Ongoing efforts to promote the appropriate treatment of skin infections in this population are warranted. The association of USA300 colonization or infection and drug use with sexual partners suggest a role for sexual transmission of the USA300 strain of MRSA.
Deep-seated infections caused by strains of methicillinresistant Staphylococcus aureus are becoming a major problem (5). Present medical therapy for these infections requires long-term intravenous administration of vancomycin (10). Development of an orally absorable antimicrobial agent with activity against strains of methicillin-resistant S. aureus will represent a major breakthrough in the treatment of deepseated infections caused by this organism. Enoxacin is a new antimicrobial agent of the quinolone class (2). It combines good bactericidal activity against strains of methicillinresistant S. aureus with levels in serum and tissue after oral administration which are higher than the MICs for the majority of these organisms (3, 11).The endocarditis model in rabbits is a severe test of the efficacy of antimicrobial agents for deep-seated infections. The purpose of this study was to compare the therapeutic efficacy of enoxacin administered orally with that of vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.
MATERIALS AND METHODSOrganism. The methicillin-resistant S. aureus strain used in this study (1116) was a clinical isolate from a patient with bacteremia and was kindly supplied by the Warner-Lambert Pharmaceutical Co., Ann Arbor, Mich. It was proven to be methicillin resistant by its ability to grow on Mueller-Hinton agar containing 20 ,ug of methicillin per ml. Stock cultures were made by incubating the organism in Mueller-Hinton broth (MHB) at 37°C for 24 h and storing 1-ml samples at -20°C. For each experiment, a sample was subcultured into MHB and incubated at 37°C for 18 h.
* Corresponding author.In vitro studies. The MICs and MBCs of enoxacin and vancomycin were determined with an inoculum of 5.0 x i05 CFU of methicillin-resistant S. aureus per ml of MHB as described previously (9). The MIC was defined as the lowest concentration of antimicrobial agent that prevented turbidity after 24 h of incubation at 37°C. The MBC was defined as the lowest concentration of antimicrobial agent that killed at least 99.9% of the organisms within 24 h, as determined by plating portions of the MIC dilutions.The survival of a large inoculum of methicillin-resistant S. aureus was studied in flasks with MHB containing enoxacin at 6 ,ug/ml, vancomycin at 180 ,ug/mnl, and MHB alone. These concentrations of enoxacin and vancomycin were similar to peak levels in serum achieved in rabbits after one dose of enoxacin at 100 mg/kg administered orally and after one dose of vancomycin at 30 mg/kg administered intravenously. An inoculum of approximately 108 CFU/ml of MHB was added to each flask and incubated at 37°C. Samples were removed at 0, 3, 6, and 24 h.
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