Penicillinase-resistant penicillins plus gentamicin in experimental enterococcal endocarditis

Previous in vitro studies demonstrating that the penicillinase-resistant penicillins act synergistically in combination with gentamicin against some enterococci have suggested that these combinations might be effective therapy for enterococcal infections in vivo. To determine the in vivo effectiveness of such combinations, we treated rabbits with enterococcal endocarditis with gentamicin and either nafcillin, oxacillin, or methicillin. Despite doses of the penicillins equivalent to 12 or 24 g/day in a 70-kg patient, the percentage of animals in each treatment group with sterile valves at autopsy after spontaneous death or sacrifice after 21 days of therapy was low. High-dose therapy with the penicillins did not significantly increase survival over the low-dose treatment groups. Thus, it seems prudent to include penicillin with a penicillinase-resistant penicillin and gentamicin as the initial therapy of patients with endocarditis possibly caused by enterococci.