Efficacies of moxifloxacin, ciprofloxacin, and vancomycin against experimental endocarditis due to methicillin-resistant Staphylococcus aureus expressing various degrees of ciprofloxacin resistance

The new 8-methoxyquinolone moxifloxacin was tested against two ciprofloxaci n-susceptible Staphylococcus aureus strains (strains P8 and COL) and two ci profloxacin-resistant derivatives of strain P8 carrying a single grl4 mutat ion (strain P8-4) and double grlA and gyrA mutations (strain P8-128). All s trains were resistant to methicillin. The MICs of ciprofloxacin and moxiflo xacin were 0.5 and 0.125 mg/liter, respectively, for P8; 0.25 and 0.125 mg/ liter, respectively, for COL; 8 and 0.25 mg/liter, respectively, for P8-4; and greater than or equal to 128 and 2 mg/liter, respectively, for P8-128. In vitro, the rate of spontaneous resistance of P8 and COL was 10(-7) on ag ar plates containing ciprofloxacin at two times the MIC, whereas it was les s than or equal to 10(-10) on agar plates containing moxifloxacin at two ti mes the MIC. Rats with experimental aortic endocarditis were treated with d oses of drugs that simulate the kinetics in humans: moxifloxacin, 400 mg or ally once a day; ciprofloxacin, 750 mg orally twice a day; or vancomycin, I g intravenously twice a day. Treatment was started either 12 or 24 h after infection and lasted for 3 days. Moxifloxacin treatment resulted in cultur e-negative vegetations in a total of 20 of 21 (95%) rats infected with P8, 10 of 11 (91%) rats infected with COL, and 19 of 24 (79%) rats infected wit h P8-4 (P < 0.05 compared to the results for the controls). In contrast, ci profloxacin treatment sterilized zero of nine (0%) vegetations infected wit h first-level resistant mutant P8-4. Vancomycin sterilized only 8 of 15 (53 %), 6 of 11 (54%), and 12 of 23 (52%) of the vegetations, respectively. No moxifloxacin-resistant derivative emerged among these organisms. However, m oxifloxacin treatment of highly ciprofloxacin-resistant mutant P8-128 faile d and selected for variants for which the MIC increased two times in 2 of 1 0 animals. Thus, while oral moxifloxacin might deserve consideration as tre atment for staphylococcal infections in humans, caution related to its use against strains for which MICs are borderline is warranted.