Infective Endocarditis

Infection of the heart valves or mural endocardial myocardium, resulting in the formation of endocardial vegetations.

Infective endocarditis has become more prevalent among the elderly. More than one fourth of all cases occur in persons > 60 years. Prevalence has increased because the number of elderly persons and of persons with prosthetic valves has increased, hospital-acquired bacteremia has become more prevalent, and persons with valvular heart disease survive longer. Infective endocarditis affects eight times as many elderly men as elderly women.

Etiology and Pathophysiology

The underlying cardiac lesions that predispose the elderly to endocarditis tend to differ from those in younger patients. Calcification of the mitral or aortic annulus with insufficiency is more common among the elderly, whereas congenital heart defects are more common among younger persons. The increased incidence of atherosclerosis in the elderly may be a factor, because atheromatous deposits in valves can cause turbulence, resulting in endothelial damage and thrombus formation. About 30% of elderly patients with endocarditis have rheumatic lesions, about 25% have calcified valves, and about 5% have mitral valve prolapse; however, about 40% have unidentified or no valvular lesions. All forms of valvular heart disease increase the risk of endocarditis.

The aortic valve is involved in 20 to 40% of elderly patients with infective endocarditis, probably reflecting the high prevalence of aortic stenosis with calcification. Aortic stenosis with calcification is most commonly caused by rheumatic heart disease in persons < 50, by a calcified congenital bicuspid valve in those aged 50 to 65, and by degeneration of a normal valve in those > 65. Infective endocarditis involves the mitral valve in 25 to 70% of patients and both the aortic and mitral valves in about 10 to 25%. Endocarditis involving congenital heart defects other than those of the bicuspid valve occur infrequently in the elderly.

The development of infective endocarditis requires two conditions: The first is an alteration in the endocardial surface, allowing the deposition of platelet and fibrin. The resulting thrombus or vegetation usually develops in areas of jet impingement and increased turbulence and acts as a site for bacterial attachment. The second condition is bacteremia, which results in colonization of the lesion. The source of bacteremia is usually unknown. Sites of primary infection include the mouth, the genitourinary (GU) tract (particularly after procedures involving instrumentation), the gastrointestinal (GI) tract, the skin, decubitus ulcers, surgical wounds, and IV catheters.

Some bacteria have certain properties (eg, certain streptococcal and staphylococcal species have increased adherence) that make them more likely to cause infective endocarditis. Streptococcus sp account for 25 to 70% of cases; viridans streptococci are less prevalent among elderly than among younger patients. Enterococci, which often inhabit the GU and lower GI tracts, account for up to 25% of cases in elderly patients. The prevalence of enterococcal bacteremia and endocarditis is high because urinary tract infections are common among the elderly and procedures involving instrumentation are frequently performed, especially in men with prostate disorders. S. bovis, a nonenterococcal group D streptococcus, is isolated in up to 25% of patients > 55 who have endocarditis. Many cases involving S. bovis are associated with underlying, often asymptomatic malignant or premalignant GI lesions, especially colon cancer.

Staphylococci account for 20 to 30% of all cases of endocarditis in the elderly. The predominant species, Staphylococcus aureus, often causes nosocomial endocarditis. S. epidermidis is isolated in < 5% of patients with native valve endocarditis, but it is the most common cause of cases that involve prosthetic valves occurring early after surgery in elderly and in younger patients. Gram-negative aerobic bacilli and fungi cause 2 to 3% of all cases of endocarditis. Infections due to Bacteroides sp and mixed infections are rare among the elderly.

Culture-negative endocarditis accounts for 5 to 20% of all cases of endocarditis; culture results may be negative because of prior antibiotic administration, fastidious pathogens, or inadequate laboratory techniques. Uremia is associated with an increased incidence of culture-negative endocarditis.

The pathophysiology of infective endocarditis is due to the body's reaction to the infection: the development of antibodies to the foreign protein of the organism, with resultant immune complex disease; systemic emboli; and valvular disruption and regurgitation. The hemodynamic clinical picture depends on how rapidly valvular regurgitation develops and how severe it is.

Symptoms and Signs

Clinical manifestations are diverse and may involve almost any organ system. Symptoms and signs usually occur within 2 weeks of the bacteremia. Fever is the most common sign. Anorexia, fatigue, confusion, back pain, weight loss, and night sweats are also common. Elderly patients may present atypically, with no fever, unexplained anemia, large systemic emboli, renal failure, and central nervous system syndromes (eg, rapid-onset dementia, stroke).

During physical examination, cardiac murmurs, due to a preexisting valvular abnormality or to the infection itself, are heard in > 90% of patients. New or changing cardiac murmurs occur in 36 to 52% of all patients with infective endocarditis diagnosed by strict clinical criteria but occur less frequently in the elderly. Signs of heart failure may also be present. Splenic enlargement occurs in 25 to 60% of patients; the increasing incidence is associated with a longer duration of endocarditis.

About 40% of patients have cutaneous or peripheral manifestations. Petechiae are the most common, occurring in crops on the conjunctivae, palate, buccal mucosa, extremities, and skin above the clavicles. Splinter hemorrhages (linear, dark streaks) occur beneath the fingernails or toenails but are also common among elderly persons who do not have infective endocarditis. Osler nodes (small, raised, tender subcutaneous nodules in the pads of the digits or on thenar eminences) and Janeway lesions (small, nontender hemorrhagic or erythematous macules on the palms or soles) may occur. Roth's spots (pale-centered oval hemorrhages in the retina) suggest infective endocarditis but also occur in patients with collagen vascular disease or hematologic disorders.

Other clinical manifestations may result from thromboemboli. Emboli 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. Emboli to the kidneys may cause flank or back pain, suggesting renal infarction. Large emboli obstructing large arteries, such as the external iliac, superficial femoral, and brachial arteries, are characteristic of endocarditis caused by fungi or HACEK organisms (Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae).

Cerebral embolism and rupture of an intracranial mycotic aneurysm (which may be presaged only by persistent headache) are devastating complications. The patient may present with signs of a stroke (eg, hemiparesis, cranial nerve palsies, cortical sensory loss, aphasia, ataxia, alteration in mental status), which may distract the clinician from identifying the infectious cause of the disease. Infective endocarditis should be considered in any patient with a fever and a stroke syndrome. Most cerebral emboli involve the distribution of the middle cerebral artery or one of its branches.

Diagnosis

Often, endocarditis, especially culture-negative endocarditis, is missed in the elderly because the diagnosis is not considered. When patients present atypically, infective endocarditis may not be recognized and treated until it has progressed to a late stage. Such patients have an extremely poor prognosis.

The most important laboratory finding is a positive blood culture result, which is found in about 90% of patients. Because bacteremia is continuous in infective endocarditis, the timing of the culture in relation to occurrence of fever is usually unimportant. Laboratory tests may detect anemia (in 70 to 90%), elevated ESR (in 90 to 100%), proteinuria (in 50 to 65%), and microscopic hematuria (in 30 to 50%). Rheumatoid factor is commonly detected in patients who have been infected for > 6 weeks but is also present in 5 to 10% of healthy elderly persons.

Doppler echocardiography is very valuable. It can detect valvular vegetations, valvular destruction, extravalvular infection (annular abscesses), and the hemodynamic sequelae of regurgitation. In the elderly, valvular masses are not synonymous with vegetations and may result from valvular sclerosis or myxomatous degeneration of the valve. Transesophageal echocardiography is helpful when the standard transthoracic approach to imaging is too difficult technically or is not diagnostic. It can detect multiple vegetations, satellite lesions, fistulas, annular abscesses, valvular perforations, and aneurysms when transthoracic echocardiography shows only a vegetation.

Prophylaxis and Treatment

Antibiotic prophylaxis is indicated in elderly patients with valvular heart disease, particularly in patients with calcified or prosthetic heart valves and particularly before certain procedures (see Table 90-1).

Optimal treatment requires use of microbicidal drugs. For acutely ill patients, empiric therapy should be started immediately after obtaining blood for culture, so that valvular damage can be limited.

Initially, selection of antimicrobial therapy is based on which microorganism is most likely in the specific clinical setting. If onset is subacute in a patient who does not use IV drugs and who has native valve endocarditis, infection with streptococci or enterococci is likely. The standard empiric regimen consists of high-dose IV penicillin G (or ampicillin) with an aminoglycoside such as gentamicin. If onset is acute or if the patient uses IV drugs, therapy should target S. aureus. If onset is acute in a patient who does not use IV drugs and who has native valve endocarditis, a penicillinase-resistant penicillin (eg, nafcillin) or a cephalosporin (eg, cefazolin) is appropriate initial therapy. If the patient has a prosthetic valve, vancomycin can be used to target resistant strains of S. aureus and S. epidermidis.

After the infecting microorganism is identified, antimicrobial therapy is altered accordingly, to the most effective, least toxic, and least costly regimen (see Table 90-2). Therapy is continued at least 2 weeks longer if patients have prosthetic valves.

Some patients with infective endocarditis need valve replacement. Indications for valve replacement are hemodynamic deterioration due to valve dysfunction, fungal endocarditis, persistent infection despite appropriate antimicrobial therapy, repeated relapses after completion of therapy, early postoperative or complicated endocarditis involving a prosthetic valve, extravalvular extension of the infection, and recurrent emboli.