Aminoglycoside-containing antibiotic combinations for the treatment of bacterial endocarditis: an evidence-based approach.

This review deals with the question of whether the addition of an aminoglycoside to an antibiotic with activity against Gram-positive bacteria is safe and effective for the treatment of endocarditis. Aminoglycosides are more toxic than other drugs used in combination therapy for endocarditis, e.g. rifampicin. In the four randomised controlled trials that included patients with endocarditis and reported on this outcome, the relative risk for nephrotoxicity was 2.22 (95% CI 1.11-4.35). Given the high rates of significant nephrotoxicity we should ask whether sufficient evidence exists for the efficacy of combination therapy for the treatment of endocarditis. No randomised controlled trials have been conducted for most of the patients and pathogens for which combination therapy is recommended. In the few randomised controlled trials that have addressed the question, the addition of an aminoglycoside did not decrease fatality rate, clinical failure, need for operation or bacteriological failure. In clinical practice I would choose any option that is within the accepted boundaries (guidelines, textbooks, common practice) and does not include an aminoglycoside. Large randomised clinical trials are needed to answer this question; they need to include about 600 patients per patient/pathogen group and thus a multicentre, probably international, effort is needed.