Infections in Frail and Vulnerable Elderly Patients STEPHENR. JONES, M.D. Portland, Oregon
Frail and vulnerable elderly patients, recognized primarily by the presence of such disabilities as immobility, incontinence, and dementia, are at particularly high risk for the development of infectious diseases, which are the leading cause of hospitalization in this population. The infectious diseases most often observed in the debilitated elderly are pneumonias, urinary tract infectidns, skin infections, and gastroenteritis, with fever a common, manifestation. Some of the factors identified as contributing to their increased susceptibility include diminishing physiologic functioning; compromised host-defense mechanisms; increased incidence of mechanical risk factors, such as pressure ulcers, indwelling or condom catheters, feeding tubes, and soft tissue injuries; and comorbidities such as soft tissue or pulmonary edema. In addition to the common infecting pathogens found in the general population, these unique compromising factors increase the risk of elderly patients for aerobic gram-negative bacillary infection. Further increasing the therapeutic dilemma are ethical considerations involved in prolonging treatment that might be considered medical intervention beyond what is routine and necessary. Although the decision to treat must be made on an individual basis, studies have not always shown treatment to provide benefits in terms of quality of life. Once it is decided to treat, however, appropriate therapy ,is crucial. One of the most important considerations is renal function, which impacts on effectiveness, toxicity, and cost of therapy and is likely to be diminished in elderly patients. A non-nephrotoxic agent, such as aztreonam, may be a more appropriate therapeutic choice than an aminoglycoside antibiotic in this patient population.
lderly patients are at risk for infectious diseases E for a variety of reasons, including their frequently debilitated condition and the presence of serious underlying disease. Among the elderly, certain subgroups are particularly vulnerable to infection, and the pathophysiology and microbiology of their infections deserve special consideration. In addition, certain ethical questions must be explored in evaluating the clinical aspects and principles of management of the most common infections encountered in this frail and vulnerable population. RECOGNITION OF THE FRAIL AND VULNERABLE ELDERLY The three primary disabilities that define frail and vulnerable eiderly patients are immobility, incor$inence, and dementia; any of these can influence the patient’s placement in nursing homes and other highcare environments. The frail elderly have lower physiologic reserves for coping with intercurrent illness. They may, for example, be vulnerable to influenza A in many seasons, and they are more likely to die from it because they lack the normal homeostatic mechanisms that help a young, vigorous person survive. With influenza, the elderly are more likely to have pneumonia; to become delirious and fall, with resultant hip fractures; or to stay in bed and lose cardiovascular function and tone or develop pressure sores. Infectious diseases are the leading cause of hospital admissions among the frail elderly; they are responsible for hospitalization more often than cardiovascular, gastrointestinal, orthopedic, or any other problems. A study of transfers from the chronic-care facility to the acute-care hospital within one year at Francis Scott Key Hospital of the Johns Hopkins University revealed that 30 percent of the transfers were attributable to infectious disease problems [l]. In another study, Irvine and associates [Z] of the University of Minnesota reported that during a one-year period, 128 patients from nursing homes and 320 fro? &be geriatric clinic were hospitalized. As in the Johns Hopkins study, the leading cause of hospitalization of patients from the nursing homes was infectious diseases, which accounted for approximately 25 percent, whereas only 12 percent of hospitalizations from the geriatric clinic were due to infectious diseases. In both studies, pneumonia, urinary tract infections (UTIs), skin infections, and gastroenteritis were the principal infectious causes, with fever a common manifestation. FACTORS INFLUENCING THE VULNERABILITY OF THE ELDERLY Pathophysiologic Features of Infection
From the Good Samaritan Hospital, Oregon Health Sciences Unlverslty, Portland, Oregon. Requests for reprints should be addressed to Stephen R. Jones, M.D., Depatiment of Medicine, Oregon Health Sciences University, and Department of Medicine, Good Samaritan Hospital and Medlcal Center, 1015 NW 22nd Avenue, Portland, Oregon 97210.
3c-30s
March 23, 1990
The American Journal of Medicine
Many geriatric textbooks discuss accepted trends for measuring diminishing physiologic functions in the elderly, including cardiac index, glomerular filtration rate, vital capacity, and more. Other factors, however, also contribute to the susceptibility of the el-
Volume 88 (suppl 3C)
SYMPOSIUM
derly to infection. The host-defense mechanisms of this group, for example, may be markedly compromised. Host-defense mechanisms can be divided into three categories: those that operate at body surfaces, extracellular fluid factors, and cellular factors. Bodysurface factors include skin, mucous membranes, cough reflex, and the normal motility of the gastrointestinal and genitourinary tracts, as well as the more sophisticated host-defense mechanisms such as complement, T lymphocytes, immunoglobulins, and phagocytic cells. Despite extensive investigation, no consistent defects have been identified that appear to correlate clinically with the common infectious diseases of the elderly [3]. It appears that mechanical risk factors, rather than sophisticated host-defense defects, are responsible for impairment of body-surface functions. These factors include pressure ulcers, indwelling catheters, condom catheters, feeding tubes, and soft tissue injuries that result from handling of immobile patients by attendants. Important comorbidities common in the elderly also predispose them to infection. Soft tissue edema from lymphatic or venous stasis, heart disease, or low albumin, for example, may lead to cellulitis, and pulmonary edema is an important risk factor for development of pneumonia. Microbiologic Features of Infections
The usual site-pathogen rules for the general population remain valid for the frail elderly: Stu~hyZococcus is still the most common cause of skin infection; the pneumococcus, the most common cause of pneumonia; and Escherichia coli the most common pathogen involved in UTIs. The mucosal and skin-surface alterations discussed, as well as the source of the infectious pathogens, increase the risk for aerobic gramnegative bacillary infections in the frail elderly, who also are more likely to acquire gram-negative bacillary pneumonia, skin infections, and UTIs caused by antibiotic-resistant bacteria. PRESENTATION OF INFECTION The tendency for the manifestation of infection in the elderly to be subtle and nonspecific has been recognized for some time: In 1897, Osler [4] stated that: in the old and debilitated, a knowledge that the onset of pneumonia is insidious and that the symptoms are ill defined and latent should place the practitioner on his guard and make him very careful in the examination of the lungs in doubtful cases. In the study by Irvine and associates [Z], twice as many patients from the nursing homes as from the clinic had admitting complaints that were nonspecific for their primary diagnosis. In another study of infective endocarditis in three different age groups (younger than age 40, 40 to 60 years of age, and older than 60 years), it was revealed that the initial evaluation by admitting physicians mentioned endocarditis as a diagnostic possibility in 76 percent of those under age 40 but in only 32 percent of those older than age 60 151. Diagnosis of endocarditis, as well as other important infectious diseases, becomes more difficult as patients get older. ETHICAL CONSIDERATIONS Professionals in hospitals may inappropriately apply high technology to stop the perhaps appropriate
ON AZTREONAM / JONES
and inevitable demise of the frail elderly. According to Osler [6]: Pneumonia may well be called the friend of the aged. Taken off by an acute, short, often painless illness, the old escape those cold gradations of decay that make the last state of all so distressing. More distressing than fatal pneumonia to the elderly and their families is the anticipation of sustaining not a cold, slow death, but an intense slow death in a critical-care setting. Ethical dilemmas are unavoidable in selecting treatment for elderly patients. Antibiotics, for example, must be considered among the life-sustaining treatments, and there is legal precedent that such therapy can be viewed as medical intervention beyond what is routine and necessary. In 1983, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical Research 171 stated that: the Commission has found no particular treatments, including such ordinary hospital interventions as parenteral nutrition, hydration, or antibiotics, to be universally warranted. Nevertheless, the decision to forgo particular life-sustaining treatments is not a ground to withdraw all care, especially when care is needed to ensure patients’ comfort, dignity, and self-determination. Comfort, dignity, and self-determination are primary; antibiotics and other life-sustaining measures are optional. It may therefore be permissible and appropriate to withhold such treatment when such a course of action is decided on by directive of the patient, his family, and/or the clinician. In fact, studies have shown that this has been a standard of practice [8,9]. Clearly, an analytic framework is crucial for making decisions in the face of such an ethical dilemma. Cassel [lo] has suggested a series of steps that may be useful in reaching the annronriate decision: 1. Collect and be familiar v&hall data pertaining to the clinical problem. 2. Examine the motives of all of those who will be involved in making the decision-the family or person who has legal responsibility for the patient, as well as those involved in patient care. 3. Consider ethical principles. 4. Rank the principles. Examine the consequences of making the decision. 8: Make the decision. Most physicians have, at best, only rudimentary skills and knowledge for considering ethical principles. Among many sources, a 1987 publication from the Hastings Center 1111 provides guidelines on the termination of life-sustaining therapy that are quite useful; it contains a section on the use of antibiotics and other life-sustaining drugs that is particularly appropriate for these considerations. An investigation of the use of antibiotics in several long-term care facilities in Portland, Oregon, evaluated the majority (51 percent) of antibiotic prescriptions as inappropriate; 49 percent were considered appropriate 1121. Similar to most studies, the most common use of antibiotic therapy in this study cohort was for infections of the urinary tract (more than half of the 120 infections treated with antibiotics), respiratory tract, and skin. Trimethoprim was the drug most
March 23, 1990
The American Journal of Medicine
Volume 88 (suppl 3C)
3c-31s
SYMPOSIUM
ON AZTREONAM / JONES
frequently considered to have been used correctly. This study was conducted in 1986, and there have been advances in antimicrobial treatment since that time that may allow more appropriate treatment. SPECIFIC INFECTIONS THAT AFFECT THE ELDERLY UTIs, pneumonias, and skin and soft tissue infection most commonly affect the elderly. Urinary Tract infections
UTIs in the frail elderly can be categorized as follows: asymptomatic infections, either with or without a catheter, and symptomatic infections. In asymptomatic patients who have bacteriuria, treatment is generally not helpful. Although bacteriuric frail elderly patients die earlier than do such patients who are nonbacteriuric, a series of blinded, randomized controlled studies of bacteriuric frail elderly in nursing homes has not shown treatment to decrease morbidity or mortality [13-151. Another study has evaluated elderly persons who are less frail to determine whether eradicating the bacteriuria would make them more mobile, more continent, and less demented [16,17]. Unfortunately, the answer was still no. Asymptomatic bacteriuria in the elderly is not a public health menace. Only symptomatic infection requires investigative and therapeutic management.
mon isolates from these ulcers are among the Enterobacteriaceae, most frequently Proteus spp., although Staphylococcus aureus is also common. Importantly, Bacteroides frugilis is the most common isolate from the bloodstream, although Proteus is the most common aerobic isolate found in the bloodstream [20]. TREATMENT CONSIDERATIONS IN ELDERLY PATIENTS Clearly, gram-negative aerobic bacteria are an important cause of the most common infections encountered in elderly patients, and if these infections are to be treated, appropriate antimicrobial therapy must be carefully chosen. Currently, a variety of highly efficacious parenteral antimicrobial agents are available for treating aerobic gram-negative bacilli. These include aminoglycosides, third-generation cephalosporins, imipenem/cilastatin, and aztreonam, among others. When choosing an antibiotic regimen for this population, one of the most important factors to consider is renal function, which in turn dictates effectiveness, toxicity, and cost of treatment. Renal Function in the Elderly
Renal function persistently declines with age [21]. Although deterioration of renal function is likely to be more rapid in association with such disease-related conditions as diabetes mellitus, hypertension, and athLower Respiratory Tract infections erosclerosis, there is no doubt that it is age-related as Important factors are associated with pneumonia in well. the frail elderly. First, frail elderly patients are more A number of principles apply to the measurement of prone to aspiration and less likely to clear bacteria renal function in the elderly: (1) Serum creatinine once the lower respiratory tract is invaded than less alone is a poor measurement of renal function because frail persons. This may be attributed to a commonly of the progressively diminished muscle mass with age. poor cough reflex. The prevalence of aerobic gram- (2) Formal measurement of glomerular filtration is negative rods in the oropharynx is an important ante- tedious as well as retrospective, and other measurecedent to the development of lower respiratory tract ments are impractical. Timed creatinine clearance, for infection in the frail elderly. The prevalence of aerobic example, is progressively invalidated as the glomerugram-negative colonization of the oropharynx has lar filtration rate decreases, increasing proportionbeen compared in healthy and ill subjects and reveals ately the tubal excretion of creatinine [22]. (3) A simthat the incidence of gram-negative-rod colonization is ple estimation of the glomerular filtration rate using only 1 percent in healthy people, whereas between 24 the Cockcroft-Gault formula (140 minus age, divided and 50 percent of patients in intensive care units har- by serum creatinine) can indicate those patients with bor gram-negative rods in high numbers. In compariimportantly diminished renal function [23]. The result son, in an elderly nursing home population, an overall can then be adjusted for body weight of the patient by prevalence of 3’7 percent has been documented, with multiplying by the patient’s weight, divided by ‘72 kg. an incidence of 50 percent among the bedridden 1181. It is not necessary to adjust for gender in frail elderly Aerobic gram-negative rods are commonly present in patients because of the progressive decrease in muscle the oropharynx of the frail elderly, and if aspiration mass in elderly men [24]. occurs, these bacteria are found in high numbers. The frail elderly are particularly prone, therefore, to aero- Impact of Renal Function on Choice of Therapy bic gram-negative bacillary pneumonia. Renal function plays an important role in antimicroThe clinical features of pneumonia in the frail el- bial choice. Although the aminoglycoside antibiotics derly are insidious at onset: confusion or delirium may are among the most effective agents available for the be the prominent presenting sign or symptom, fever treatment of gram-negative infections, the problem of may be absent, chest pain is less common, many pa- their use centers around undertreatment versus toxicity. It is clear that patients with impaired renal functients do not have a cough, and sputum production tion are at highest risk for further renal impairment may be minimal. and may also be at greater risk for the aminoglycoside-related ototoxicity. The combination of imiSkin Infections An important problem in the frail elderly is skin and penemcilastatin is also highly effective against aerosoft tissue infection arising from pressure sores, bic gram-negative rods; unfortunately, toxic levels which are almost entirely preventable with vigilant may cause seizures in patients with impaired renal nursing care [19]. The microbiology of these skin- function. Finally, the third-generation cephalosporins structure infections in the frail elderly is such that a are particularly effective against aerobic gram-negabroad spectrum of infecting micro-organisms can be tive rods among the Enterobacteriaceae; however, anticipated. Evaluation has shown that the most com- with the exception of ceftazidime, they exert only 3G32S
March 23, 1990
The American Journal of Medicine
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SYMPOSIUMON AZTREONAM/JONES
marginal activity against Pseudomonas aeruginosa. In comparison, aztreonam is a monobactam antibiotic developed specifically for the treatment of infection caused by aerobic gram-negative rods. It has an impressive margin of safety and can be easily administered to the frail elderly in a cost-effective manner [25]. With this agent, impaired renal function allows dosage at prolonged time intervals, resulting in a lowering of the cost of pharmacy preparation and nursing administration. When used for broad-spectrum empiric therapy, aztreonam must be combined with an agent or agents effective against aerobic gram-positive bacteria and, when clinically appropriate, anaerobic bacilli; this also holds true for aminoglycoside antibiotics.
COMMENTS Frail elderly people are particularly susceptible to pneumonia, UTIs, and skin infections as a result of defects in the host defenses that protect the surfaces of the body. They are particularly more likely to have gram-negative bacillary infections caused by antibiotic-resistant bacteria. Ethical considerations should be taken into account before choosing to treat, but when empiric treatment is appropriate, an effective antibiotic regimen should be chosen with care. A variety of effective antimicrobial drugs are available, but some of them are difficult to use in this population because of the renal impairment associated with old age.
REFERENCES 1. Tresch DD, Simpson WM Jr, Burton JR: Relationship of longterm care and acute care facilities. The problem of patient transfer and continuity of care. J Am Geriatr Sot 1985; 33: 819426. 2. Irvine PW. Van Buren N. Crosslev K: Causes for hosoitalization for nursine home residents: the role of infection. J Am Geriatr Sot 1984; 2! 103-107. 3. Saltzman RL, Peterson PK: lmmunodeficiency of the elderly. Rev Infect Dis 1987; 9: 1127-1139. 4. Osler W: Pneumonia. in: Osler W, ed. The principles and practice of medicine, 2nd ed.
New York: Appleton and Co., 1987; 563. 5. Terpenning MS, Buggy BP, Kauffman C: Infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: 626-634. 6. Berk SL: Bacterial pneumonia in the elderly: the observations of Sir William Osler in retrospect. J Am Geriatr Sot 1984; 32 (9): 683-685. 7. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Deciding to forgo lie-sustaining treatment: a report on the ethical, medrcal, and legal issues in treatment decisions. Washington, D.C.: United States Government Printing Office, 1983; 90. 8. Brown NK, Thompson DJ: Nontreatment of fever in extended-care facilities, N Engl J Med 1979; 300: 1246-1250. 9. Wanzer SH, Federman DD, Adelstein SJ, et al: The physician’s responsibility toward hopelessly ill patients: a second look. N Engl J Med 1989; 320: 844-849. 10. Cassel CK: Lecture: medical grand rounds: Good Samaritan Hospital, Portland, Ore gon, July 22, 1987. Bloomington, Indiana: Indiana University Press, 1987. 11. The Hastings Center: Guidelines on the termination of life-sustaining treatment and the care of the dying. 1987. 12. Jones SR, Parker D, Liebow B, et at Antibiotic use in nursing homes. Am J Med 1987; 83: 499-501. 13. Dontas AS, Kasviki-Charvati P, Papanayioutou PC, etal: Bacteriuria and surwval in old age. N Engl J Med 1981; 304: 939-943. 14. Nicolle LE, Mayhew WJ, Bryan L: Prospective randomized comparison of therapy and no therapy for asymptomatic bacteriuria in institutionalized elderly women. Am J Med 1987; 83: 27-33. 15. Nicolle LE, Henderson E, Bjornson J, etaPThe association of bacteriuria with resident characteristics and survival in elderly institutionalized men. Ann Intern Med 1987; 105: 682-686. 16. Boscia JA, Abrytyn E, Kay D: Asymptomatic bactenuria in elderly persons: treat or do not treat? (editorial). Ann intern Med 1987; 106: 764-765. 17. Boscia JA, Kobasa WD, Abrutyn E, et a/; Lack of association between bacteriuria and symptoms in the elderly. Am J Med 1986; 81: 979-982. 18. Valenti WM, Trudell RG, Bentley DW: Factors predisposing to oropharyngeal colonization with gram-negative bacilli in the aged. N Engl J Med 1978; 298: 1108-1111. 19. Reuler JB, Cooney TG: The pressure sore: pathophysiology and principles of management. Ann Intern Med 1981; 94: 661-666. 20. Galpin JE, Chow AW, Bayer AS, et al: Sepsis associated with decubitus ulcers. Ann Intern Med 1976; 85: 461-463. 21. Lindeman RD, Tobin J, Shock NW Longitudinal studies on the rate of decline in renal function with aee. J Am Geriatr Sot 1985: 33: 278-285. 22. Shemesh 0;Golbert H, Kriss JP, et al: imitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 830-838. 23. Charleson HA, Bailey RR, Stewart A: Quick prediction of creatinine clearance without the necessity of urine collection. NZ Med J 1980; 92: 425-426. 24. Friedman JR, Norman DC, Yoshikawa T: Correlation of estimated renal function parameters versus 24hour creatinine clearance in ambulatory elderly. J Am Geriatr Sot 1989; 37: 145-149. 25. Jones SR, Kimbrough R: UTls and two new antibiotics in the elderly. Geriatrics 1988; 43: 49-58.
March 23, 1990
The American Journal of Medicine
Volume 88 (suppl 3C)
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Frail and vulnerable elderly patients, recognized primarily by the presence of such disabilities as immobility, incontinence, and dementia, are at particularly high risk for the development of infectious diseases, which are the leading cause of hospitalization in this population. The infectious diseases most often observed in the debilitated elderly are pneumonias, urinary tract infectidns, skin infections, and gastroenteritis, with fever a common, manifestation. Some of the factors identified as contributing to their increased susceptibility include diminishing physiologic functioning; compromised host-defense mechanisms; increased incidence of mechanical risk factors, such as pressure ulcers, indwelling or condom catheters, feeding tubes, and soft tissue injuries; and comorbidities such as soft tissue or pulmonary edema. In addition to the common infecting pathogens found in the general population, these unique compromising factors increase the risk of elderly patients for aerobic gram-negative bacillary infection. Further increasing the therapeutic dilemma are ethical considerations involved in prolonging treatment that might be considered medical intervention beyond what is routine and necessary. Although the decision to treat must be made on an individual basis, studies have not always shown treatment to provide benefits in terms of quality of life. Once it is decided to treat, however, appropriate therapy ,is crucial. One of the most important considerations is renal function, which impacts on effectiveness, toxicity, and cost of therapy and is likely to be diminished in elderly patients. A non-nephrotoxic agent, such as aztreonam, may be a more appropriate therapeutic choice than an aminoglycoside antibiotic in this patient population.
lderly patients are at risk for infectious diseases E for a variety of reasons, including their frequently debilitated condition and the presence of serious underlying disease. Among the elderly, certain subgroups are particularly vulnerable to infection, and the pathophysiology and microbiology of their infections deserve special consideration. In addition, certain ethical questions must be explored in evaluating the clinical aspects and principles of management of the most common infections encountered in this frail and vulnerable population. RECOGNITION OF THE FRAIL AND VULNERABLE ELDERLY The three primary disabilities that define frail and vulnerable eiderly patients are immobility, incor$inence, and dementia; any of these can influence the patient’s placement in nursing homes and other highcare environments. The frail elderly have lower physiologic reserves for coping with intercurrent illness. They may, for example, be vulnerable to influenza A in many seasons, and they are more likely to die from it because they lack the normal homeostatic mechanisms that help a young, vigorous person survive. With influenza, the elderly are more likely to have pneumonia; to become delirious and fall, with resultant hip fractures; or to stay in bed and lose cardiovascular function and tone or develop pressure sores. Infectious diseases are the leading cause of hospital admissions among the frail elderly; they are responsible for hospitalization more often than cardiovascular, gastrointestinal, orthopedic, or any other problems. A study of transfers from the chronic-care facility to the acute-care hospital within one year at Francis Scott Key Hospital of the Johns Hopkins University revealed that 30 percent of the transfers were attributable to infectious disease problems [l]. In another study, Irvine and associates [Z] of the University of Minnesota reported that during a one-year period, 128 patients from nursing homes and 320 fro? &be geriatric clinic were hospitalized. As in the Johns Hopkins study, the leading cause of hospitalization of patients from the nursing homes was infectious diseases, which accounted for approximately 25 percent, whereas only 12 percent of hospitalizations from the geriatric clinic were due to infectious diseases. In both studies, pneumonia, urinary tract infections (UTIs), skin infections, and gastroenteritis were the principal infectious causes, with fever a common manifestation. FACTORS INFLUENCING THE VULNERABILITY OF THE ELDERLY Pathophysiologic Features of Infection
From the Good Samaritan Hospital, Oregon Health Sciences Unlverslty, Portland, Oregon. Requests for reprints should be addressed to Stephen R. Jones, M.D., Depatiment of Medicine, Oregon Health Sciences University, and Department of Medicine, Good Samaritan Hospital and Medlcal Center, 1015 NW 22nd Avenue, Portland, Oregon 97210.
3c-30s
March 23, 1990
The American Journal of Medicine
Many geriatric textbooks discuss accepted trends for measuring diminishing physiologic functions in the elderly, including cardiac index, glomerular filtration rate, vital capacity, and more. Other factors, however, also contribute to the susceptibility of the el-
Volume 88 (suppl 3C)
SYMPOSIUM
derly to infection. The host-defense mechanisms of this group, for example, may be markedly compromised. Host-defense mechanisms can be divided into three categories: those that operate at body surfaces, extracellular fluid factors, and cellular factors. Bodysurface factors include skin, mucous membranes, cough reflex, and the normal motility of the gastrointestinal and genitourinary tracts, as well as the more sophisticated host-defense mechanisms such as complement, T lymphocytes, immunoglobulins, and phagocytic cells. Despite extensive investigation, no consistent defects have been identified that appear to correlate clinically with the common infectious diseases of the elderly [3]. It appears that mechanical risk factors, rather than sophisticated host-defense defects, are responsible for impairment of body-surface functions. These factors include pressure ulcers, indwelling catheters, condom catheters, feeding tubes, and soft tissue injuries that result from handling of immobile patients by attendants. Important comorbidities common in the elderly also predispose them to infection. Soft tissue edema from lymphatic or venous stasis, heart disease, or low albumin, for example, may lead to cellulitis, and pulmonary edema is an important risk factor for development of pneumonia. Microbiologic Features of Infections
The usual site-pathogen rules for the general population remain valid for the frail elderly: Stu~hyZococcus is still the most common cause of skin infection; the pneumococcus, the most common cause of pneumonia; and Escherichia coli the most common pathogen involved in UTIs. The mucosal and skin-surface alterations discussed, as well as the source of the infectious pathogens, increase the risk for aerobic gramnegative bacillary infections in the frail elderly, who also are more likely to acquire gram-negative bacillary pneumonia, skin infections, and UTIs caused by antibiotic-resistant bacteria. PRESENTATION OF INFECTION The tendency for the manifestation of infection in the elderly to be subtle and nonspecific has been recognized for some time: In 1897, Osler [4] stated that: in the old and debilitated, a knowledge that the onset of pneumonia is insidious and that the symptoms are ill defined and latent should place the practitioner on his guard and make him very careful in the examination of the lungs in doubtful cases. In the study by Irvine and associates [Z], twice as many patients from the nursing homes as from the clinic had admitting complaints that were nonspecific for their primary diagnosis. In another study of infective endocarditis in three different age groups (younger than age 40, 40 to 60 years of age, and older than 60 years), it was revealed that the initial evaluation by admitting physicians mentioned endocarditis as a diagnostic possibility in 76 percent of those under age 40 but in only 32 percent of those older than age 60 151. Diagnosis of endocarditis, as well as other important infectious diseases, becomes more difficult as patients get older. ETHICAL CONSIDERATIONS Professionals in hospitals may inappropriately apply high technology to stop the perhaps appropriate
ON AZTREONAM / JONES
and inevitable demise of the frail elderly. According to Osler [6]: Pneumonia may well be called the friend of the aged. Taken off by an acute, short, often painless illness, the old escape those cold gradations of decay that make the last state of all so distressing. More distressing than fatal pneumonia to the elderly and their families is the anticipation of sustaining not a cold, slow death, but an intense slow death in a critical-care setting. Ethical dilemmas are unavoidable in selecting treatment for elderly patients. Antibiotics, for example, must be considered among the life-sustaining treatments, and there is legal precedent that such therapy can be viewed as medical intervention beyond what is routine and necessary. In 1983, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical Research 171 stated that: the Commission has found no particular treatments, including such ordinary hospital interventions as parenteral nutrition, hydration, or antibiotics, to be universally warranted. Nevertheless, the decision to forgo particular life-sustaining treatments is not a ground to withdraw all care, especially when care is needed to ensure patients’ comfort, dignity, and self-determination. Comfort, dignity, and self-determination are primary; antibiotics and other life-sustaining measures are optional. It may therefore be permissible and appropriate to withhold such treatment when such a course of action is decided on by directive of the patient, his family, and/or the clinician. In fact, studies have shown that this has been a standard of practice [8,9]. Clearly, an analytic framework is crucial for making decisions in the face of such an ethical dilemma. Cassel [lo] has suggested a series of steps that may be useful in reaching the annronriate decision: 1. Collect and be familiar v&hall data pertaining to the clinical problem. 2. Examine the motives of all of those who will be involved in making the decision-the family or person who has legal responsibility for the patient, as well as those involved in patient care. 3. Consider ethical principles. 4. Rank the principles. Examine the consequences of making the decision. 8: Make the decision. Most physicians have, at best, only rudimentary skills and knowledge for considering ethical principles. Among many sources, a 1987 publication from the Hastings Center 1111 provides guidelines on the termination of life-sustaining therapy that are quite useful; it contains a section on the use of antibiotics and other life-sustaining drugs that is particularly appropriate for these considerations. An investigation of the use of antibiotics in several long-term care facilities in Portland, Oregon, evaluated the majority (51 percent) of antibiotic prescriptions as inappropriate; 49 percent were considered appropriate 1121. Similar to most studies, the most common use of antibiotic therapy in this study cohort was for infections of the urinary tract (more than half of the 120 infections treated with antibiotics), respiratory tract, and skin. Trimethoprim was the drug most
March 23, 1990
The American Journal of Medicine
Volume 88 (suppl 3C)
3c-31s
SYMPOSIUM
ON AZTREONAM / JONES
frequently considered to have been used correctly. This study was conducted in 1986, and there have been advances in antimicrobial treatment since that time that may allow more appropriate treatment. SPECIFIC INFECTIONS THAT AFFECT THE ELDERLY UTIs, pneumonias, and skin and soft tissue infection most commonly affect the elderly. Urinary Tract infections
UTIs in the frail elderly can be categorized as follows: asymptomatic infections, either with or without a catheter, and symptomatic infections. In asymptomatic patients who have bacteriuria, treatment is generally not helpful. Although bacteriuric frail elderly patients die earlier than do such patients who are nonbacteriuric, a series of blinded, randomized controlled studies of bacteriuric frail elderly in nursing homes has not shown treatment to decrease morbidity or mortality [13-151. Another study has evaluated elderly persons who are less frail to determine whether eradicating the bacteriuria would make them more mobile, more continent, and less demented [16,17]. Unfortunately, the answer was still no. Asymptomatic bacteriuria in the elderly is not a public health menace. Only symptomatic infection requires investigative and therapeutic management.
mon isolates from these ulcers are among the Enterobacteriaceae, most frequently Proteus spp., although Staphylococcus aureus is also common. Importantly, Bacteroides frugilis is the most common isolate from the bloodstream, although Proteus is the most common aerobic isolate found in the bloodstream [20]. TREATMENT CONSIDERATIONS IN ELDERLY PATIENTS Clearly, gram-negative aerobic bacteria are an important cause of the most common infections encountered in elderly patients, and if these infections are to be treated, appropriate antimicrobial therapy must be carefully chosen. Currently, a variety of highly efficacious parenteral antimicrobial agents are available for treating aerobic gram-negative bacilli. These include aminoglycosides, third-generation cephalosporins, imipenem/cilastatin, and aztreonam, among others. When choosing an antibiotic regimen for this population, one of the most important factors to consider is renal function, which in turn dictates effectiveness, toxicity, and cost of treatment. Renal Function in the Elderly
Renal function persistently declines with age [21]. Although deterioration of renal function is likely to be more rapid in association with such disease-related conditions as diabetes mellitus, hypertension, and athLower Respiratory Tract infections erosclerosis, there is no doubt that it is age-related as Important factors are associated with pneumonia in well. the frail elderly. First, frail elderly patients are more A number of principles apply to the measurement of prone to aspiration and less likely to clear bacteria renal function in the elderly: (1) Serum creatinine once the lower respiratory tract is invaded than less alone is a poor measurement of renal function because frail persons. This may be attributed to a commonly of the progressively diminished muscle mass with age. poor cough reflex. The prevalence of aerobic gram- (2) Formal measurement of glomerular filtration is negative rods in the oropharynx is an important ante- tedious as well as retrospective, and other measurecedent to the development of lower respiratory tract ments are impractical. Timed creatinine clearance, for infection in the frail elderly. The prevalence of aerobic example, is progressively invalidated as the glomerugram-negative colonization of the oropharynx has lar filtration rate decreases, increasing proportionbeen compared in healthy and ill subjects and reveals ately the tubal excretion of creatinine [22]. (3) A simthat the incidence of gram-negative-rod colonization is ple estimation of the glomerular filtration rate using only 1 percent in healthy people, whereas between 24 the Cockcroft-Gault formula (140 minus age, divided and 50 percent of patients in intensive care units har- by serum creatinine) can indicate those patients with bor gram-negative rods in high numbers. In compariimportantly diminished renal function [23]. The result son, in an elderly nursing home population, an overall can then be adjusted for body weight of the patient by prevalence of 3’7 percent has been documented, with multiplying by the patient’s weight, divided by ‘72 kg. an incidence of 50 percent among the bedridden 1181. It is not necessary to adjust for gender in frail elderly Aerobic gram-negative rods are commonly present in patients because of the progressive decrease in muscle the oropharynx of the frail elderly, and if aspiration mass in elderly men [24]. occurs, these bacteria are found in high numbers. The frail elderly are particularly prone, therefore, to aero- Impact of Renal Function on Choice of Therapy bic gram-negative bacillary pneumonia. Renal function plays an important role in antimicroThe clinical features of pneumonia in the frail el- bial choice. Although the aminoglycoside antibiotics derly are insidious at onset: confusion or delirium may are among the most effective agents available for the be the prominent presenting sign or symptom, fever treatment of gram-negative infections, the problem of may be absent, chest pain is less common, many pa- their use centers around undertreatment versus toxicity. It is clear that patients with impaired renal functients do not have a cough, and sputum production tion are at highest risk for further renal impairment may be minimal. and may also be at greater risk for the aminoglycoside-related ototoxicity. The combination of imiSkin Infections An important problem in the frail elderly is skin and penemcilastatin is also highly effective against aerosoft tissue infection arising from pressure sores, bic gram-negative rods; unfortunately, toxic levels which are almost entirely preventable with vigilant may cause seizures in patients with impaired renal nursing care [19]. The microbiology of these skin- function. Finally, the third-generation cephalosporins structure infections in the frail elderly is such that a are particularly effective against aerobic gram-negabroad spectrum of infecting micro-organisms can be tive rods among the Enterobacteriaceae; however, anticipated. Evaluation has shown that the most com- with the exception of ceftazidime, they exert only 3G32S
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SYMPOSIUMON AZTREONAM/JONES
marginal activity against Pseudomonas aeruginosa. In comparison, aztreonam is a monobactam antibiotic developed specifically for the treatment of infection caused by aerobic gram-negative rods. It has an impressive margin of safety and can be easily administered to the frail elderly in a cost-effective manner [25]. With this agent, impaired renal function allows dosage at prolonged time intervals, resulting in a lowering of the cost of pharmacy preparation and nursing administration. When used for broad-spectrum empiric therapy, aztreonam must be combined with an agent or agents effective against aerobic gram-positive bacteria and, when clinically appropriate, anaerobic bacilli; this also holds true for aminoglycoside antibiotics.
COMMENTS Frail elderly people are particularly susceptible to pneumonia, UTIs, and skin infections as a result of defects in the host defenses that protect the surfaces of the body. They are particularly more likely to have gram-negative bacillary infections caused by antibiotic-resistant bacteria. Ethical considerations should be taken into account before choosing to treat, but when empiric treatment is appropriate, an effective antibiotic regimen should be chosen with care. A variety of effective antimicrobial drugs are available, but some of them are difficult to use in this population because of the renal impairment associated with old age.
REFERENCES 1. Tresch DD, Simpson WM Jr, Burton JR: Relationship of longterm care and acute care facilities. The problem of patient transfer and continuity of care. J Am Geriatr Sot 1985; 33: 819426. 2. Irvine PW. Van Buren N. Crosslev K: Causes for hosoitalization for nursine home residents: the role of infection. J Am Geriatr Sot 1984; 2! 103-107. 3. Saltzman RL, Peterson PK: lmmunodeficiency of the elderly. Rev Infect Dis 1987; 9: 1127-1139. 4. Osler W: Pneumonia. in: Osler W, ed. The principles and practice of medicine, 2nd ed.
New York: Appleton and Co., 1987; 563. 5. Terpenning MS, Buggy BP, Kauffman C: Infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: 626-634. 6. Berk SL: Bacterial pneumonia in the elderly: the observations of Sir William Osler in retrospect. J Am Geriatr Sot 1984; 32 (9): 683-685. 7. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Deciding to forgo lie-sustaining treatment: a report on the ethical, medrcal, and legal issues in treatment decisions. Washington, D.C.: United States Government Printing Office, 1983; 90. 8. Brown NK, Thompson DJ: Nontreatment of fever in extended-care facilities, N Engl J Med 1979; 300: 1246-1250. 9. Wanzer SH, Federman DD, Adelstein SJ, et al: The physician’s responsibility toward hopelessly ill patients: a second look. N Engl J Med 1989; 320: 844-849. 10. Cassel CK: Lecture: medical grand rounds: Good Samaritan Hospital, Portland, Ore gon, July 22, 1987. Bloomington, Indiana: Indiana University Press, 1987. 11. The Hastings Center: Guidelines on the termination of life-sustaining treatment and the care of the dying. 1987. 12. Jones SR, Parker D, Liebow B, et at Antibiotic use in nursing homes. Am J Med 1987; 83: 499-501. 13. Dontas AS, Kasviki-Charvati P, Papanayioutou PC, etal: Bacteriuria and surwval in old age. N Engl J Med 1981; 304: 939-943. 14. Nicolle LE, Mayhew WJ, Bryan L: Prospective randomized comparison of therapy and no therapy for asymptomatic bacteriuria in institutionalized elderly women. Am J Med 1987; 83: 27-33. 15. Nicolle LE, Henderson E, Bjornson J, etaPThe association of bacteriuria with resident characteristics and survival in elderly institutionalized men. Ann Intern Med 1987; 105: 682-686. 16. Boscia JA, Abrytyn E, Kay D: Asymptomatic bactenuria in elderly persons: treat or do not treat? (editorial). Ann intern Med 1987; 106: 764-765. 17. Boscia JA, Kobasa WD, Abrutyn E, et a/; Lack of association between bacteriuria and symptoms in the elderly. Am J Med 1986; 81: 979-982. 18. Valenti WM, Trudell RG, Bentley DW: Factors predisposing to oropharyngeal colonization with gram-negative bacilli in the aged. N Engl J Med 1978; 298: 1108-1111. 19. Reuler JB, Cooney TG: The pressure sore: pathophysiology and principles of management. Ann Intern Med 1981; 94: 661-666. 20. Galpin JE, Chow AW, Bayer AS, et al: Sepsis associated with decubitus ulcers. Ann Intern Med 1976; 85: 461-463. 21. Lindeman RD, Tobin J, Shock NW Longitudinal studies on the rate of decline in renal function with aee. J Am Geriatr Sot 1985: 33: 278-285. 22. Shemesh 0;Golbert H, Kriss JP, et al: imitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 830-838. 23. Charleson HA, Bailey RR, Stewart A: Quick prediction of creatinine clearance without the necessity of urine collection. NZ Med J 1980; 92: 425-426. 24. Friedman JR, Norman DC, Yoshikawa T: Correlation of estimated renal function parameters versus 24hour creatinine clearance in ambulatory elderly. J Am Geriatr Sot 1989; 37: 145-149. 25. Jones SR, Kimbrough R: UTls and two new antibiotics in the elderly. Geriatrics 1988; 43: 49-58.
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