Fluoroquinolone susceptibility, resistance, and pharmacodynamics versus clinical isolates of Streptococcus pneumoniae from Indiana

The in vitro activity and pharmacodynamics (AUC(0-24)/MIC) of levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin were evaluated against 307 clinical isolates of Streptococcus pneumoniae from Indianapolis, Indiana. Organisms were collected between January 1999 and April 2000, and MICs were determined by broth microdilution. Serum concentration-time profiles were simulated for the following oral regimens administered once daily: levofloxacin 500 mg and 750 mg; gatifloxacin 400 mg; moxifloxacin 400 mg; gemifloxacin 320 mg. Free 24 h area under the serum concentration-time curves (AUC(0-24)) were calculated, and the average AUC(0-24)/MIC was calculated for each regimen. Differences in AUC(0-24)/MIC among agents were determined by analysis of variance (Scheffe post-hoc test, p < 0.05). Overall, gemifloxacin was the most potent agent tested. Five (1.7%), 4 (1.3%), and 2 (0.7%) isolates were resistant to levofloxacin, gatifloxacin, and moxifloxacin, respectively. None of the isolates was resistant to gemifloxacin. Gemifloxacin AUC(0-24)/MIC was significantly greater than all other regimens (p < 0.0001), with the exception of moxifloxacin. However, the percent of isolates for which an AUC(0-24)/MIC greater than or equal to 30-50 can be achieved is similar for gemifloxacin, moxifloxacin, gatifloxacin, and levofloxacin 750 mg. Large comparative studies are needed to determine if the differences in AUC(0-24)/MIC among fluoroquinolones are clinically significant. (C) 2001 Elsevier Science Inc. All rights reserved.