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Infective Endocarditis
Infective endocarditis has become more prevalent in the elderly despite the development of modern antibiotics. More than half of all cases of infective endocarditis occur in persons >60yrof age. Several factors account for the high prevalence in the elderly: increases in the total number of elderly persons and in the number with prosthetic valves, a higher prevalence of hospital-acquired bacteremia, longer survival o\’ persons with rheumatic valvular lesions, and fewer new cases of rheumatic heart disease.
Etiology
The underlying cardiac lesions that predispose Ihe elderly to endocarditis lend to differ from those in younger patients. The increased incidence of atherosclerosis in the elderly may be a factor, since atheromatous deposits can cause turbulence and. hence, thrombus formation. All forms of valvular disease increase the risk of endocarditis, although about 40% of elderly patients with endocarditis have either no valvular lesions or undetermined ones. Of the 60% who do have valvular disease, about 30% have rheumatic lesions, about 25% have calcified valves, and about 5% have mitral valve prolapse (see Ch. 38).
The aortic valve is involved in 20% to 40% of cases. The high incidence of aortic valve involvement probably reflects the increased prevalence of aortic stenosis with calcification in Ihe elderly. Until age 60. aortic stenosis with calcification is most commonly caused by rheumatic heart disease; from age 60 to 75, a calcified congenital bicuspid valve is most often implicated; and after age 75, degeneration of a normal valve is the leading cause. The mitral valve is involved in 25% to 70% of endocarditis cases, and both the aortic and mitral valves are involved in about 10% to 25%. Infections involving congenital heart defects other than those of Ihe bicuspid valve occur infrequently in the elderly.
The development of infective endocarditis involves 1 wo events. First is an alteration in the endocardial surface, which then permits the deposi-lion of platelets and fibrin. The resulting thrombus or vegetation most often arises in areas of increased turbulence. Second is transient bacteremia, which allows the thrombus to be colonized. The source of bacteremia is usually unknown. Sites of primary infection include the mouth, the GU tract (particularly afler procedures involving instrumentation), the GI tract, skin and decubitus ulcers, surgical wounds, and IV catheters.
Bacterial properties—eg. the increased adherence of certain streptococcal and staphylococcal species—-make some organisms more likely than others to cause infective endocarditis. Streptococcus spp are the most common, accounting for 25% to 70% of endocarditis cases, al-Ihough the viridans streptococci arc less prevalent in older than in younger populations. Enterococci, which often inhabit the GU and lower Gl tracts, can account for up to 25%’ of endocarditis cases in elderly men. Frequent urinary tract infections and procedures involving instrumentation (especially in men wilh prostate disease) explain the increased frequency of enterococcal bacteremia and endocarditis. S. bovis, a nonenterococcal group D streptococcus, can be isolated in up to 25% of endocarditis cases in persons > 55 yr. Many such cases are associated with underlying and often asymptomatic malignant or premalignant GI lesions, especially colon carcinoma.
Staphylococci account for 20% to 30% of all endocarditis cases in the elderly. The predominant species. Staphylococcus aureus, often causes nosocomial endocarditis, and many cases are discovered only incidentally at autopsy. 5- ep’tdermidis is isolated in < 5% of cases of native valve endocarditis, but in elderly as in younger patients, it is the most common single cause of cases involving prosthetic valves.
Gram-negative aerobic bacilli remain a rare cause of endocarditis (only 2% to i% of cases), often involving a prosthetic valve. Bacte-roides sppare rare isolates in older patients, as in younger ones. Mixed infections are rare in the elderly. Fungal endocarditis occurs in < 5% of cases: it is usually due to Candida sppor is secondary to fungemia from an indwelling intravascular catheter and often affects a prosthetic valve.
Culture-negative endocarditis, a suggestive clinical syndrome without an isolated organism, accounts for 10% to 20% of cases. The inability to isolate an organism from blood cultures may be due to prior antibiotic administration, fastidious pathogens, or inadequate laboratory techniques. Right-sided endocarditis and uremia are also associated with culture-negative endocarditis. More often, endocarditis is missed in Ihe elderly because the diagnosis is not considered.
Symptoms and Signs
The cl inical manifestations of infective endocarditis are diverse and may involve almost any organ system. Symptoms of endocarditis usually occur within 2 wk of the inciting bacteremia, although diagnosis may take much longer. Fever is the single most common finding. Nonspecific generalized complaints of anorexia, fatigue, confusion, weight loss, and night sweats are also common. Because the presentation is sometimes atypical (eg. without fever), infective endocarditis in the elderly may not be recognized and treated until it has progressed to a late stage. In these cases, it has an extremely poor prognosis.
On physical examination, cardiac murmurs are found in > 90% of patients, due to a predisposing valvular abnormality or to the infection itself. Murmurs are no! found in most patients with tricuspid valve endocarditis. New or changing cardiac murmurs are described in 36% to 52% of infective endocarditis cases diagnosed by strict clinical criteria, although these murmurs are heard less frequently in the elderly. The symptoms and signs of heart failure may also be presenl. occurring secondary to underlying heart disease or valvular destruction. Splenic enlargement occurs in 25% to 60% of patients, correlating with longer durations of infection.
About 50% of patients with infective endocarditis have cutaneous or peripheral manifestations. Petechiaearc most common, arising in crops and found on the conjunctivae, palate, buccal mucosa, extremities, and skin above the clavicles. Splinter hemorrhages appear as linear, dark streaks beneath the fingernails or toenails; however, these lesions are also common in noninfected elderly persons and in those with occupation-related trauma. Osier’s nodes—small, tender subcutaneous nodules that develop in the pulp of Ihe digits or on the thenar eminences— contrast with Janeway lesions—small, hemorrhagic, or erythematous nonlender macules on the palms or soles. Janeway lesions are due to septic emboli and are associated more often with acute endocarditis, especially that caused by 5. aureus. Ophthalmologic examination may reveal pale-centered, oval hemorrhages {Roth spots) on the retina. Although Roth spots are highly suggestive of infective endocarditis, they are also seen in patients with collagen-vascular and hematologic disorders.
Other clinical manifestations may involve other organ systems as a result of thromboembolic phenomena. Rmboli to the spleen may cause left upper quadrant abdominal pain radiating to the shoulder, a splenic friction rub, or signs of a left pleural effusion. Rmboli to Ihe kidney may cause flank or back pain, suggesting renal infarction. Patients with tricuspid valve endocarditis may develop pulmonary emboli and present with dyspnea, cough, pleuritic chest pain, and hemoptysis, especially if pulmonary infarction has occurred.
Cerebral embolism and rupture of an intracranial mycotic aneurysm are devastating complications, and the palient may present with the signs of a cerebrovascular accident; (his may distract the clinician from Ihe infectious cause of the disease. Fever and a stroke syndrome in any patient should warrant consideration of Ihe possibility of infective endocarditis. Most cerebral emboli involve the distribution of the middle cerebral artery or one of its branches. Clinical signs of emboli include hemiparesis. cranial nerve palsies, corticosensory loss, aphasia, ataxia, alterations in mental status, or a combination thereof. Persistent headache may be the only symptom signifying an intracranial mycotic aneurysm before rupture.
Diagnosis
The single most important laboratory finding in the diagnosis of infective endocarditis is bacteremia or fungemia. The bacteremia of endocarditis is usually continuous, and with few exceptions, blood cultures are positive. In patients who have not previously received antimicrobial therapy (the major reason for culture-negative endocarditis—see F.liol-ogy. above), negative blood cultures probably account for < 5% of endocarditis cases on native valves when blood cultures are handled by experienced laboratory personnel.
Laboratory analysis may show several nonspecific abnormalities. Anemia occurs in 70%’ to 90% of cases, worsens with duration of illness, and is usually characterized by normochromie-normocytic indices. However, patients with acute endocarditis often do not present with anemia. The ESR is elevated in 90% to 100%’ of patients. Urine cultures may reveal proteinuria (50%’ to 65% of cases) and microscopic hematuria (30% to 50% of cases). Racleriuria may occur when endocarditis is caused by enterococci or S. aureus. Up to 50% of patients with subacute bacterial endocarditis who have the infection for 6 wk have a positive rheumatoid factor, bill this is also seen in 24% of cases of acute S. aureus endocarditis in injection drug abusers. A positive rheumatoid factor must be interpreted cautiously in an aged patient because a significant liter is detected in 5% to 10% of healthy elderly people.
Echocardiography with Doppler ultrasonography has become the most accurate and widely used imaging modality in patients with suspected or proven endocarditis. Echocardiography is a sensitive and accurate method for detecting valvular vegetations, valvular destruction, and the hemodynamic sequelae of regurgitalion. The overall sensitivity of two-dimensional transthoracic echocardiography for detecting vegetations is about 80%. Because some older persons with valvular sclerosis have focal thickening on one or more valvular structures, valve masses are not synonymous with vegetations.
Transesophageal echocardiography is more sensitive than the transthoracic approach for detecting vegetations; it is parlicularly helpful in patients in whom the standard transthoracic approach to imaging is difficult (eg, those with emphysema, prosthetic valves, or poor transthoracic windows, or those on mechanical ventilators). Transesophageal echocardiography can also demonstrate multiple vegetations, satellite lesions, fistulas, ring abscesses, valvular perforations, and aneurysms when transthoracic echocardiography shows only the vegetation.
Prophylaxis
Antibiotic prophylaxis is indicated in older patients with valvular disease, particularly those with calcified and prosthetic heart valves, who arc at especially high risk for developing endocarditis. Preventing infective endocarditis will assume even greater importance as the percentage of elderly persons in the population increases and as more persons have prosthetic valves implanted, undergo invasive diagnostic and therapeutic procedures with a potential for bacteremia, and retain their native dentition.
Treatment
Choosing an appropriate antimicrobial agent is of primary importance in the successful management of infective endocarditis. Bactericidal agents must be given for optimal therapy. In acutely ill patients, empiric therapy should be started immediately after obtaining blood cultures to limit valvular damage.
Treatment is based on the likely infecting microorganism in the specific clinical setting. A subacute presentation in a non-injection drug abuser with native valves suggests infection with streptococci or en-terococci. and the standard empiric regimen should consist of high-dose IV penicillin G (or ampicillin) combined with gentamicin. In acute-onset disease or in an injection drug abuser, therapy should target S. aureus. In non-drug abusers with native valves, a penicillinase-resistant penicillin (eg. nafcillin) or a cephalosporin (eg, ceiazolin) is appropriate initial therapy. However, in injection drug abusers, many strains of S. aureus arc resistant to all β-laclam antibiotics, and vancomycin is the empiric agent of choice. If the patient has a prosthetic valve, therapy is initially directed at S. aureus and 5. epidernu’dis. Because many strains of 5. epidermidis are resistant to β-laclam antibiotics, vancomycin is the agent of choice.
Once the infecting microorganism is isolated from blood cultures and susceptibility testing is performed, the antimicrobial regimen should be altered to provide the therapy that is most effective with the Icasl toxicity and cost (see TABLE 39-1). Peak and trough antibiotic concentrations should be ascertained to ensure that blood concentrations are appropriate for elderly patients, since excretory and metabolic functions are often impaired. Therapy is continued for at least 2 wk longer in patients with prosthetic valves.
Some patients with infective endocarditis may need valve replacement (see VALVE REPLACEMENT in Ch. 44). Indications for surgery are hemodynamic deterioration from valve dysfunction, fungal endocarditis, persistent infection despite appropriate antimicrobial therapy, repeated relapses after completion of therapy, early postoperative prosthetic valve endocarditis, intracardiac extension of the infection, “complicated” prosthetic valve endocarditis, and recurrent emboli. With appropriate preoperative assessment and preparation, valve replacement can be safely performed in the elderly patient.