The pharmacodynamics of gatifloxacin and ciprofloxacin for pneumococci in an in vitro dynamic model: prediction of equiefficient doses.

Enhanced activity against Streptococcus pneumoniae is one of the putative advantages of gatifloxacin over older fluoroquinolones such as ciprofloxacin. This study examined ciprofloxacin and gatifloxacin pharmacodynamics against two differentially susceptible clinical isolates of S. pneumoniae (gatifloxacin MIC, 0.125 and 2 mg/L; ciprofloxacin MIC, 1 and 32 mg/L). The pharmacokinetics of gatifloxacin (single dose) and ciprofloxacin (two 12 hourly doses) with half-lives of 6 and 5 h, respectively, were simulated using a two-compartment dynamic model. The AUC/MIC ratios in the peripheral compartments that contain bacterial cultures varied over a four- to five-fold range, from 11 to 48 h with ciprofloxacin and from 15 to 78 h with gatifloxacin. The intensity of the antimicrobial effect (IE) increased with increasing AUC/MIC ratios in a strain-independent fashion, although different relationships of IE to log AUC/MIC were inherent for each drug (r2 0.73 for gatifloxacin and r2 0.94 for ciprofloxacin). Subsequently, the respective dose-response relationships of gatifloxacin and ciprofloxacin for a hypothetical strain of S. pneumoniae with MIC equal to the MIC50 were modelled. Based on these relationships, the equiefficient doses of gatifloxacin and ciprofloxacin were predicted for MIC50S of 0.4 and 1 mg/L, respectively. Gatifloxacin 400 mg was predicted to be equiefficient to ciprofloxacin 1400 mg. To provide the same anti-pneumococcal effect as the usual 1000 mg daily dose of ciprofloxacin, the respective daily dose of gatifloxacin could be as low as 180 mg. This in vitro study demonstrates advantages of gatifloxacin relative to ciprofloxacin in terms of the dose-dependent total antimicrobial effect.