Initial empirical treatment of endocarditis is penicillin plus gentamicin or, if there is an acute aggressive onset, flucloxacillin (or similar) plus gentamicin. Patients with prosthetic valves should be treated with a glycopeptide plus an aminoglycoside with or without rifampin. If blood cultures remain negative, it is probable that the patient has received previous antibiotics. The nutritionally deficient streptococci, HACEK organisms, anaerobes, Brucella species, and Listeria species may take a week or more to be recognized in culture. Rarely, failure to respond to penicillin and gentamicin may be the result of infection with Coxiella, Bartonella, or Chlamydia species, and serological tests are required. Fungal endocarditis may appear culture negative. Surgical management will be necessary if there is no response in the presence of clear vegetations on echocardiography. Collagen vascular diseases, sarcoidosis, malignancy, tuberculosis, and viral infections (including HIV) should be eliminated. Recurrence of fever after an initial response may be caused by the antibiotic itself and resolves after a change of treatment. Coxiella infection requires prolonged treatment with doxycycline, possibly for life, and surgery is often necessary.
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