Application of fluoroquinolone pharmacodynamics

Pharmacodynamics provides a rational basis for optimizing dosing regimens b y describing the relationship between drug, host and antimicrobial effect. The successful identification of meaningful pharmacodynamic outcome paramet ers can, therefore, greatly assist clinicians in making objective prescribi ng decisions rather than relying on static in vitro MIC data. While pharmac odynamic outcome parameters have been proposed for select antimicrobial age nts, their clinical application remains to be defined fully. Quinolone anti biotics are generally considered to have concentration-dependent bactericid al activity and peak/MIC and AUC/MIC ratios have been identified as possibl e pharmacodynamic predictors of clinical and microbiological outcome as wel l as the development of bacterial resistance. Investigators have suggested that AUC/MIC ratios of greater than or equal to 100-125 or peak/MIC ratios of >10 are required to predict clinical and microbiological success and to limit the development of bacterial resistance. These conclusions are derive d primarily from studies of Gram-negative bacteria, and recent data suggest that these ratios may not be applicable for Streptococcus pneumoniae, wher e an AUC/MIC ratio of <40 appears to be a more accurate predictor. There is considerable variation in pharmacodynamic calculations and outcome paramet ers appear to be quinolone- and pathogen-specific. Additional prospective c linical research is needed to characterize quinolone pharmacodynamic parame ters and answer unresolved questions regarding optimal pharmacodynamic outc ome predictors for Gram-positive bacteria, anaerobes and atypical respirato ry pathogens.