INTRODUCTION

Prior to the availability of antimicrobial therapy, infective endocarditis (IE) was invariably fatal. Although approximately 80 percent of patients with endocarditis now survive their infections, one of every six patients with IE does not survive the initial hospitalization, and up to one-third of patients infected with highly virulent organisms (such as Staphylococcus aureus) may die as a direct or indirect result of their valvular infection [1]. An adverse outcome in these patients can occur despite having received appropriate antimicrobial therapy in a timely manner, and despite the skillful use of modern diagnostic techniques.

The major issues related to the antimicrobial therapy of IE will be reviewed here. The pathogenesis of vegetation formation and the complications and indications for surgery in this disorder are discussed separately. (See "Pathogenesis of vegetation formation in infective endocarditis" and "Complications and outcome of infective endocarditis" and "Surgery for native valve endocarditis".)

GENERAL CONSIDERATIONS

Soon after the discovery of sulfonamides and penicillins, it was realized that only bactericidal, not bacteriostatic, therapy was effective in treating endocarditis. Thus, following the establishment of a diagnosis using microbiologic and echocardiographic methods, or by clinical deduction, antimicrobial therapy should be administered in a dose designed to give sustained bactericidal serum concentrations throughout much of the entire dosing interval. In vitro determination of the minimum inhibitory concentration or other susceptibility testing of the etiologic cause of the endocarditis should be performed in all patients. (See "Infective endocarditis: Historical and Duke criteria".)

Empiric therapy — In general, therapy for infective endocarditis (IE) should be targeted to the organism isolated from blood cultures; cultures are positive in over 90 percent of patients with IE. For patients with suspected IE who present without acute symptoms, empiric therapy is not always necessary, and therapy can await blood culture results. Results of blood cultures are usually available within one to three days, and an accurate diagnosis is a critical first step in designing a management strategy. (See "Diagnostic approach to infective endocarditis".)

For acutely ill patients with signs and symptoms strongly suggestive of IE, empiric therapy may be necessary. Such empiric therapy should be administered ONLY after at least two (preferably three) sets of blood cultures have been obtained from separate venipunctures, and ideally spaced over 30 to 60 minutes. The choice of empiric therapy in such cases should take into consideration the most likely pathogens. In general, empiric therapy should cover staphylococci (methicillin-susceptible and resistant), streptococci, and enterococci. Vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose) is an appropriate choice for initial therapy in most patients.