe and convenient dosage regimen for aminogylcosides is once-daily administration (70), which may be feasible in a long-term care setting. Gentamicin or tobramycin may be given intramuscularly or intravenously in a dose of 3 to 4 mg/kg/day every 24 to 48 hours depending on renal function of the resident (70). Aminoglycosides may be given either intravenously or intramuscularly. Aminoglycoside use avoids the extendedspectrum cephalosporins or quinolones, limiting antimicrobial pressure for emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae or quinolone-resistant organisms, both of which have been identified as a concern in LTCF populations. When empirical therapy with an aminoglycoside is initiated, the clinical course and infecting organism should be reassessed after 48 to 72 hours to ensure that the aminoglycoside remains optimal therapy and that parenteral therapy is still required. In many cases, the aminoglycoside may be changed to an alternative parenteral or oral drug at this time. If a more prolonged course of aminoglycoside therapy is indicated, then aminoglycoside levels and renal function should be monitored at least twice weekly. However, in LTCFs, such regular assessments may not be feasible and alternative agents such as quinolones, extended-spectrum cephalosporin, or a carbapenen should be considered. Aminoglycosides are not an appropriate empiric choice for individuals with renal failure and in this setting, a parenteral quinolone antimicrobial or an extended-spectrum cephalosporin would be preferred. C. Duration of Treatment Few studies are available to define the optimal duration of treatment. For minor lower tract symptoms, a 7-day of course of therapy is adequate. Shorter courses of 3 to 5 days are less effective than in younger women with acute cystitis and are

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not recommended for this population. More severe clinical presentations with evidence of systemic illness should be treated for 10 to 14 days. In a few selected clinical indications, longer courses of antimicrobial therapy may be necessary. Men with symptomatic relapsing infection from a prostatic source may require 6 or 12 weeks of treatment (71,72). Residents with recurrent episodes of invasive infection and an abnormality of the genitourinary tract that promotes infection and cannot be corrected, including infection stones that cannot be removed, may benefit from long-term suppressive therapy (73). This is undertaken in only highly selected patients, and specific therapy chosen on a case by case basis. Long-term antimicrobial therapy should always be embarked on with care, as it is likely to promote emergence of resistant organisms. D. Chronic Indwelling Catheters The principles of antimicrobial selection in residents with chronic indwelling catheters are similar to those for residents without indwelling catheters. The catheter should be changed before initiating antimicrobial therapy, so the urine specimen obtained reflects the microbiology of bladder urine rather than biofilm on the catheter. Replacement of the catheter before instituting antimicrobial therapy may also lead to improved clinical outcomes, such as more rapid defervescence of fever and a decreased occurrence of symptomatic relapse (74). The optimal duration of antimicrobial therapy for treatment of a symptomatic episode in a patient with a chronic indwelling catheter is not known. However, the continuing presence of the catheter will result in recurrent urinary infection, and antimicrobial therapy promotes reinfection with organisms of increasing resistance. Thus, the duration of antimicrobial therapy should be as short as possible. In residents with a prompt clinical response and rapid defervescence of fever, a 7-day course of therapy should be sufficient.

VI. INFECTION CONTROL MEASURES A. General The goals of infection control measures in the LTCF are to prevent acquisition of infection by residents and prevent transmission of organisms between residents. The most important interventions are appropriate hand washing and glove use by staff members, use of aseptic or clean technique in patient care, and effective cleaning of equipment. A particular concern related to urinary infection in the LTCF is the cleaning and drying of leg bags for individuals using a condom or indwelling catheter (75). Surveillance for infection identifies the presence and extent of specific problems and by itself may contribute to decreasing infection rates as staff are made aware of the burden of morbidity. Because of the high prevalence and lack

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of evidence of harm of asymptomatic bacteriuria in this population, routine urine collection for screening cultures is not appropriate. Surveillance should be undertaken for symptomatic urinary infection, including bacteremia from urinary sources (75). Any surveillance strategy must have a capacity for early identification of potential outbreaks. Antimicrobial use for urinary infection should also be monitored, together with a means of assessing the appropriateness of such use. B. Long-Term Indwelling Catheters The urine from individuals with long-term indwelling catheters is a reservoir for resistant organisms within the long-term care setting. Thus, care must be taken to limit transmission of organisms, through equipment or the hands of staff, between patients with chronic catheters. Urine-measuring devices should not be shared among patients, appropriate glove and hand-washing practices by staff members in catheter care should be maintained, and policies governing catheter care in LTCF patients should be developed and updated regularly. These policies should also specify when long-term indwelling catheters should be used and how catheter use should be monitored to assist in limiting use. Surveillance of long-term indwelling catheter use should include the prevalence of catheter use, reasons for catheter use, and reasons why the catheter cannot be removed in a given individual. As all residents with chronic indwelling catheters are bacteriuric, there is no indication for routine screening for the presence of bacteriuria. However, surveillance for symptomatic urinary infection should be performed, including surveillance for episodes of catheter obstruction or trauma.

VII.

PREVENTION

A. General Measures The major factors promoting urinary tract infection in elderly residents of LTCFs are associated comorbid diseases leading to a neurogenic bladder. As these are the same comorbidities that lead to admission to the LTCF and, in most cases cannot be altered, it is not clear whether any current interventions can prevent bacteriuria. As a general approach to care, optimizing nutrition, mobility, and medical management of comorbid illnesses is desirable, but the impact of these on the occurrence of urinary infection is unknown. In fact, one clinical study reported that improving nutrition of LTCF residents did not decrease the occurrence of urinary infection (76). B. Specific Measures Several specific interventions may decrease the occurrence of urinary infection. The use of condom catheters is associated with an increased frequency of infec-

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tion, so limiting the use of these devices should decrease the occurrence of bacteriuria. Whether this would also decrease the occurrence of symptomatic infection is unknown. In many cases, however, patient care requires the use of these devices, and it is unrealistic to think use can be entirely avoided. For individuals with voiding managed with intermittent catheterization, the frequency of infection is similar using a clean or sterile catheterization technique (77). Hence, clean, intermittent catheterization is appropriate and less costly. Increased intake of cranberry juice has been suggested as an approach to decrease infection. However, increased cranberry juice did not decrease the prevalence of bacteriuria or symptomatic infection in a placebo-controlled trial (78). Topical vaginal estrogen therapy decreased the occurrence of both symptomatic and asymptomatic infection in a group of elderly, institutionalized women with a very high frequency of symptomatic infection (79) and may be an approach for some women. Finally, trauma to the mucosa in an infected genitourinary tract is associated with a high risk of bacteremia and sepsis. Prophylactic antimicrobial therapy should be given before any invasive genitourinary procedure is undertaken in a bacteriuric resident, as this is effective in preventing these severe complications (80). C. Long-Term Indwelling Catheters The most effective way to avoid urinary infection associated with a long-term catheter is, of course, not to use the catheter or to limit the duration of use to as short a time as clinically necessary. Otherwise, bacteriuria cannot currently be prevented in a patient with a long-term indwelling catheter. Several specific interventions to decrease the frequency of catheter-associated infection have been evaluated, but none have been shown to be effective. For instance, routine daily bladder irrigation with saline does not decrease the incidence of infection (81), antimicrobial treatment of asymptomatic bacteriuria does not decrease the frequency of asymptomatic or symptomatic infection (82), and different catheter materials, such as latex or silicone, do not alter the rate of infection. Silicone catheters have been reported to have fewer episodes of obstruction and may be useful in patients with a high rate of obstruction. However, they have not been shown to decrease the occurrence of symptomatic infection and, as they are more costly, are recommended only for selected patients. Other interventions, such as daily periurethral cleaning with soap and water or with a disinfectant, or placing disinfectant in the drainage bag, do not decrease the frequency of bacteriuria in patients with shortterm indwelling catheters and would also be assumed to be ineffective for longterm catheters. Because the frequency of asymptomatic bacteriuria cannot be decreased, the focus of prevention must be to minimize the occurrence of symptomatic episodes. Appropriate catheter care to limit trauma, avoiding contamination with incontinent stool (e.g., securing the catheter to the upper thigh of the resident), and

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prompt identification and replacement of an obstructed catheter will prevent some episodes of symptomatic infection. In addition, the use of prophylactic antimicrobials before an invasive genitourinary procedure will prevent postprocedure sepsis and bacteremia (80). Prophylactic antimicrobials are not indicated with catheter change, as the risk of infectious complications with this intervention is not sufficient to warrant this intervention (83,84). The problem of urinary infection in the individual with a long-term indwelling catheter is a technical issue related to ensuring adequate urinary drainage, and catheter materials to prevent bacterial growth. Further technological developments, then, are necessary to make a substantial impact on the frequency of urinary infection in residents with long-term indwelling catheters. Current studies of different drainage devices, such as intraurethral catheters, or catheter materials to prevent bacterial growth, may result in improvements in the future.

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