EFFECTIVE TREATMENT OF MULTIDRUG-RESISTANT ENTEROCOCCAL EXPERIMENTAL ENDOCARDITIS WITH COMBINATIONS OF CELL WALL-ACTIVE AGENTS

The efficacy of treatment with a combination of ampicillin, imipenem, and vancomycin was compared with that of two-drug combinations or mono therapy in a model of experimental endocarditis using a strain of Ente rococcus faecium with high-level resistance to vancomycin and moderate intrinsic resistance to ampicillin and imipenem, In vitro time-kill s ynergy studies demonstrated bactericidal synergistic activity only for the triple combination, In vivo, monotherapy with vancomycin was not effective, Treatment with either ampicillin or imipenem alone or in co mbination with vancomycin resulted in <4 log(10) reduction in colony-f orming units (cfu) per gram of vegetation The combination of ampicilli n with imipenem was highly active (an additional 5 log(10) reduction i n cfu per gram of vegetation compared with the most active single agen t), but efficacy was not increased by the addition of vancomycin to am picillin and imipenem, Therapy with the combination of ampicillin and imipenem may be effective for some strains of multidrug-resistant ente rococcal infections.