A complete review of all the clinical infectious syndromes seen in older adults is beyond the scope of this chapter, and many individual infections are covered elsewhere in this textbook. Common infections not covered elsewhere are reviewed in the following sections.
Although in the middle twentieth century infective endocarditis (IE) was primarily a disease of young and middle-aged adults associated with postrheumatic fever and congenital valvular lesions, it has become a disease of older adults associated with degenerative valvular disorders and prosthetic valves (prosthetic valve endocarditis [PVE]). Furthermore, temporary and permanent pacemakers, pulmonary artery catheters, and other invasive devices are more frequently used in older adults and predispose subjects to IE.
Native valve IE in young adults is typically caused by streptococci, staphylococci, and occasionally by HACEK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella). These same organisms predominate in older adults, but comorbidities and prosthetic devices change the profile of causative agents; gastrointestinal (GI) and genitourinary (GU) organisms such as enterococci and gram-negative rods become more common in native valve IE. Coagulase-negative staphylococci are a frequent cause of PVE, both from contamination at the time of surgery and from occult or documented bacteremia during the hospital stay. Other nosocomial bacteremias, often with more resistant organisms (eg, Enterobacter spp.), can also result in PVE.
Endocarditis is difficult to diagnose in the older adult patient. Fever and leukocytosis are less common (55% and 25%, respectively, for older adults versus 80% and 60%, respectively, for younger patients). As stated above, the prominence of degenerative, calcific valvular lesions and prosthetic valves lowers the sensitivity of TTE. TEE is more sensitive, and improves the diagnostic yield by 45% over that of TTE. Age alone is not a major risk for mortality in IE, with a 2-year survival of 75% for IE in all age groups unless major comorbidities exist—these determine prognosis at any age.
Antibiotic treatment of IE is directed at identified pathogens or the most likely causes if blood cultures are negative (Table 125-1). Therapy is administered intravenously for 2 to 6 weeks. Combination regimens with aminoglycosides are particularly problematic in the older adult patient because of toxicity (both renal and ototoxicity), but is occasionally unavoidable in certain circumstances (eg, enterococcal IE). Surgical therapy is required only when specific criteria are met, primarily recurrent embolic events or worsening heart failure.
TABLE 125-1SUGGESTED EMPIRIC ANTIMICROBIAL THERAPY FOR COMMON INFECTIONS IN OLDER ADULTS |Favorite Table|Download (.pdf) TABLE 125-1 SUGGESTED EMPIRIC ANTIMICROBIAL THERAPY FOR COMMON INFECTIONS IN OLDER ADULTS
|INFECTION ||THERAPY ||COMMENTS |
|Community Acquired |
|Outpatient Therapy |
|Acute sinusitis ||Amoxicillin ||Amox/clav or new macrolide (clarithromycin or azithromycin) if refractory; new macrolide if penicillin allergic |
|Acute exacerbations of chronic bronchitis ||Amoxicillin-clavulanate or resp-FQ ||Infectious exacerbations only; new macrolide if penicillin allergic. Resp-FQs have been shown to extend the time between acute exacerbations and therefore may be preferable in those with frequent, infectious exacerbations |
|Pneumonia ||[Azithromycin or clarithromycin + 2nd gen cephalexin or amox/clav] or resp-FQ ||Review and update immunization status—particularly new recommendation for pneumococcal conjugate vaccine |
|Cellulitis ||Amox/clav or cephalexin ||If pustules/skin abscesses S aureus more likely than Streptococal spp. About half of all S aureus will be community-acquired MRSA; include TMP-SMX or minocycline if suspected. New IV drugs for MRSA (eg, oritivancin, dalbavancin) may change management in near future with single or two-dose IV regimens |
|Infected neuropathic ulcer ||Amox/clav ||Initial outpatient treatment of diabetic foot infection; for penicillin-allergic patient, use cephalosporin if allergy is not severe, use clindamycin + ciprofloxacin for severe allergy |
|Symptomatic UTI ||FQ, TMP-SMX ||Uncomplicated cystitis or pyelonephritis |
|Bacterial diarrhea ||FQ ||Oral rehydration is key—most will resolve without antibiotics. DO NOT USE ANTIBIOTICS IF SHIGA TOXIN IS POSITIVE (due to risk of HUS/TTP) |
|C difficile diarrhea ||Metronidazole or vancomycin ||Use vancomycin if WBC > 15,000 or creatinine > 1.5 times baseline. Fidaxomicin is FDA approved and is equivalent to vancomycin for cure, but reduces relapse rate (cost is a major consideration keeping fidaxomicin from being first-line therapy) |
|Inpatient Therapy |
|Pneumonia ||[Ceftriaxone + azithromycin or clarithromycin] or resp-FQ alone ||Seriously ill (intensive care unit) combination therapy may be best; consider Legionella in seriously ill; consider Pseudomonas if severe COPD (FEV1 < 30% predicted) or structural lung disease |
|Pyelonephritis (no catheter) ||3rd gen cephalosporin or FQ || |
|Sepsis from urologic source (with catheter) ||3rd gen cephalosporin + ampicillin or vancomycin ||Catheter-related sepsis due to urologic source is often polymicrobic; have to consider enterococcal species, in addition to gram-negative bacilli. Early catheter exchange improves outcome |
|Acute bacterial meningitis ||Ceftriaxone + vancomycin ||Vancomycin needed because of small percent of ceftriaxone-resistant S pneumoniae; give dexamethasone with or prior to antibiotics if Gram stain of CSF reveals bacteria. Add ampicillin if Listeria infection suspected (alcoholism, unpasteurized dairy consumption, preceding GI illness) |
|Intra-abdominal infection ||[Ampicillin/sulbactam + gentamicin] or [ampicillin + gentamicin + metronidazole] or pip/tazo or carbepenem ||Surgery nearly always indicated for appendicitis, cholecystitis, ischemic colitis, abscess drainage, but rarely required for diverticulitis; tigecycline for patients with significant β-lacatam allergy |
|Native valve endocarditis ||Penicillin + nafcillin ||Vancomycin for penicillin-allergic patient |
|Prosthetic valve endocarditis || |
Early (< 60 days)—vancomycin + 3rd generation cephalosporin
Late (> 60 days)—vancomycin
|Treat pacemaker and implantable defibrillator devices similarly |
|Infected diabetic foot ulcer ||Ticar/clav or pip/tazo ||3rd gen ceph and clinda for penicillin allergy; tigecycline for significant β-lactam allergy |
|Cellulitis ||Ampicillin/sulbactam ||Add clinda if high suspicion for GAS or vancomycin if MRSA suspected; vancomycin + FQ for β-lactam allergy |
|Septic shock syndrome; with no obvious focus ||Carbepenem; add clindamycin if GAS suspected ||Aggressive supportive care—sepsis bundles/protocols; consider intravenous immunoglobulin if streptococcal toxic shock syndrome |
|Nursing Home Acquired |
|Infected pressure ulcer ||FQ + clindamycin (po); ticar/clav or pip/tazo (IV) ||Pressure-relieving devices, nutrition, debridement essential; culture/x-ray to identify osteomyelitis or MRSA; NEVER do swab culture of surface to identify organism(s)—only surgical cultures of value |
|Pneumonia ||Resp-FQ or ceftriaxone + azithromycin or clarithromycin ||Consider tuberculosis (primary or reactivation); choose empiric coverage of Pseudomonas (eg, change ceftriaxone to cefepime) if heavy antibiotic exposure in last 3 months and/or structural lung disease (eg, COPD with FEV1 < 30% predicted); add vancomycin if MRSA colonized |
|Sepsis due to urinary source ||Ciprofloxcin (po) or ceftriaxone (IM/IV) ||Add enterococcal coverage if catheter present |
|C difficile colitis ||Metronidazole or vancomycin ||See comments above regarding vancomycin vs metronidazole. Close attention to infection control as nosocomial spread documented; spores not killed by alcohol-based antispetics, must wash hands with soap/water |
|Nosocomial/Hospital Acquired |
|Pneumonia ||Cefepime or carbepenem or pip/tazo + vancomycin or linezolid ||Decision influenced by numerous factors: underlying medical conditions, mental status, respiratory support, prior antibiotic exposure, aspiration; risk of MRSA usually elevated in nosocomial pneumonia, thus vancomycin usually justified at initial therapy and can be dropped if no MRSA isolated |
|Catheter-associated urosepsis || |
Vancomycin plus 3rd gen ceph or FQ
|Culture to guide subsequent therapy |
|Intravenous catheter-associated infection (cellulitis, phlebitis, abscess, bacteremia) ||Vancomycin ||If immunocompromised, add cefepime or ceftazidime; surgery required for septic thrombophlebitis |
|C difficle–related diarrhea ||Metronidazole or vancomycin ||See comments above regarding vancomycin vs metronidazole. Discontinue the implicated antimicrobials if possible; attention to infection control and hand washing as noted above |
|Postoperative wound infection; incision/deep with cellulitis, abscess, or bacteremia || |
Cefazolin (mild infection)
Vancomycin + 3rd gen ceph (severe infection)
|Reopen and explore wound; definitive therapy guided by cultures |
Antibiotic prophylaxis is available for bacterial endocarditis for all “at-risk” patients and should be provided for dental, upper respiratory tract, GI, or GU procedures. Although the evidence supporting this practice is relatively weak, it has become the standard of care. Current recommendations for IE prophylaxis are available in sources listed in the references.
Bacteremia rates are much higher in older adults than in younger patients, comprising up to 14% of all admissions in some geriatric units. Older patients with bacteremia are less likely than younger patients to have systemic signs such as fever, chills, or diaphoresis. Bacteremia in older adults is more likely to arise from a gastrointestinal or genitourinary source than in young adults. Thus, the causative agent is more likely to be a gram-negative rod.
Despite a similar initial cytokine response to that of young adults with sepsis, the prognosis of sepsis in older adults is worse. The 28-day mortality for sepsis in young adults is 26% to 33% versus 35% to 42% in adults older than age 65 years. Nosocomial gram-negative bacteremia carries a mortality rate of 5% to 35% in young adults, but 37% to 50% in older adults. A major contributing factor is reduced physiologic reserve because of age and comorbidities that reduce the ability of older adults to recover from a septic episode.
Antibiotic management of bacteremia and sepsis in older adults is similar to that of younger adults, and the importance of initially broad coverage must be emphasized. Mortality is greatly reduced if an antibiotic that covers the eventually isolated organism is included in the initial regimen, whereas waiting to identify the organism and switching the antibiotic once identified has little to no effect on overall survival. Thus it is imperative to include coverage for MRSA, resistant gram negative rods, enterococci and other resistant organisms when there is a high clinical suspicion for resistant organisms in an older adult, in particular nursing home residents represent a high-risk population.
Prosthetic Device Infections
As the prevalence of the US population older than age 65 years has increased, permanent implantable prosthetic devices have become quite common. Prosthetic joints, cardiac pacemakers, artificial heart valves, intraocular lens implants, vascular grafts, penile prostheses, and a variety of other devices are primarily placed in older adults. Foreign bodies provide a conducive environment for bacterial colonization and inhibit host immune factors, often leading to infection. While it is impossible to review all prosthetic device infections in this chapter, several general concepts can be stated. Prosthetic device infections are usually categorized by causative agents that typically present early (< 60 days from implantation) or late (> 60 days). Early infections are primarily caused by contamination at the time of surgery or events associated with the implantation hospitalization (eg, bacteremia caused by IV or urinary catheters). Thus, the causative organisms for early prosthetic device infections are primarily skin and nosocomial flora. Coagulase-negative staphylococci predominate; S aureus and diphtheroids are common as well. Gram-negative bacilli, fungi, or polymicrobial infections are rare causes of early infection except when the material itself or associated products such as dressing material are contaminated. Late infections tend to be caused by the same organisms that cause community-acquired bacteremia in the older adult population, and bacteremic seeding of the device is likely the mode of infection in these cases. Staphylococci, including coagulase-negative staphylococci, are the exception to this rule, playing a major role in prosthetic device infections in both the early and late periods. Thus, empiric antistaphylococcal therapy is imperative in either early or late prosthetic device infection.
It is difficult to cure prosthetic device infections (ie, eradicate the organism) with the device in place. However, in some instances, early antibiotic intervention combined with aggressive surgical debridement may result in cure without removing the device. Because prosthetic device infections often include biofilms and occur in the setting of other factors that limit antibiotic efficacy (eg, poor circulation), it is preferable to use bactericidal antibiotics, and combinations with a second agent that penetrate these areas well (eg, rifampin) may be most effective when trying to cure infection with a device remaining in place. If early, aggressive therapy is ineffective in controlling the infection, it is imperative that the device be removed. In prosthetic joint infection (the clinical entity of device-related infection most well-studied) two-stage procedures, where the device is removed and antibiotics given for an extended period (usually 6 weeks) with delayed reimplantation have the highest success rate. However, for life-saving devices, such as mechanical valves or implantable defibrillators, this is not an option.
Prevention of prosthetic device infection is facilitated by the use of clean air systems and/or personal isolator systems in the operating room. Although there are limited data for efficacy, typical antimicrobial prophylaxis for clean surgery is appropriate; prophylaxis other than at the time of surgery remains unproven. However, perioperative antimicrobial prophylaxis for dental, GI, and GU procedures is indicated for prosthetic valves and is frequently employed for vascular grafts, particularly within the first few months after placement. There is no evidence to demonstrate benefit for prophylaxis in patients with prosthetic joints, intraocular lens implants, intracoronary artery stents, cerebrospinal fluid shunts, breast implants, or other less-commonly used prostheses. The American Dental Association (ADA) recommends “considering” antibiotic prophylaxis for patients with prosthetic joint at “high risk,” which the ADA define as joints within 2 years of placement, immunosuppressed patients (including immune compromise as a result of diabetes mellitus, rheumatoid arthritis, and malnourishment), or those with a previous joint infection.
It has long been established that advanced age is a major risk factor for developing tuberculosis (TB), and even with the increasing populations of young adults at risk due to the HIV epidemic and increasing immigrant populations, older adults still comprise approximately one-fourth of all TB cases reported in the United States. Tuberculosis often presents differently in older adults than in young adults. Several studies have demonstrated that, when compared to young adults, older adults are less likely to present with fever, night sweats, cough, or hemoptysis, and more likely to present with nonspecific symptoms of dizziness, nonspecific pain or mental “dullness,” a prior history of tuberculosis, and a concomitant diagnosis of underlying cancer. Radiographic and laboratory differences also occur with older adults being more likely to have widespread pulmonary parenchymal infiltrates whereas young adults are more likely to have isolated upper lobe infiltrates, and older adults are more likely to have evidence of malnutrition (ie, reduced serum albumin).
The most important issue of TB management in older adults remains the challenge of diagnostic testing. Using the tuberculin skin test (TST) in classic studies, William Stead and colleagues at the University of Arkansas defined the prevalence of TST positivity in older adult residents of long-term care facilities, the risk for reactivation of M tuberculosis with and without prophylactic therapy, and the survival of older adults in each of these situations. Overall conclusions from these studies suggest that the sensitivity of the TST to detect latent infection declines with age, that TB is rare (< 0.2%) in older residents in whom the TST is never positive, that TST positive individuals develop clinical disease 2% to 5% of the time (this is increased two- to threefold if the TST represents a recent conversion), and that isoniazid (INH) prophylaxis in TST positive subjects reduces the risk of clinical disease to < 0.3% for most subjects (the exception being those who are TST positive and previously had active tuberculosis—in those cases, isoniazid therapy reduced the risk from 2–5% to 1.5–2%). The benefits of isoniazid prophylaxis are long-lasting with improved survival in TST-positive treated subjects (vs untreated TST positive subjects) apparent at 1.5 years and persisting up to at least 8 years.
From these data it is clear that identifying TST positive older adults is important for preventing active tuberculosis through INH prophylactic treatment. Confounding issues, however, surround interpretation of the TST. In the most recent guidelines from the American Lung Association, a TST is considered positive if greater than 5 mm induration in HIV-positive persons, recent TB contacts, those with fibrotic changes on chest radiograph consistent with prior TB, and immunosuppressed patients (including those on ≥ 15 mg/day of prednisone for at least 1 month); greater than 10 mm is considered positive for recent immigrants, injection drug users, residents and employees of healthcare facilities (including nursing homes), and persons with high-risk conditions (silicosis, diabetes mellitus, chronic renal failure, leukemia/lymphoma, head and neck or lung cancer, weight loss ≥ 10% of ideal body weight, and status post gastrectomy); for all other persons, a TST greater than 15 mm is considered positive.
Equally as important to appropriate interpretation is the need to do “two-step” initial testing in those who will undergo serial testing (such as residents of long-term care and health care workers). Some people infected with M tuberculosis may have a negative reaction to initial testing if many years have passed since they became infected. This false positive skin test may be revealed by a positive reaction to a subsequent TST that is “boosted” by the first test. If this is not recognized at the time of initial testing, a subsequent positive may incorrectly be interpreted as a skin test conversion (going from negative to positive). For this reason, the “two-step method” is recommended (Figure 125-3) in those who will undergo periodic testing thereafter (eg, nursing home residents, health care workers).
Interpretation of “two-step” tuberculin skin testing (TST) in nursing home residents and others (eg, healthcare workers) who will undergo repeat TST. LTBI, latent tuberculosis infection; TB, tuberculosis. (Reproduced from Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Centers for Disease Control and Prevention.)
New diagnostic tests for tuberculosis have been developed and include quantitation of interferon-γ release assay (IFGA) from whole blood measured after ex vivo M tuberculosis antigen stimulation. Unfortunately, these newer assays have only demonstrated modestly improved sensitivity or specificity and not in older adults. The pooled sensitivity from multiple studies appears to be 71% for TST versus 76% for IFGA. The specificity for the three tests is 66% and 97%, respectively. None of the tests appears to be useful for the following response to therapy with the specificity increase for the IFGA being most useful in those who have received Bacillus Calmette–Guérin (BCG) immunization.
The treatment of tuberculosis in older adults does not differ from that of young adults, but older adults are more susceptible to adverse effects and drug-durg interactions. Latent disease (TST positive only without clinical signs and symptoms), if not previously treated, should be treated with 9 to 12 months of INH, whereas patients with clinical illness should initially receive four drugs (usually INH, rifampin, pyrazinamide, and ethambutol), pending culture and susceptibility testing. The duration of therapy depends on many factors including the site of infection, susceptibility test results, and clinical response.
Fever of unknown origin (FUO), classically defined as temperature more than 101°F (38.3°C) for at least 3 weeks and undiagnosed after 1 week of medical evaluation, has different causes in older adults than in young adults (Table 125-2), and these differences influence the diagnostic work-up. The cause of FUO can be determined in virtually all cases and approximately one-third of cases will have treatable infections (eg, intra-abdominal abscess, bacterial endocarditis, tuberculosis, or occult osteomyelitis). In contrast to young adults, connective-tissue disease (CTD) is a more frequent cause of FUO in adults older than age 60 years. A compilation of several recently published series suggests that 25% of all FUOs in the older adult patient are caused by CTDs. However, the CTD most likely to cause FUO in young adults, systemic lupus erythematosus (SLE), is absent in series of older adults and replaced by temporal arteritis (TA) and polyarteritis nodosa (PAN). Neoplastic disease accounts for another 20%, most often a result of hematopoietic malignancies (eg, lymphoma and leukemia). Importantly, however, multiple myeloma, a disease much more likely in older adults than in young adults, is almost never a cause of FUO. Drug fever is a common cause of FUO in older adults, and granulomatous angiitis, deep venous thrombosis with or without recurrent pulmonary emboli, and hyperthyroidism occasionally cause FUO in older adults.
TABLE 125-2FEVER OF UNKNOWN ORIGIN (FUO) IN THE OLDER PATIENTS |Favorite Table|Download (.pdf) TABLE 125-2 FEVER OF UNKNOWN ORIGIN (FUO) IN THE OLDER PATIENTS
|MAJOR CAUSES ||% OF CASESA |
|Infections ||35 |
| Intra-abdominal abscess ||12 |
| Tuberculosis ||6 |
| Infective endocarditis ||10 |
| Other ||7 |
|Collagen vascular disorders ||28 |
| Temporal arteritis/polymyalgia rheumatica ||19 |
| Polyarteritis nodosa ||6 |
| Other ||3 |
|Malignancy ||19 |
| Lymphoma/other hematologic ||10 |
| Solid tumors ||9 |
|Other (pulmonary emboli, drug fever) ||10 |
|No diagnosis ||8 |
A reasonable approach to FUO in older adults can be inferred from the most likely causative entities. A thorough history and physical examination; basic laboratory evaluations of complete blood counts with differential, serum chemistries and hepatic enzymes, thyroid function studies, erythrocyte sedimentation rate (ESR), placement of a purified protein derivative (PPD) skin test, a chest x-ray, and initial blood and urine cultures should begin the search. If the diagnosis continues to be elusive and the ESR is elevated, temporal artery biopsy even in the absence of typical history or objective physical findings should be strongly considered. If the source remains obscure, or if there is a low suspicion for temporal arteritis, abdominal imaging with computed tomography (CT) or magnetic resonance imaging (MRI) should be performed. Further invasive diagnostic procedures, such as bone marrow and liver biopsy, or laparoscopy, should be considered in specific cases, but are low yield unless there are significant clues for involvement (eg, cytopenias or hepatomegaly).