Infective Endocarditis in Elderly Patients

Transcription

1 AGING AND INFECTIOUS DISEASES Thomas T. Yoshikawa, Section Editor INVITED ARTICLE Infective Endocarditis in Elderly Patients Vinod K. Dhawan Charles R. Drew University of Medicine and Science, Martin Luther King, Jr. Charles R. Drew Medical Center, and University of California Los Angeles School of Medicine, Los Angeles Infective endocarditis (IE) in elderly patients presents a unique diagnostic and therapeutic challenge. Atypical presentations frequently lead to delayed diagnosis and poor outcome. IE in elderly persons is somewhat more common among men. Underlying degenerative valvular disease, mitral valve prolapse, and the presence of a prosthetic valve are important risk factors predisposing elderly persons to IE. Streptococci and staphylococci are the predominant organisms, which are recovered from 80% of elderly patients with IE. In older patients, IE occurs somewhat more frequently on the mitral valve than it does on the aortic valve. The presence of calcific valvular lesions and the prosthetic valves often confound the echocardiographic findings in elderly patients. A high index of suspicion and an aggressive diagnostic approach are required to ensure timely diagnosis and appropriate therapy. An important aspect of evolving epidemiology of infective endocarditis (IE) has been an upswing in the average age of patients with this disease. Whereas the mean age of patients with IE was 35 years in the early 1940s, with only 10% of cases reported in patients aged 160 years, a more recent series reported a mean age of 55 years, with 50% of cases occurring in patients aged 160 years [1]. The increased incidence of IE among elderly patients can be attributed to several factors. (1) A decreased incidence of rheumatic heart disease (a risk factor for IE) has been observed with the advent of effective antistreptococcal therapy. Because rheumatic heart disease predominantly affects younger people, the frequency of IE in this age group has decreased proportionately. (2) Life spans of patients with rheumatic and congenital heart diseases are increasing as a result of advances in the field of cardiothoracic surgery, which has increased the number of older persons in the pool of atrisk patients. (3) The incidence of calcific/degenerative heart disease (typically seen in old age) and its related IE has increased commensurately with increased life expectancy. (4) Newer invasive therapeutic interventions (particularly use of intravenous catheters, pacemakers, and dialysis shunts), which elderly per- Received 5 September 2001; revised 20 November 2001; electronically published 31 January Reprints or correspondence: Dr. Vinod K. Dhawan, Div. of Infectious Diseases, Dept. of Internal Medicine, King Drew Medical Center, S. Wilmington Ave., Los Angeles, CA (vidhawan@cdrewu.edu). Clinical Infectious Diseases 2002; 34: by the Infectious Diseases Society of America. All rights reserved /2002/ $03.00 sons are more likely to receive, have all increased the risk of bacteremia and subsequent IE in the elderly population. (5) More frequent prosthetic cardiac valve placement in recent years has added a unique category of patients at risk for IE, a larger proportion of which are elderly. The diagnosis and treatment of IE in elderly patients are particularly challenging; a high index of suspicion is required, as is careful monitoring for complications. This review highlights the unique aspects of IE in elderly patients. EPIDEMIOLOGIC FEATURES In the elderly population, IE is somewhat more common in men. The ratio of men to women is 1.2:1 to 3:1 in adults with IE, but it is 2 8:1 in patients aged 160 years [2]. IE in older patients occurs somewhat more frequently on the mitral valve. In a recent series of 44 elderly patients who had endocarditis diagnosed by use of the Duke criteria, the mitral valve was affected in 20 patients (45%), the aortic valve was affected in 14 patients (32%), and both the mitral and aortic valves were involved in 2 patients (5%) [3]. Similarly, a retrospective review of endocarditis that was diagnosed by use of the Duke criteria noted mitral valve involvement in 52% of elderly patients, whereas the aortic valve was the site of involvement in 55% of younger patients [4]. Degenerative valvular heart disease is being increasingly associated with endocarditis in the elderly population. The normal aortic valve frequently undergoes degenerative calcification with 806 CID 2002:34 (15 March) AGING AND INFECTIOUS DISEASES

2 advancing age (figure 1). Such a valve is functionally stenotic as a result of the restricted mobility of its cusps. The resulting turbulence predisposes elderly patients to IE. Similarly, the natural history of congenital bicuspid aortic valve is of calcification, which occurs in nearly all persons aged 140 years. Autopsy findings have revealed calcification of congenitally bicuspid valve to be the most common cause of aortic stenosis in patients aged years [5]. The presence of a bicuspid aortic valve may predispose elderly patients to IE, although endocarditis on such valves tends to occur at a younger age. A study of 50 patients with bicuspid aortic valve IE noted that the mean age of such patients was 39 years [6]. Likewise, progressive calcification of mitral annulus occurs with advancing age: it occurs in 3.2% of women aged!70 years but in 44% of women aged 190 years [7]. Men are one-half as likely as women to have mitral annular calcification [7]. Patients with mitral valve prolapse and mitral regurgitation are more susceptible to IE, a risk particularly pronounced in men aged 145 years. The predominant organisms in IE, which are responsible for 80% cases in the elderly population, are streptococci and staphylococci. Some studies have noted a higher prevalence of enterococci among elderly patients with IE [8]. Also, Streptococcus bovis, an organism associated with colonic malignancy, may be noted more commonly in elderly patients with IE [9]. The HACEK group of organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) occasionally may be responsible. Intravascular catheters and urinary catheters placed in elderly individuals may be a source of bacteremia and IE. Elderly diabetic patients have increased staphylococcal colonization of their skin and nares with proportionate increase in the risk of bacteremia and complicating IE [2]. Antibioticresistant organisms (e.g., methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-resistant pneumococci) are more prevalent in nursing homes and are conceivably more likely to be noted as the source of infections in elderly persons [10]. However, a recent study of elderly patients with endocarditis did not notice any significant difference in the prevalence of various pathogens as compared with younger patients [3]. The increasing use of bioprosthetic valves and the increasing number of older persons who survive previous episodes of IE are important additional risk factors. The average incidence of prosthetic valve endocarditis is 1% 4% in the first year after surgery and 1% yearly thereafter. Significant risk of IE with advancing age is reflected by the incidence-rate ratio of 8.8:1 for persons aged 65 years, as compared with persons aged!65 years [11]. The frequency of at-risk conditions in the elderly heart were documented by a study in which 42% of nursing home patients aged 160 had some underlying cardiac abnormality predisposing them to IE [11]. CLINICAL ASPECTS The clinical presentation of IE in elderly individuals may be nonspecific. Several articles have emphasized that atypical presentations of IE are quite common among elderly patients and that diagnosis is frequently delayed [12 18]. The presenting manifestations of IE in the older patients are constitutional symptoms, such as lethargy, fatigue, malaise, anorexia, and Figure 1. Transthoracic echocardiogram showing aortic valve calcification in an 82-year-old patient AGING AND INFECTIOUS DISEASES CID 2002:34 (15 March) 807

3 weight loss, all of which can be attributed to aging and other disorders that are more likely to occur among elderly persons. The febrile response is often blunted in older patients. Some elderly patients manifest worsening of congestive heart failure. New cardiac murmurs (caused by progressive valvular damage and valvular incompetence) are highly indicative of IE. However, approximately one-third of patients with tricuspid valve disease and patients who have only mural involvement may not have a pathologic murmur on initial presentation. In addition, heart murmurs in elderly individuals may be erroneously attributed to the underlying valvular calcification and, therefore, neglected. Alternatively, IE in elderly persons may present with a stroke syndrome, rheumatologic complaints, or peripheral nervous system abnormalities [12, 19]. Musculoskeletal manifestations of IE include backache, arthralgia, septic arthritis, and osteomyelitis. In 1994, Durack et al. [20] refined the existing clinical criteria for diagnosis of IE through incorporation of echocardiographic findings. Further modifications of the Duke criteria have been proposed more recently in an effort to improve the accuracy of clinical diagnosis of IE (table 1) [21]. Studies that used the Duke criteria for diagnosis of IE have found no relevant differences between elderly patients and their younger counterparts with regard to the frequency of fever, heart failure, embolic events, neurologic symptoms, distribution of causative organisms, and cerebral deficit at the time of discharge from the hospital [3, 4]. However, renal insufficiency at admission and malignancy are significantly more common among elderly patients with IE [3, 4]. The unique features of IE in elderly individuals are listed in table 2. DIAGNOSIS The hallmark of IE is continuous and high-grade bacteremia due to intravascular infection. The putative organism can be recovered in 98% of patients by obtaining 3 sets of blood samples for culture. Previous antibiotic therapy may lower this yield. Leukocytosis with left shift is common; leukopenia and thrombocytopenia are noted rarely [22]. Anemia may be present in patients with subacute disease. The erythrocyte sedimentation rate is elevated in elderly patients, except for those with congestive heart failure. Microscopic hematuria, proteinuria, RBC casts, and bacteriuria may be noted by means of microscopic evaluation of urine specimens. Rheumatoid factor may be present, complement levels may decrease, and immune complexes may be noted. Chest radiographs of patients with right-sided IE may reveal multiple round densities, cavitary multilobar infiltrates, and pleural effusions due to septic emboli. Electrocardiography may reveal conduction defects secondary to interventricular septal abscess formation [23]. CT scanning of the head of patients who manifest CNS abnormalities may reveal macroscopic abscess and diffuse cerebritis that are caused by IE due to highly virulent organisms in 0.5% and 0.9% 3.8% of patients, respectively [19, 22]. Arteriography is useful in outlining the mycotic aneurysms. Echocardiography has revolutionized the diagnosis of heart diseases, including IE. Elderly patients are more likely to have predisposing valvular conditions (e.g., degenerative and calcific lesions; figure 1) and prosthetic valves, which decrease the sensitivity of transthoracic echocardiography to 45% [8]. Its sensitivity is also decreased in elderly patients in the presence of obesity, chest wall deformities, and chronic obstructive pulmonary disease [24]. Transesophageal echocardiography (TEE), a newer technique, has increased the diagnostic yield of IE in the elderly patients by 45% [8]. TEE, with its overall sensitivity of 90%, is also superior to transthoracic echocardiography in detecting smaller vegetations (diameter, 5 mm), diagnosing valvular perforation, demonstrating valvular regurgitation, and delineating aneurysm and periannular abscess formation [23]. TREATMENT Prompt intravenous administration of bactericidal antibiotics is critical in the management of IE. After appropriate samples are obtained and cultured, antibiotic therapy should be initiated empirically. In the typical patient with a subacute presentation, therapy of IE should be directed at streptococci with a combination of ampicillin (or penicillin) and an aminoglycoside (e.g., gentamicin). In cases with acute onset in which staphylococci are considered to be the more likely pathogens, therapy may be initiated with semisynthetic penicillin, such as nafcillin (or vancomycin, in patients with a penicillin allergy or in the presence of suspected methicillin resistance), along with an aminoglycoside (e.g., gentamicin). For patients with prosthetic valve endocarditis, treatment should be initiated empirically with vancomycin and gentamicin, with or without rifampin. The therapy is later adjusted on the basis of the pathogen identified. If penicillin-susceptible streptococci (MIC, 0.1 mg/ml) are implicated, treatment of IE may be continued for a period of 4 weeks with aqueous penicillin G (10 20 million U q.d. given iv at 6 h intervals) or ceftriaxone (2 g given iv q.d.), or, for elderly persons who have a serious allergy to penicillin, with vancomycin (dose adjusted for creatinine clearance). A randomized, multicenter, open-label study reported that a 2-week regimen of ceftriaxone (2 g q.d.) in combination with gentamicin (3 mg/kg q.d.) was as effective as a 4-week regimen of ceftriaxone (2 g q.d.) [25]. The combination therapy group included 25 patients with an age range of years ( mean SD, years). Adverse effects were minimal in both groups. Treatment of IE due to enterococci or other 808 CID 2002:34 (15 March) AGING AND INFECTIOUS DISEASES

4 Table 1. Modified Duke criteria for diagnosis of infective endocarditis (IE). Definite endocarditis Histologic and/or microbiologic evidence of infection at surgery or autopsy 2 major criteria 1 major criterion and 3 minor criteria 5 minor criteria Possible endocarditis 1 major criterion and 1 minor criterion 3 minor criteria No endocarditis Negative findings at surgery or autopsy for a patient who received antibiotic therapy for 4 days Firm alternative diagnosis Resolution of illness with antibiotic therapy for 4 days Failure to meet criteria for possible endocarditis Major criteria Blood cultures positive for IE Typical microorganism consistent with IE isolated from 2 separate blood cultures, as noted below Viridans streptococci, Streptococcus bovis, Staphylococcus aureus, or HACEK group Community-acquired enterococci in the absence of a primary focus Microorganisms consistent with IE isolated from persistently positive blood cultures defined as: At least 2 positive cultures of blood samples obtained 112 h apart All of 3 or a majority of 4 or more separate cultures of blood, the first and the last sample obtained 11 h apart Single blood culture positive for Coxiella burnetii or an antiphase I IgG antibody titer of 11:800 Evidence of endocardial involvement Positive results of echocardiography for IE (transesophageal echocardiogram recommended for prosthetic valve, possible IE by clinical criteria, or complicated IE [i.e., a paravalvular abscess]) defined as: Oscillating intracardiac mass on the valve or supporting structures in the path of regurgitant jets or on implanted material in the absence of an alternative anatomic explanation Abscess New partial dehiscence of a valvular prosthesis New valvular regurgitation (worsening or changing or preexisting murmur not sufficient) Minor criteria Predisposing heart disease or injection drug use Temperature of 138 C Vascular phenomenon: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial or conjunctival hemorrhage, Janeway s lesions Immunologic phenomenon: glomerulonephritis, Osler s nodes, Roth s spots, rheumatoid factor Microbiologic evidence: a positive blood culture that does not meet a major criterion (as noted above) or serologic evidence of active infection with an organism consistent with IE NOTE. Adapted from [20] and [21]. HACEK, Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacteriumhominis, Eikenella corrodens, and Kingella kingae. penicillin-resistant streptococci (MIC, 1.0 mg/ml) requires a combination of aqueous penicillin G (20 million U q.d. given iv at 6 h intervals) or ampicillin (2 g given iv every 4 h) with gentamicin (1 mg/kg q8h). Therapy is continued for 4 6 weeks. Vancomycin is substituted for penicillin or ampicillin for elderly patients who are allergic to b-lactams. Endocarditis due to methicillin-susceptible staphylococci can be treated with penicillinase-resistant penicillin (nafcillin or oxacillin, 2 g given iv every 4 h) or a cephalosporin (cephalothin, 2 g given iv every 4 h, or cefazolin, 1 2 g given iv or im q8h). The usual duration of therapy for IE is 4 6 weeks. An aminoglycoside, such as gentamicin, may be added during the first 5 days of therapy to achieve rapid clearance of bacteremia and a possible rapid decrease in the number of bacteria in vegetations while avoiding potential aminoglycoside nephrotoxicity [22]. Experience with once-daily dosing of aminoglycoside therapy for staphylococcal IE is limited. Uncomplicated right-sided IE caused by a drug-susceptible strain of AGING AND INFECTIOUS DISEASES CID 2002:34 (15 March) 809

5 Table 2. Unique features of infective endocarditis (IE) in elderly patients. Feature Presentation Microbiology Underlying disease Valvular involvement Sex distribution Echocardiography Diagnosis Prognosis Comments Elderly patients frequently have blunted febrile responses. Cardiac auscultation is often confounded by a high frequency of preexisting murmurs from degenerative valvular disease. Alternatively, endocarditisinduced murmurs may not be easily appreciated on initial presentation as a result of emphysema and narrow intercostal spaces. Streptococci and staphylococci are the predominant organisms; they are recovered in 80% of cases of IE. Enterococci are somewhat more prevalent in the elderly population with IE. Streptococcus bovis may cause IE in association with colonic lesions. Degenerative valvular disease, mitral valve prolapse, and the presence of a prosthetic valve are important risk factors predisposing elderly individuals to IE IE in older patients is somewhat more common on the mitral valve than it is on the aortic valve Endocarditis in the elderly population is somewhat more common in men Presence of calcific valvular lesions and prosthetic valves make the echocardiographic findings difficult to interpret. Use of transesophageal echocardiography has improved the diagnostic yield for these patients. Frequently delayed because of atypical presentations and difficulty in interpreting echocardiographic findings Generally poor as compared with nonelderly persons. It is largely the result of delayed diagnosis and therapy. Staphylococcus aureus can usually be cured with a 2-week combination of semisynthetic penicillin (e.g., nafcillin) and an aminoglycoside [26]. However, this abbreviated treatment has not been studied in the elderly population and should be avoided because of the potential for aminoglycoside toxicity. Careful attention to renal function and aminoglycoside serum concentration is particularly important in older patients to minimize nephrotoxicity. When synergy with another agent is demonstrated, serum levels of aminoglycoside that are lower than levels generally considered therapeutic may be adequate. Vancomycin is less rapidly bactericidal than is nafcillin in vitro against S. aureus, especially at high inocula, resulting in rates of clinical failure of 40% [27]. Vancomycin therapy should be reserved for management of staphylococcal endocarditis in the presence of methicillin resistance or severe penicillin allergy. Because of impaired renal clearance in elderly persons, the vancomycin dosage should be adjusted accordingly. Most elderly patients achieve therapeutic levels with a vancomycin dose administered once per day. Serum concentration of vancomycin should be obtained for optimal dosing. The role of newer antimicrobial agents, such as quinupristin-dalfopristin and linezolid, in the treatment of IE due to antibiotic resistant grampositive cocci in elderly patients has not been established. Elderly patients with IE due to the HACEK group of organisms may be treated with ceftriaxone (2 g given iv q.d.) for 4 weeks. In patients with uncomplicated IE, defervescence occurs within a week of effective therapy. Persistent fever suggests a septic embolic focus (kidney, spleen, or liver), inadequate therapy, drug hypersensitivity, immune complex tissue injury, and valve ring abscess. Antibiotic therapy decreases the risk of first and recurrent embolization. With effective therapy, the risk of embolization decreases from 17 events per 100 patient-days in the first week to!5 events per 100 patient-days during the second and third weeks [28]. In general, elderly patients with IE generally have longer durations of hospitalization than do younger patients with IE (mean duration, 42 days vs. 32 days in one study) [3]. As a result of improved surgical techniques and the availability of longer-lasting prosthetic valves, patients with IE have undergone operations with acceptable rates of morbidity and mortality. The actuarial survival rate at 5 years after valve replacement for endocarditis is 47% 71% [29]. Accepted indications for surgery in the setting of IE include the following: (1) failure of medical management and continuing bacteremia, unrelated to a metastatic abscess formation (a patient who experiences this is likely to have valve ring abscess); (2) acute left-side heart failure that is unresponsive to medical therapy; (3) 11 serious systemic embolic episode; (4) endocarditis due to organisms for which curative antimicrobial therapy is not available (e.g., fungi, rickettsiae, vancomycin-resistant enterococci); (5) a ruptured sinus of Valsalva mycotic aneurysm; (6) a myocardial abscess, as suggested by new conduction abnormalities or by echocardiography; (7) a large (diameter, 11 cm) anterior mitral leaflet vegetation; and (8) prosthetic valve endocarditis caused by nonstreptococcal organisms [30, 31]. Although valve replacement is necessary for left-side IE, tricuspid valvulectomy or vegetectomy with valvuloplasty may be adequate for tricuspid valve disease. Elderly patients are at greater risk of postoperative complications, including prosthetic dysfunction, pericardial tamponade, renal insufficiency, rhythm disturbances, and the necessity for a second intervention [4]. PROGNOSIS Advanced age has been associated with poor prognosis. An agedependent increase in mortality rates up to 32% has been reported in patients aged 160 years [32]. This may be largely because atypical presentations of IE in elderly patients result 810 CID 2002:34 (15 March) AGING AND INFECTIOUS DISEASES

6 in delayed recognition and therapy. Recent studies have noted that age itself is not an independent predictor of adverse outcome [4, 33]. Unfavorable prognostic factors include the presence of neurologic sequelae, acute myocardial infarction, and infection with S. aureus and fungi. PREVENTION Elderly patients undergo a large number of diagnostic and therapeutic procedures. Many of these procedures carry substantial risks of bacteremia with potential seeding of susceptible cardiac valves. Chemoprophylaxis should be considered for all elderly patients at risk for IE undergoing dental manipulations; instrumentation involving the respiratory, genitourinary, or gastrointestinal tract; and surgical procedures likely to cause bacteremia. For effective prophylaxis, it is necessary to achieve bactericidal levels of an antibiotic before a bacteremic episode. The American Heart Association has recently updated recommendations for prophylaxis of IE [34]. There has been shift toward use of prophylaxis in fewer high-risk dental, genitourinary, or gastrointestinal tract procedures; fewer selected high-risk cardiac lesions; and a single-dose prophylaxis. For dental, oral, respiratory, or esophageal procedures, antibiotic prophylaxis directed at viridans streptococci may be provided with amoxicillin (2 g given orally) 1 h before procedure or ampicillin (2 g given iv or im) 30 min before the procedure. Alternative orally administered regimens for patients who are allergic to penicillin that are given as a single dose 1 h before procedure include clindamycin (600 mg), cephalexin-cefadroxie (2 g), azithromycin (500 mg), and clarithromycin (500 mg). Parenteral alternatives for penicillin-allergic patients include clindamycin (600 mg given iv ) or cefazolin (1 g given im or iv) administered 30 min before the procedure. Prophylactic regimens for genitourinary and gastrointestinal (except esophageal) procedures target enterococci and take into account the risk of IE relative to the underlying cardiac conditions. Patients with high-risk conditions (prosthetic heart valve, previous endocarditis, complex cyanotic congenital heart disease, and surgically constructed systemic-pulmonary shunts) should receive ampicillin (2 g given iv or im) plus gentamicin (1.5 mg/kg given iv) 30 min before procedure, followed by a dose of ampicillin (1 g given im or iv) or amoxicillin (1 g given orally) 6 h later. Alternatively, vancomycin (1 g given iv in a 1 2 h infusion completed 30 min before procedure) plus gentamicin (1.5 mg/kg given iv) may be used 30 min before the procedure. There is a moderate risk of IE posed by other underlying cardiac diseases, such as unrepaired congenital cardiac malformations (except isolated secundum atrial septal defect), most acquired valve dysfunctions, hypertrophic cardiomyopathy, and mitral valve prolapse with regurgitation (and/or thickened leaflets). Patients with such conditions can receive IE prophylaxis with amoxicillin (2 g given orally) 1 h before the procedure, ampicillin (2 g given im or iv) 30 min before the procedure, or vancomycin (1 g given iv) provided in a 1 2 h infusion completed 30 min before the procedure. Several aspects of IE in the elderly population require further investigation. More precise diagnostic strategies need to be evaluated. The sensitivity and specificity of TEE for the diagnosis of IE in elderly individuals should be further delineated. The role of newer antimicrobials, such as quinupristin-dalfopristin and linezolid, in the treatment of IE due to antibiotic resistant gram-positive cocci in the elderly population requires further investigation. Finally, the role of home therapy for elderly patients with IE needs further study. References 1. Von Reyn CF, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981; 94: Cunha BA, Gill MV, Lazar JM. Acute infective endocarditis: diagnostic and therapeutic approach. Infect Dis Clin North Am 1996; 10: Gagliardi JP, Nettles RE, McCarty DE, Sanders LL, Corey GR, Sexton DJ. Native valve infective endocarditis in elderly and younger adult patients: comparison of clinical features and outcomes with use of the Duke criteria and the Duke Endocarditis Database. Clin Infect Dis 1998; 26: Netzer RO, Zollinger E, Seiler C, Cerny A. Native valve infective endocarditis in elderly and younger adult patients: comparison of clinical features and outcomes with use of the Duke criteria. Clin Infect Dis 1999; 28: Pomerance A. Pathogenesis of aortic stenosis and its relation to age. Br Heart J 1972; 34: Lamas CC, Eykyn SJ. Bicuspid aortic valve a silent danger: analysis of 50 cases of infective endocarditis. Clin Infect Dis 2000; 30: Pomerance A. Pathological and clinical study of calcification of the mitral valve ring. J Clin Pathol 1970; 23: Werner GS, Schulz R, Fuchs JB, et al. Infective endocarditis in the elderly in the era of transesophageal echocardiography: clinical features and prognosis compared with younger patients. Am J Med 1996; 100: Leport C, Bure A, Leport J, Vilde JL. Incidence of colonic lesions in Streptococcus bovis and enterococcal endocarditis. Lancet 1987; 1(8535): Terpenning MS, Bradley SF, Wan JY, Chenoweth CE, Jorgensen KA, Kauffman CA. Colonization and infection with antibiotic-resistantbacteria in a long-term care facility. J Am Geriatr Soc 1994; 42: Felder RS, Nardone D, Palac R. Prevalence of predisposing factors for endocarditis among an elderly institutionalized population. Oral Surg Oral Med Oral Pathol 1992; 73: Terpenning MS, Buggy BP, Kauffman CA. Infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: Habte-Gabr E, January LE, Smith IM. Bacterial endocarditis: the need for early diagnosis. Geriatrics 1973; 28: Applefeld MM, Hornick RB. Infective endocarditis in patients over age 60. Am Heart J 1974; 88: Thell R, Martin FH, Edwards JE. Bacterial endocarditis in subjects 60 years of age and older. Circulation 1975; 51: Tenenbaum MJ, Kaplan MH. Infective endocarditis in the elderly: an update. Geriatrics 1984; 39:121 3, Gantz NM. Geriatric endocarditis: avoiding the trend toward mismanagement. Geriatrics 1991; 46: Selton-Suty C, Hoen B, Grentzinger A, et al. Clinical and bacteriological AGING AND INFECTIOUS DISEASES CID 2002:34 (15 March) 811

7 characteristics of infective endocarditis in the elderly. Heart 1997; 77: Cantrell M, Yoshikawa TT. Infective endocarditis in the aging patient. Gerontology 1984; 30: Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96: Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30: Bayer AS. Infective endocarditis. Clin Infect Dis 1993; 17: Daniel WG, Mugge A, Martin RP, et al. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med 1991; 324: Pedersen WR, Walker M, Olson JD, et al. Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. Chest 1991; 100: Sexton DJ, Tenenbaum MJ, Wilson WR, et al. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group. Clin Infect Dis 1998; 27: DiNubile MJ. Abbreviated therapy for right-sided Staphylococcus aureus endocarditis in injecting drug users: the time has come? Eur J Clin Microbiol Infect Dis 1994; 13: Small PM, Chambers HF. Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 1990; 34: Steckelberg JM, Murphy JG, Ballard D, et al. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med 1991; 114: Larbalestier RI, Kinchla NM, Aranki SF, Couper GS, Collins JJ Jr, Cohn LH. Acute bacterial endocarditis: optimizing surgical results. Circulation 1992; 86(5 Suppl):II Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98: Karp RB. Role of surgery in infective endocarditis. Cardiovasc Clin 1987; 17: Watanakunakorn C, Burkert T. Infective endocarditis at a large community teaching hospital, : a review of 210 episodes. Medicine (Baltimore) 1993; 72: Robbins N, DeMaria A, Miller MH. Infective endocarditis in the elderly. South Med J 1980; 73: Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. Circulation 1997; 96: CID 2002:34 (15 March) AGING AND INFECTIOUS DISEASES