Comparative in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae

STUDY OBJECTIVE: To compare in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae. DESIGN: In vitro analysis. SETTING: University research laboratory. INTERVENTION: Minimum inhibitory concentrations (MICs) were determined for penicillin and five fluoroquinolones by E test for 201 S. pneumoniae isolates. Serum concentration-time profiles were simulated for the following regimens: ciprofloxacin 750 mg orally every 12 hours and 400 mg intravenously every 8 hours; levofloxacin 500 mg orally and intravenously every 24 hours; trovafloxacin 200 mg orally and intravenously every 24 hours; gatifloxacin 400 mg orally and intravenously every 24 hours; and clinafloxacin 200 mg orally and intravenously every 12 hours. MEASUREMENTS AND MAIN RESULTS: Free 24-hour areas under the serum concentration-time curves (AUC0-24) were calculated using the trapezoidal rule, and the average AUC0-24:MIC ratio was calculated for each regimen. Differences in ratios among agents were determined by analysis of variance (Scheffe post hoc test, p < 0.05). For intravenous dosing, the average AUC0-24:MIC for gatifloxacin, clinafloxacin, trovafloxacin, ciprofloxacin, and levofloxacin was 146, 142, 122, 71, and 61, respectively. For both oral and intravenous regimens, gatifloxacin and clinafloxacin ratios were significantly greater than those for trovafloxacin, levofloxacin, and ciprofloxacin (p < or = 0.007). Ratios for trovafloxacin were significantly greater than those for levofloxacin and ciprofloxacin (p < 0.0001), and levofloxacin and ciprofloxacin ratios were not significantly different from each other. CONCLUSION: Gatifloxacin and clinafloxacin achieve significantly higher AUC0-24:MIC ratios for S. pneumoniae than trovafloxacin, levofloxacin, and ciprofloxacin. Large comparative studies are necessary to determine the clinical significance of these findings.