Antistaphylococcal activities of quinupristin/dalfopristin in vitro across platelet-fibrin matrices and in experimental endocarditis

In-vitro and in-vivo efficacies of quinupristin/dalfopristin and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) responsible for endocarditis have been compared. The following parameters were investigated: MIG, activity across a platelet-fibrin matrix simulating cardiac vegetations, killing of bacteria on the cardiac vegetations resulting from experimental aortic valve endocarditis in an animal model, and concentrations of antibiotics in the serum and vegetations of infected rabbits. The same bacterial strain was used for all experiments. The MICs of quinupristin/dalfopristin and vancomycin were 0.25 and 1 mg/L, respectively. When tested for their ability to penetrate platelet-fibrin matrices, both drugs were bactericidal against the MRSA strain (greater than or equal to 2 log(10) cfu/ml decrease in 2 h). Both drugs significantly reduced the bacterial counts in vegetations in infected rabbits. Within 12 h of intravenous administration of 20 mg/kg, concentrations of quinupristin/dalfopristin decreased from 5.3 to <0.10 mg/L in serum and from 12.9 to <1 mg/kg in the valve vegetations. Although the concentrations of vancomycin in the serum and the infected tissue were higher than those of quinupristin/dalfopristin, the latter combination was equally effective, perhaps because its bactericidal activity is rapid and because it can more easily penetrate the cardiac vegetations.