CHAPTER 44—INFECTIOUS DISEASES
DIAGNOSIS AND MANAGEMENT OF INFECTIONS
Infection is the major cause of mortality in 40% of those aged 65 years and older, and it contributes to death in many others. Infection is also a significant cause of morbidity in older adults, often exacerbating underlying illness or leading to hospitalization. Four of the top twenty diagnosis-related groups paid by Medicare are infection-related diagnoses (pneumonia, number 2; urinary tract infections, number 14; septicemia, number 15; and other respiratory infections, number 17). Further, because of their increased susceptibility to infection, older adults often herald the arrival of new infections or the return of annual epidemics. Associations of infection and inflammation with age-related chronic diseases suggest that infectious diseases may play an even larger role in the morbidity and mortality of the elderly population than previously realized. This chapter explores the biologic, cultural, and societal factors that influence susceptibility to infection, the presentation of disease, and the management of infections in elderly patients.
Fundamental alterations in the immune response occur with aging in large measure because of comorbidities but also because of age-related declines in immunity, a phenomenon known as immune senescence (Table 44.1). The main features of immune senescence are depressed T-cell responses and T-cell–macrophage interactions (clinically reflected as delayed-type hypersensitivity responses), but deficits of innate immunity are increasingly being recognized, particularly in frail elderly patients.
Although age itself influences immune function, comorbidities have the greatest impact on innate immune function and nonspecific host-resistance factors; for example, skin integrity and cough or gag reflexes are local defense mechanisms that are often impaired. Perhaps the best example is chronic obstructive pulmonary disease, in which impaired mucociliary clearance and alveolar macrophage dysfunction are likely to be factors that increase the risk of lower respiratory tract infection. Comorbid diseases also indirectly complicate infections in elderly persons. For example, community-acquired pneumonia in otherwise healthy patients under age 50 is typically treated on an outpatient basis and rarely causes mortality; however, in elderly patients with community-acquired pneumonia and multiple comorbid conditions, the greatly increased risk of morbidity and mortality often necessitates hospitalization. Furthermore, cognitive impairment and other barriers to adherence may increase the difficulty of treating elderly patients, increasing complications and costs.
A major influence on immune function in the older person is nutritional status. Global (protein and calorie) undernutrition is present in 30% to 60% of persons aged 65 years or older on admission to the hospital. In the outpatient arena, 11% of older adults suffer from undernutrition, 90% of which is due to reversible underlying conditions (depression, poorly controlled diabetes mellitus, medication side effects). Delayed wound healing, increased risk of nosocomial infection, extended lengths of hospital stay, and increased mortality are all associated with malnutrition. Even mildly undernourished older adults (those with a serum albumin of 3.0 to 3.5 g/dL) have evidence of immune compromise, poor vaccine responses, and diminished cytokine responses to specific challenges. Nutritional interventions may boost immune function in some older adults, but this remains controversial. Some studies suggest a clinical benefit, particularly in those with subclinical nutritional deficiencies, whereas others do not. Differences in study design, population enrolled, duration of follow-up, and definitions of infection (self-reported versus physician diagnosed) may account for many of these differences. (See Malnutrition.)
Institutionalization places elderly persons at greatly increased risk for epidemic disease such as influenza. Widespread antibiotic use also increases their risk for acquiring diseases caused by more resistant organisms. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multiply resistant gram-negative rods are more common causes of infection in institutionalized elderly persons. Resistance is fostered in the nursing home by debilitated hosts, close proximity of residents, and difficulties in implementing infection-control measures in long-term care, as well as high levels of antibiotic use.
It has long been recognized that older adults may present without typical signs and symptoms, even in the face of very significant infection. Fever, the most readily recognized feature of infection, may be absent in 30% to 50% of frail older adults with serious infections, even pneumonia or endocarditis. The cause of impaired febrile responses in older adults is incompletely understood, but diverse mechanisms of thermoregulation are involved, including blunted thermogenesis by brown adipose tissue.
Because of the altered febrile response to infection, many authors have suggested a redefinition of fever in older adults. Given the sensitivity, specificity, and positive and negative predictive values, fever in elderly nursing-home residents can be redefined appropriately as a temperature > 2°F (1.1°C) over baseline (if a baseline is available) or, perhaps more practically, an oral temperature > 99°F (37.2°C) or a rectal temperature > 99.5°F (37.5°C) on repeated measures. This definition of fever has a sensitivity of 82.5% in nursing-home residents, and the specificity remains high at 89.9% (Table 44.2). Although these data were generated in a trial of frail older veteran men in a nursing home, it would seem reasonable to apply the same definitions to frail older adults of either gender in the community. However, the performance characteristics of this definition of fever in otherwise healthy older adults has not been validated.
The absence of fever is only one way that infectious diseases may present atypically in the elderly person. For example, infective endocarditis may be heralded by a nonspecific decline in baseline functional status, such as confusion or falling. Subsequent anorexia and decreased oral intake may follow, and exacerbation of an underlying illness (eg, atrial fibrillation) may become the predominant feature. Cognitive impairment further contributes to the atypical presentation of infections in older adults. Many cognitively impaired older patients are unable to communicate symptoms accurately, and clinicians must be ready to pursue objective assessments such as laboratory and radiologic evaluations at a lower threshold, unless advance directives indicate otherwise.
Drug distribution, metabolism, excretion, and interactions may be altered with age. Aging in the absence of any comorbid disease is associated with a reduction in renal function, and reductions in antibiotic dose may be required in the elderly patient. (See Pharmacotherapy.) Furthermore, antibiotic interactions occur with many medications commonly prescribed for elderly persons. Digoxin, warfarin, oral hypoglycemic agents, theophylline, antacids, lipid-lowering agents, antihypertensive medications, and H2-receptor antagonists all have significant interactions with commonly prescribed antibiotics. Drug concentrations can increase (eg, enhanced digoxin toxicity associated with macrolides, tetracyclines, and trimethoprim) or decrease (eg, reduced absorption of some fluoroquinolones with antacids) with concomitant drug administration. Atrophic gastritis, a common problem in older adults, and H2 blockers or proton-pump inhibitors can reduce the absorption of some antibiotics, such as ketoconazole or itraconazole. Finally, adherence to prescribed regimens may be limited as a consequence of poor cognitive function, impaired hearing or vision, use of multiple medications, and financial constraints.
The choice and timing of antibiotics may also be important in the treatment of older infected adults. In sepsis, a preponderance of data suggests that initially broad coverage is warranted, since outcomes (mortality, length of stay in intensive care) are improved when the offending organism is covered by the initial antibiotic regimen. In older adults with pneumonia, data suggest that delaying initiation of therapy 4 or more hours after admission to the hospital is associated with an increased risk of mortality. However, these and similar data in other infectious syndromes and the atypical presentation of infection noted above often leads to early initiation of antimicrobials in older adults, particularly in long-term care. However, in long-term care, up to 75% of antibiotic use may be inappropriate. The use of strict, minimum criteria for initiation of antimicrobials in long-term care is most likely to reduce inappropriate antibiotic use without jeopardizing patient safety (Table 44.3).
Bacteremia is a common cause of hospitalization for older patients. Older patients with bacteremia are less likely than their younger counterparts to have chills or sweating, and fever is commonly absent. Gastrointestinal and genitourinary sources of bacteremia are more common; thus, the causative bacteria are more likely to be gram-negative rods.
Bacteremia carries a poor prognosis in older adults. For example, nosocomial gram-negative bacteremia carries a mortality rate of 5% to 35% for young adults, but in older adults the mortality rate is 37% to 50%. Major contributing factors include coexisting diseases that reduce physiologic reserve and the more common use of invasive devices (eg, intravenous or urinary catheters) that make eradication of organisms difficult.
The management of bacteremia and sepsis in older and younger patients is similar. Rapid administration of appropriate antibiotics aimed at the most likely sources is essential. The use of activated protein C as adjunctive therapy in septic older adults had raised concern about increased bleeding. However, a recent analysis of patients aged 75 and over enrolled in a randomized trial of activated protein C in sepsis demonstrated preservation of the survival benefit in older adults despite a slightly increased risk of serious bleeding.
Patients aged 65 years and older account for more than 50% of all pneumonia cases, and annual hospitalization rates for pneumonia range from 12 per 1000 among community-dwelling adults aged 75 and older to 32 per 1000 among nursing-home residents. In fact, the cumulative 2-year risk of pneumonia for long-term-care residents is approximately 30%. Pneumonia mortality in older adults is three to five times that of young adults, but the rate is profoundly influenced by comorbidity. Comorbidity is the strongest independent predictor of mortality in community-acquired pneumonia in older adults, with a relative risk of 4.1 (in the article that determined this relative risk, comorbidity was defined as cancer, collagen vascular disease, or advanced liver disease). Other independent risk factors include age of 85 years and older, debility (decreased motor function), serum creatinine > 1.5 mg/dL, and the presence of hypothermia (< 36.1°F), hypotension (< 90 mm Hg systolic), or tachycardia (> 110 beats per minute) on admission. Long-term follow-up data also suggest that community-acquired pneumonia in older adults indicates a higher risk of subsequent all-cause mortality over the next 12 years as a consequence of both recurrent pneumonia (relative risk 2.1 [1.3 to 3.4]) but also cardiovascular disease (relative risk 1.4 [1.0 to 1.9]).
The causes of pneumonia in younger and elderly adults differ. In elderly patients, Streptococcus pneumoniae is still the predominant organism, but gram-negative bacilli (eg, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella spp.) are much more common than in younger adults, particularly in patients with chronic obstructive pulmonary disease or who reside in long-term-care facilities. S. aureus and respiratory viruses are also common causes of community-acquired pneumonia in nursing-home residents (Figure 44.1).
Pneumonia therapy has changed significantly in the past few years because of the emergence of resistant bacteria, particularly drug-resistant S. pneumoniae, leading many practitioners to rely heavily on fluoroquinolones, even for routine community-acquired pneumonia. This practice, however, has led to increased rates of fluoroquinolone resistance in several areas of the world, and some fluoroquinolones can have significant adverse effects, including dizziness and cardiac conduction abnormalities (QT prolongation), that may limit their use in certain older adults. The current Infectious Diseases Society of America treatment guidelines for community-acquired pneumonia suggest the following as first-line therapy in adults over the age of 60 with or without comorbidity: a β-lactam and β-lactamase combination or advanced-generation cephalosporin (ceftriaxone or cefotaxime) with or without a macrolide. Alternatively, one of the newer fluoroquinolones with enhanced activity against S. pneumoniae (levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin) may be used. Given the resistance already emerging to fluoroquinolones, it is prudent to use these drugs only in situations with highest risk for drug-resistant S. pneumoniae or other resistant organisms. In the outpatient setting, this is limited to residents of long-term-care facilities or patients with marked chronic obstructive pulmonary disease (FEV1 < 30% predicted). In the inpatient setting, the sicker the patient (ie, the closer to needing intensive care), the stronger the justification for use of a fluoroquinolone. This is true because the margin for error is small, fluoroquinolones are currently the most effective therapy for drug-resistant S. pneumoniae, they are effective against most gram-negative bacilli, and they can be used to treat atypical organisms such as such as Legionella spp. that are more likely in the intensive-care setting.
Nursing-home acquired pneumonia (NHAP) or hospital acquired pneumonia (HAP) in older adults requires more broad initial therapy than community-acquired pneumonia because of the broader spectrum of organisms causing infection (see Figure 44.1). In the nursing-home setting, polymicrobial infection, often due to aspiration, and S. aureus are much more common than in the community setting. In the hospital setting, gram-negative bacilli predominate, but S. aureus is more common as well and is more likely to affect specific antibiotic choices because of resistance. Outcomes data suggest that response to therapy is greater when the initial antibiotic regimen covers the offending agent. Thus, initial regimens should be broadly inclusive, followed by step-down therapy to more narrow coverage if the causative agent is identified. Importantly, if patients are known to be colonized with methicillin-resistant S. aureus (MRSA), initial regimens should include vancomycin or linezolid until MRSA is excluded as the cause. Further, data suggest that patients with clinically improving HAP not caused by nonfermenting gram-negative bacilli (eg, Pseudomonas, Stenotrophomonas) can be treated with shorter courses of antibiotics, 7 or 8 days, rather than the 2 weeks commonly employed in the past. Shorter courses (8 days versus 15 days) of antibiotics are associated with equivalent efficacy and less antibiotic resistance.
The prevention of pneumonia in older adults is a complex issue, and a multipronged approach is most likely to be effective. Immunization of at-risk persons is far and away the most well-studied measure (see Prevention). In addition to vaccines, smoking cessation and aggressive treatment of comorbidities (eg, minimizing aspiration risk in post-stroke patients, limited use of sedative hypnotics) may reduce the risk of infection. Finally, system changes with attention to infection control (isolation, cohorting, skin testing for tuberculosis with purified protein derivative [PPD], and immunization policies) may be particularly effective in the nursing home.
Influenza results in approximately 40,000 deaths annually in the United States, and nearly all of these deaths occur in the older adult population. The clinical syndrome of influenza is easily recognized by most clinicians, particularly in the setting of local activity or outbreak settings frequently seen in the nursing home. Annual influenza vaccine is 60% to 80% efficacious in older adults for preventing severe disease, hospitalization, and death. Therefore, annual immunization is recommended for all adults over the age 50, and for anyone of any age who wishes to reduce the risk of serious influenza.
Several drugs are available for treatment and prophylaxis of influenza. M2 inhibitors (amantadine and rimantadine) block the M2 ion channel of influenza and are effective only against influenza A. Amantadine is particularly difficult to use in older adults because of the extensive dose adjustments required for small changes in kidney function and marked adverse effects, particularly central nervous system symptoms. In contrast, neuraminidase inhibitors (zanamivir and oseltamivir) are effective against both influenza A and B; they inhibit the virus by interference with an essential enzyme, neuraminidase, that cleaves sialic acid to expose host cell receptors for the virus. Oseltamivir, a capsule, is preferred over zanamivir in older adults because zanamivir must be inhaled, and it is difficult for many older adults to properly use the product. Treatment of influenza is effective if initiated in the first 48 hours, but it is most effective if initiated within 24 hours of symptom onset. Amantadine, rimantadine, zanamivir, and oseltamivir also can be used for prevention in outbreak situations (eg, in long-term care) when combined with appropriate vaccination strategies.
Urinary tract infection (UTI) is among the most common of clinical illnesses in older adults, with an incidence of 10.9 per 100 person years in men and 14 per 100 person years in women age 65 and older. As in young adults, gram-negative bacilli (eg, Escherichia coli, Enterobacter spp., Klebsiella spp., Proteus spp.) are most common, but there is an increase in more resistant isolates, such as Pseudomonas aeruginosa, and in gram-positive organisms, including enterococci, coagulase-negative staphylococci, and Streptococcus agalactiae (group B strep). In patients with indwelling catheters, the microbes listed still predominate, but it is also common to encounter additional organisms, including enterococci, S. aureus, and fungi, particularly Candida spp. The organisms colonizing urinary catheters commonly develop biofilms and are difficult to clear with the same urinary catheter in place.
Up to 15% of women in the community and 40% of women in nursing homes will have asymptomatic bacteruria; the incidence in men is approximately half that for women. Rates are even higher with the use of condom catheters (87%) or Foley catheters (nearly 100%). Numerous studies have suggested that there is no clinical benefit from the treatment of asymptomatic bacteruria and that treatment is associated with significant adverse effects, expense, and the potential for selection of resistant organisms. Thus, no treatment is recommended. The clinical difficulty faced almost daily by clinicians is deciding what is symptomatic. The presentation of infection can be quite subtle in older adults, and a change in functional status often prompts the collection of a urine specimen even in the absence of fever, dysuria, or other typical clinical features. However, since no controlled trial has ever shown a decreased incidence of urosepsis or mortality with antibiotic treatment of asymptomatic bacteruria, a period of observation rather than a therapeutic trial would seem most prudent when symptoms are not clearly related to bacteruria.
In contrast to asymptomatic bacteruria, symptomatic UTI does require therapy. Therapy is based on the location of infection (upper versus lower tract disease) and likely causative agent. Lower tract UTI (cystitis), characterized by dysuria, frequency, and urgency (note: not fever, which generally indicates upper tract disease), is often treated in young women for 1 to 3 days, and recent data suggest 3 days of therapy is sufficient for uncomplicated cystitis in older women. Randomized trials in older women indicate that fluoroquinolones are more efficacious than trimethoprim-sulfamethoxazole (TMP-SMX), likely because of E. coli TMP-SMX resistance rates of 10% to 20% in most areas of the country. Other reasonable choices in some settings include amoxicillin (particularly for enterococcal infection) and first-generation cephalosporins in the patient with multiple antibiotic intolerances. Culture is not required unless first-line therapy fails.
Upper UTI (pyelonephritis), characterized by fever, chills, nausea, and flank pain and commonly accompanied by lower tract symptoms, requires more prolonged therapy, 7 to 21 days. Because of the excellent bioavailability of many antibiotics, particularly the fluoroquinolones, intravenous therapy is not essential if the patient can tolerate oral medications. A study comparing fluoroquinolones with TMP-SMX for upper tract UTI in younger women (aged 18 to 58) suggests that fluoroquinolones are more effective (microbiologic cure rate 99% versus 89% for TMP-SMX; clinical cure rates 96% versus 83%, respectively) because of the presence of TMP-SMX–resistant organisms. This is likely to be true in older adults as well. Intravenous administration of antibiotics remains the standard of care for patients with suspected urosepsis, those with upper tract disease due to relatively resistant bacteria such as enterococci, or those unable to tolerate oral medications. Culture and sensitivity data are more useful in guiding antimicrobial therapy in upper tract UTIs than in lower tract disease and should be obtained in most cases.
Prophylactic antibiotics intended to prevent frequently recurrent UTIs in older women are not recommended because of the high incidence of the development of resistant organisms. Several measures may decrease the frequency of recurrence, including intravaginal or systemic estrogen replacement that changes the vaginal flora, thus reducing the risk of UTI, or perhaps ingestion of at least 300 mL of cranberry juice each day, though data in support of these measures remain preliminary.
Prostatic disease (primarily hyperplasia) or functional disability, such as autonomic neuropathy from diabetes mellitus with incomplete bladder emptying, account for the majority of both lower and upper UTIs in elderly men. Thus, short-course therapy for UTIs in elderly men is inappropriate and should be avoided. A minimum of 14 days of therapy should be provided, and if prostatic involvement is suspected (ie, acute or chronic prostatitis), at least 6 weeks of therapy is usually required. The causative organisms and treatment choices are similar to those outlined above for elderly women. Fluoroquinolones and TMP-SMX are most widely used when prostatic involvement is suspected and culture data confirms the organism’s susceptibility because, of the available agents, these two penetrate the prostate most adequately. Because treatment for all UTIs in men is generally longer than in women and the prostate is a common reservoir for recurrent UTIs, culture and sensitivity data should guide therapy for virtually all UTIs in men.
Worldwide, approximately 1.7 billion persons are infected with Mycobacterium tuberculosis (MTB), 16 million in the United States. Adults aged 65 and older account for one fourth of all active tuberculosis cases in the United States. The vast majority of active MTB in older adults occurs in community-dwelling elderly persons, but the rate of infection in long-term-care residents is much higher: skin-test studies show prevalence rates of skin-test reactivity in the range of 30% to 50%. This high prevalence is due to MTB exposure in the early 1900s, when it was estimated that 80% of all persons were infected with MTB by the age of 30. Most active cases of tuberculosis in older adults are, therefore, due to reactivation disease, but primary infection may account for 10% to 20% of cases and is of particular concern in nursing-home outbreaks.
As with most other infections, tuberculosis may not present in classic fashion (cough, sputum, fever, night sweats, weight loss) in the elderly patient. Often fatigue, anorexia, decreased functional status, or low-grade fever are the presenting manifestations. Most tuberculous disease in elderly persons occurs with lung involvement (75%), and pneumonic processes in older adults, particularly those that occur in a postacute manner, should raise a high index of suspicion for MTB. Older adults are more likely than their younger counterparts to have extrapulmonary disease. Other sites include miliary (disseminated) disease, tuberculous meningitis or osteomyelitis, and urogenital disease, but virtually any body structure can be involved, and that organ system can account for the major presenting symptom.
A diagnosis of active disease usually requires isolation of the organism from sputum, urine, or other clinical specimen. Current techniques have improved the speed of diagnosis, particularly for identifying the species of Mycobacterium after isolation. This is now typically accomplished within 24 hours of obtaining a positive culture by use of DNA probes. Direct polymerase chain reaction of clinical specimens or other rapid diagnostic techniques are not available or reliable in most local laboratories, but such tests can be obtained in research settings. They are most likely to be helpful for establishing a diagnosis from cerebrospinal or pleural fluid, which yields positive cultures in only 10% to 15% of cases.
The most confusing area of MTB diagnostics for most practitioners is the interpretation of the results of PPD skin tests. In all populations, induration of ≥ 15 mm 48 to 72 hours after placement of a 5-tuberculin-unit PPD indicates a positive test. Induration ≥ 10 mm is considered a positive test in nursing-home residents, recent converters (previous PPD < 5 mm), immigrants from countries with high endemicity of MTB, underserved populations in the United States (homeless persons, black Americans, Hispanic Americans, and Native Americans), and persons with specific risk factors (gastrectomy, > 10% below ideal body weight, chronic kidney failure, diabetes mellitus, or immune suppression, including that caused by corticosteroids or malignancy). In patients infected with human immunodeficiency virus (HIV), those with a history of close contact with persons with active MTB, and those with chest radiographs consistent with MTB, ≥ 5 mm induration is considered a positive PPD test. Anergy panel testing in conjunction with PPD testing is of little value and is not recommended.
Long-term-care facilities should employ a two-step procedure for PPD testing during the initial evaluation of residents. Two-step testing requires retesting of patients with < 10 mm induration within 2 weeks. If the second skin test results in ≥ 10 mm of induration or the increase in the size of the induration from the first to the second skin test is ≥ 6mm, the patient is considered PPD positive.
The treatment of active MTB in the elderly person is similar to that in young adults. Four-drug therapy (usually isoniazid [INH], rifampin, pyrazinamide, and ethambutol or streptomycin) is recommended as initial therapy, with tapering to one of several two- or three-drug regimens once susceptibility testing is available. The most common regimen is INH, rifampin, and pyrazinamide for 2 months, followed by INH and rifampin for an additional 4 months.
Prophylaxis with 9 months of INH for asymptomatic persons with a positive PPD should be provided regardless of age in adults who are recent converters (defined in persons > 35 years of age with a PPD that has gone from < 10 mm to ≥ 15 mm within 2 years), or regardless of duration of PPD positivity if one is afflicted with any of the specific risk factors highlighted above. Patients with a positive PPD of unknown duration, particularly those over the age of 35 years, should receive INH prophylaxis with close monitoring for symptoms and signs of peripheral neuropathy (due to INH and preventable by coadministration of pyridoxine) and hepatitis (due to INH, rifampin, or pyrazinamide). Shorter course therapy with 2 months of rifampin and pyrazinamide is effective but has a much higher incidence of hepatotoxicity than INH and thus should be used only in very specific circumstances.
Since the early part of the 20th century, infective endocarditis (IE) has undergone a transformation, from a disease of young adults primarily due to rheumatic or congenital valve anomalies to one of older adults associated with degenerative valvular disorders and prosthetic valves. Native-valve endocarditis is typically caused by viridans streptococci, S. aureus, and occasional infections are due to HACEK organisms (a group of typically nonfermenting gram-negative rods that primarily inhabit the oral cavity and include the genuses Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella). Gastrointestinal and genitourinary organisms, such as enterococci and gram-negative rods, are more common in native-valve IE in older adults, and coagulase-negative staphylococci are a common cause of prosthetic-valve endocarditis, particularly in the first 60 days following placement of a prosthetic valve.
The diagnosis of endocarditis is often difficult in the elderly patient. Fever and leukocytosis are less common in elderly than in younger patients, occurring in only 55% and 25%, respectively, versus 80% and 60%, respectively. Blood culture positivity rates do not vary by age; however, degenerative, calcific valvular lesions and prosthetic valves lower the sensitivity of transthoracic echocardiography (TTE) to 45% in older patients (sensitivity is 75% in younger patients). Transesophageal echocardiography (TEE) improves the diagnostic yield for IE, but the absence of positive findings on TEE never excludes IE. TEE is of particular value in resolving the clinical problem of S. aureus bacteremia. Positive findings on TEE support prolonged antibiotic administration (4 to 6 weeks) versus short-course (2-week) therapy. On the other hand, TEE is invasive and expensive. Interestingly, age does not appear to play a major role in mortality risk, with a 2-year survival of 75% for IE in all age groups unless major comorbidities are also present.
Antibiotic treatment of IE is directed at the identified pathogen or the most likely causes, if blood cultures are negative. Therapy is administered intravenously for 2 to 6 weeks. Surgical therapy should be considered for severe valvular dysfunction, recurrent emboli, marked heart failure, myocardial abscess formation, fungal endocarditis, or the failure of appropriate antibiotics to sterilize blood cultures.
Prophylaxis is available for bacterial endocarditis in at-risk patients undergoing dental, upper respiratory tract, gastrointestinal, or genitourinary procedures. Recommendations for endocarditis prophylaxis have been published and are widely available (eg, the American Heart Association, see http://www.amhrt.org).
Permanent implantable prosthetic devices are common in the elderly age group. Prosthetic joints, cardiac pacemakers, artificial heart valves, intraocular lens implants, vascular grafts, penile prostheses, and a variety of other devices are more often placed in older than in younger adults. A discussion of all prosthetic device infections is beyond the scope of this chapter, but several general concepts can be summarized.
Prosthetic device infections are usually separated into early versus late infection because the causative agents differ significantly. Early prosthetic device infection (PDI), most commonly defined as occurring less than 60 days after device implantation, is primarily due to contamination at the time of implantation or events associated with the acute hospitalization (such as occult bacteremias due to intravenous catheters). Thus, coagulase-negative staphylococci predominate, and S. aureus and diphtheroids are common as well; gram-negative bacilli and fungi are relatively rare causes of early PDI. Late PDI is usually caused by organisms that commonly cause transient bacteremia (in the elderly person this is most often skin, respiratory, gastrointestinal, or genitourinary organisms). Staphylococci, including coagulase-negative staphylococci, play a major role in PDIs in both the early and late periods, though their relative importance is greater early. Thus, empiric staphylococcal therapy should be provided in either early or late PDI if a specific causative agent is not identified.
In general, hardware removal is required to clear PDIs. However, early antibiotic intervention, in some instances combined with aggressive surgical drainage, may be successful. Small studies in prosthetic joint infection suggest that initial debridement and culture and a brief course (2 weeks) of intravenous antibiotics followed by combination oral therapy with fluoroquinolones and rifampin for 3 to 6 months may obviate the need for device removal. Until more definitive data are available, it is prudent to restrict this approach to patients with a short duration of symptoms (< 3 weeks), those who are likely to have difficulty tolerating another surgical procedure, or those in whom return to full functional status is not a realistic goal because of comorbidities. In those older adults in whom full functionality is the goal, the best chance for cure is a two-stage procedure in which the device is removed and antibiotics are given for an extended period (6 to 8 weeks), followed by delayed reimplantation. For life-saving devices such as mechanical valves or implantable defibrillators, this is not an option. Infected prosthetic devices are usually surrounded by microbial biofilms, such as microbe-derived glycocalyx. Biofilms reduce antibiotic penetration and greatly increase the bactericidal concentrations of antibiotic without changing the inhibitory concentrations (ie, the amount of drug necessary to inhibit the organism does not change, but it takes tremendously increased concentrations to kill the organism). Furthermore, many conditions associated with infected prostheses are also accompanied by poor blood flow to the area. Thus, it is preferable to use bactericidal antibiotics, often in combination with a second agent that penetrates biofilms and poorly perfused areas (eg, rifampin for staphylococci).
The use of prophylactic antibiotics in situations other than prosthetic heart valves remains a point of contention. Antimicrobial prophylaxis is indicated for dental, gastrointestinal, and genitourinary procedures for patients with prosthetic valves and is probably reasonable for vascular grafts, particularly within the first few months after placement, but no randomized controlled trial has ever clearly shown benefit. The need for prophylaxis for patients with prosthetic joints, intraocular lens implants, cerebrospinal fluid shunts, breast implants, or less common prostheses is even less clear. However, a joint statement by the American Dental Association and American Academy of Orthopaedic Surgeons (AAOS) recommends very limited use of antibiotic prophylaxis in specific patients undergoing dental procedures with a higher bacteremic risk (eg, dental extraction) and who are also at high risk for hematologic seeding (eg, first 2 years after prosthetic joint replacement, immunocompromised or immunosuppressed, or previous prosthetic joint infection). For more information, see the advisory statement posted on the AAOS Web site (http://www.aaos.org/wordhtml/papers/advistmt/1014.htm).
Native bone and joint infections in the absence of prostheses occur in older adults. Septic arthritis is more likely to occur in joints with underlying pathology (rheumatoid changes, gout, osteoarthritis), and early arthrocentesis is indicated in any mono- or oligo-articular syndrome to exclude infection. S. aureus is the most likely pathogen; only rarely are infections due to gram-negative bacilli and streptococci. Aggressive antibiotic therapy combined with serial arthrocentesis may be as effective as open surgical drainage in uncomplicated septic arthritis, and it preserves better functionality in the joint. Surgical drainage is required for patients failing this more conservative strategy.
Osteomyelitis in older adults can be due to hematogenous seeding from a bacteremia or contiguous spread from an adjacent focus. S. aureus is the predominant organism, but gastrointestinal and genitourinary flora are again more common in older adults, which emphasizes the advantage of a specific microbiologic diagnosis to guide therapy. Infections of pressure ulcers and diabetic foot infections are very common, particularly in institutionalized older adults, and they commonly require surgical consultation combined with aggressive antimicrobial therapy aimed at mixed aerobic and anaerobic bacteria.
HIV infection in elderly adults was initially limited to those who had received blood transfusions for surgical procedures. However, increasing numbers of older Americans with HIV have acquired their infection via sexual activity. Older adults constitute approximately 10% of all new diagnoses of acquired immunodeficiency syndrome (AIDS) in the United States, but this group suffers from a lack of HIV awareness among their clinicians. Nonspecific symptoms such as forgetfulness, anorexia, weight loss, and recurrent pneumonia are often dismissed as age-related, and HIV testing can be delayed. Untreated HIV infection in the elderly person tends to pursue a more rapid downhill course, perhaps because of impaired T-cell replacement mechanisms with advanced age and the impact of additional comorbidities. However, if older adults are treated with aggressive highly active antiretroviral therapy (HAART), the response is similar to that seen in young adults. In fact, older adults often are more adherent with complicated HAART regimens than young adults. Treatment regimens and opportunistic infection prophylaxis with the HAART combination are similar to those used in younger persons. Indications that HIV therapies may accelerate atherosclerosis and glucose intolerance suggest that an aggressive approach to cardiovascular prevention in older HIV-infected adults is warranted and may lead to specific recommendations in older adults if associations of metabolic changes with specific HIV therapies become clearer.
HIV prevention is rarely discussed in the geriatric community but is important if the trend of increasing sexual acquisition of HIV in older adults is to be reversed. Most older women do not believe that they are at risk for HIV infection, yet heterosexual activity is the primary mode of infection in this group. The concept of HIV-risky behavior is not pervasive in the geriatric community because HIV was not a problem during their adolescence or young adulthood. Elderly persons must be included in educational programs aimed at ensuring safe sexual practices and increasing awareness of the benefits of testing and effective HIV therapy.
Bacterial meningitis is most common at the extremes of life, and older adults account for the majority of meningitis-associated fatalities. S. pneumoniae remains the most common cause in older adults, but gram-negative bacilli (20% to 25%), Listeria spp. (up to 10%), and tuberculosis are more common than in young adults. Because many S. pneumoniae are now resistant to β-lactam antibiotics (up to 30% penicillin resistance and 10% ceftriaxone resistance nationwide), ceftriaxone or cefotaxime plus vancomycin are recommended as empiric therapy for bacterial meningitis in older adults until a specific isolate can be tested for antimicrobial susceptibility. Ampicillin is the drug of choice for Listeria spp., and more resistant gram-negative rods (eg, Pseudomonas spp.) require ceftazidime or an extended-spectrum penicillin with or without intrathecal aminoglycoside therapy.
Neurosyphilis remains one of the most perplexing diagnoses in medicine. It is often raised as a possible underlying process in stroke or dementia in older adults. Syphilis should also be considered in unilateral deafness, gait disturbances, uveitis, and optic neuritis. In reality, there is no gold-standard test to “rule out” neurosyphilis. Neurosyphilis can only be “ruled in” by such tests. However, suspicion is often first raised when a serum rapid plasma reagent or VDRL is positive. A reasonable diagnostic work-up after discovery of such a positive test includes confirmation of nonspecific tests (rapid plasma reagent and VDRL) with a specific test (microhemagglutination–Treponema pallidum [MHA-TP], or fluorescent treponemal antibody absorption [FTA-ABS]); if tests are confirmed, lumbar puncture should be performed for cell counts, glucose, protein, and cerebrospinal fluid VDRL. A positive cerebrospinal fluid VDRL is diagnostic of neurosyphilis, but the sensitivity of this test is approximately 75% in most series. Other diagnostic tests are controversial. The ratio of intrathecal to serum-specific treponemal antibody (standardized to the total immunoglobulin G in cerebrospinal fluid and serum) may also be helpful, with ratios of 3.0 or greater indicating likely infection. In the absence of these tests, it must be the judgment of a skilled clinician as to whether minor abnormalities in cerebrospinal fluid (eg, low-level pleocytosis) and the clinical picture support the diagnosis and warrant therapy for neurosyphilis. Optimal treatment of neurosyphilis remains penicillin G, but a study in HIV-infected patients suggests that ceftriaxone may be an acceptable alternative.
Advancing age is the major risk factor for reactivated varicella-zoster virus, herpes zoster or “shingles”; the most disabling complication, post-herpetic neuralgia, is common in elderly persons. (See Dermatologic Diseases and Disorders, for diagnosis and treatment.) One study of a zoster vaccine indicates that it can reduce the risk of zoster and post-herpetic neuralgia by > 50%. Recommendations for use of this vaccine in specific age groups are likely to be put forth in the near future.
Facial nerve palsy (Bell’s palsy) is common in older adults and associated with at least three infectious causes: herpes simplex virus, varicella zoster virus, and Borrelia burgdorferi (which causes Lyme disease). There are no strong data, at present, to suggest benefit of antiviral therapy for facial nerve palsies due to herpes simplex virus, but trials are under way. If facial nerve palsy occurs as part of an episode of varicella zoster virus, treatment is indicated (see Dermatologic Diseases and Disorders) If Lyme disease is suspected on a clinical basis, the patient should receive oral amoxicillin, 500 mg four times a day for 14 days; or doxycycline, 100 mg twice a day for 14 days; or intravenous ceftriaxone, 2 g per day for 14 days.
Gastrointestinal infections are common among elderly persons. Diverticulitis, appendicitis, cholecystitis, intra-abdominal abscess, and ischemic bowel can present diagnostic dilemmas in the absence of fever or elevated white blood cell counts. A high index of suspicion is necessary in older adults. Computed tomography or labeled white cell studies are most likely to be of value in establishing the diagnosis of intra-abdominal infection, and ultrasound is an easy, readily available tool to assist in diagnosing cholecystitis, appendicitis, or abscess. Ischemic bowel often requires angiography.
Infectious diarrhea is also common in elderly persons. Older patients with achlorhydria are at particular risk because a lower bacterial inoculum is necessary to cause disease. Decreased intestinal motility associated with specific medications and advanced age may further increase susceptibility to infection. Epidemics occurring in the long-term-care setting are commonly due to E. coli, viruses, salmonellae, or Shigella spp. Frequent use of antimicrobials in older adults also increases the risk for Clostridium difficile colitis. Standard therapies for infectious diarrhea should be used in elderly patients.
Fever of unknown origin (FUO) is currently defined as temperature greater than 38.3°C (101°F) that lasts for at least 3 weeks and is undiagnosed after 1 week of medical evaluation. Several studies have examined this syndrome in elderly patients and demonstrated interesting differences between older and younger adults. The cause of FUO can be determined in more than 90% of cases in elderly persons, and one third have treatable infections, such as intra-abdominal abscess, bacterial endocarditis, tuberculosis, perinephric abscess, or occult osteomyelitis, with an incidence of infection similar to that in younger patients. In contrast, collagen vascular diseases are more common causes of FUO in elderly than in younger patients. These are primarily due to giant cell arteritis, polymyalgia rheumatica, and polyarteritis nodosa, but rarely due to Wegener’s granulomatosis. In several published series, 28% of all FUOs in elderly persons were due to collagen vascular diseases (Table 44.4). Neoplastic disease accounts for another 20%, but, with rare exceptions, fever due to cancer is primarily confined to hematologic malignancies (eg, lymphoma and leukemia), and not solid tumors. Drugs are another cause of FUO in elderly persons. Rare causes in this age group include deep-vein thrombosis with or without recurrent pulmonary emboli and hyperthyroidism.
A diagnostic approach to FUO in older adults is presented in Table 44.5.
■ American Thoracic Society and Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and health-care associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416.
This guideline is a joint recommendation of the American Thoracic Society and Infectious Diseases Society of America. It is a very thorough review of the epidemiology, risk factors, diagnostic testing strategies, and treatment regimens for hospital- (HAP) and health-care-associated pneumonia (HCAP). The important findings suggest initial broad antimicrobial therapy with narrowing to pathogen-directed therapy on the basis of culture data whenever available. One major issue often missed when choosing an initial treatment regimen for HAP or HCAP in older adults is the inclusion of specific coverage for methicillin-resistant Staphylococcus aureus (MRSA) in persons known to be colonized with MRSA.
■ Bentley DW, Bradley S, High K, et al. Practice guideline for evaluation of fever and infection in long-term care facilities. J Am Geriatr Soc. 2001;49(2):210–222.
This comprehensive review of evaluation of fever in residents of long-term-care facilities is an evidence-based compilation of the available literature. The document was approved by the Infectious Diseases Society of America, the American Geriatrics Society, the Gerontological Society of America, and Society for Healthcare Epidemiology of America. It provides guidelines for definition of fever, clinical and laboratory evaluations, criteria for transfer to an acute-care facility, and suggested performance measures for evaluating adequacy of evaluation in long-term-care facilities.
■ Ely EW, Angus DC, Williams MD, et al. Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Inf Dis. 2003;37(2):187–195.
This is an analysis of patients with sepsis aged 75 years or older enrolled in the original randomized trials of activated protein C versus placebo. This is an important analysis because of the increased risk of bleeding in older adults, particularly catastrophic intracerebral bleeding. Older adults were found to have a higher incidence of bleeding than young adults, but the survival benefit of active drug versus placebo at 28 days and prior to discharge remained. The relative risk for death within 28 days was 0.68 (95% confidence interval 0.54 to 0.87) and for in-hospital death for patients treated with drotrecogin alfa was 0.70 (95% confidence interval 0.56 to 0.88).
■ Loeb MB, Becker M, Eady A, et al. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003:51(7):1018–1022.
This evidence-based review comprehensively discusses the available literature on prevention of aspiration in elderly patients. The authors found insufficient data to determine the effectiveness of positioning strategies, modified diets, oral hygiene, or feeding-tube placement for preventing aspiration pneumonia, even though they are widely accepted as effective interventions. Interestingly, only the use of amantadine in nursing-home residents was clearly shown to reduce the risk of aspiration pneumonia and then only in a single trial.
■ Lutters M, Vogt N. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev. 2002;(3):CD001535.
This examined single-dose, short-course (3–6 days) and long-course (7–14 days) therapy for uncomplicated urinary tract infection in older women. It has been widely accepted that 3-day therapy is adequate in young, sexually active adult women, but many practitioners have felt uncomfortable applying these data to older women. The authors conclude that single-dose therapy is less effective, but that there is no difference between short- and long-course therapy. The authors do point out that the quality of the evidence is rather poor and that additional studies would be helpful.
■ Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–2284.
This landmark study in older adults, age 60 years and over, is the first to demonstrate an intervention that reduced the incidence and severity of zoster. This is a live-virus vaccine, based on the varicella vaccine used in children, but with much higher levels of virus. The vaccine reduces zoster by over 60%, and even if zoster occurs, it is less serious with less pain and post-herpetic neuralgia than the illness seen in unvaccinated patients.
■ Perez JL, Moore RD. Greater effect of highly active antiretroviral therapy on survival in people aged ≥ 50 years compared with younger people in an urban observational cohort. Clin Inf Dis. 2003;36(2):212–218.
Untreated human immunodeficiency virus (HIV) infection progresses more rapidly in older adults than in young adults (hazard ratio for death 2.4 for untreated older versus untreated younger adults). Treatment with highly active antiretroviral therapy (HAART) may be difficult in older adults since HAART has been associated with cardiovascular disease, dyslipidemia, osteoporosis, and major health issues in older adults, though a causal relationship has not been established and there are multiple drug-interaction and adherence issues to consider. Data presented in this and other studies suggest that the response and the antiviral and immune-enhancing effects of HAART in adults aged 50 years and older is at least equivalent to that of young adults, and perhaps better. Survival is greatly improved in HAART-treated versus untreated older adults.
■ Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179–186.
This report documents the extensive mortality associated with respiratory viral infection in the United States. Although the association is not new, the data in this study suggest that the magnitude of the association has been grossly underestimated. This is due to the fact that only underlying pneumonia and influenza deaths were previously reported. The new data take into account respiratory and circulatory deaths triggered by a respiratory viral illness. Ninety percent of influenza deaths and 78% of respiratory syncytial virus deaths occurred in persons aged 65 or older.
■ Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004;351(16):1645–1654.
This is an outstanding, comprehensive review of prosthetic joint infection management outlining conservative and aggressive strategies, reporting success rates for each strategy that are based on a thorough literature review, and making antibiotic recommendations for specific pathogens. Importantly, conservation of function, not just cure of infection, are endpoints discussed and emphasized by different strategies.
Kevin Paul High, MD, MSc