Pharmacodynamics of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with rifampin, against methicillin-susceptible and -resistant Staphylococcus aureus in an in vitro infection model
Abstract
The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively) in an in vitro infection model. The incidence of the emergence of resistance among the test strains was also determined. The fluoroquinolones were administered to simulate dosage regimens of 200 mg, 400 mg given intravenously (i.v.) every 12 h (q12h), and 400 and 800 mg given i.v. q24h. Rifampin was dosed at 600 mg i.v. q24h. Although the MICs and MBCs of the quinolones were similar (< or = 0.49 microgram/ml), levofloxacin was the most potent agent in time-kill studies on the basis of the time required to achieve a 99.9% reduction in the number of log10 CFU per milliliter (e.g., with the regimen of levofloxacin [400 mg q24h, 6.5 h] versus ofloxacin [12.5 h], P < 0.024, and levofloxacin versus ciprofloxacin [6.5 versus 9.0 h], P < 0.0017) against MSSA 1199. The killing activity of levofloxacin was similar to that of ofloxacin against MRSA 494 (time to achieve a 99.9% reduction in the number of log10 CFU per milliliter, 11.1 versus 13.8 h, respectively). Levofloxacin and ofloxacin dosed once daily demonstrated greater bactericidal activity than when they were dosed twice daily against MSSA 1199. Resistance to levofloxacin or ofloxacin was not observed with any…
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