Application of fluoroquinolone pharmacodynamics

Pharmacodynamics provides a rational basis for optimizing dosing regimens by describing the relationship between drug, host and antimicrobial effect. The successful identification of meaningful pharmacodynamic outcome parameters can, therefore, greatly assist clinicians in making objective prescribing decisions rather than relying on static in vitro MIC data. While pharmacodynamic outcome parameters have been proposed for select antimicrobial agents, their clinical application remains to be defined fully. Quinolone antibiotics are generally considered to have concentration-dependent bactericidal activity and peak/MIC and AUC/MIC ratios have been identified as possible pharmacodynamic predictors of clinical and microbiological outcome as well 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 derived primarily from studies of Gram-negative bacteria, and recent data suggest that these ratios may not be applicable for Streptococcus pneumoniae, where an AUC/MIC ratio of <40 appears to be a more accurate predictor. There is considerable variation in pharmacodynamic calculations and outcome parameters appear to be quinolone- and pathogen-specific. Additional prospective clinical research is needed to characterize quinolone pharmacodynamic parameters and answer unresolved questions regarding optimal pharmacodynamic outcome predictors for Gram-positive bacteria, anaerobes and atypical respiratory pathogens.