Clinical implications of pharmacokinetics and pharmacodynamics of fluoroquinolones.
This review summarizes key data illustrating the clinical importance of pharmacodynamics, particularly among the fluoroquinolone family of antibacterials. Antibacterials are often divided into 2 groups--either time-dependent or concentration-dependent agents--on the basis of their mechanism of killing. Fluoroquinolones are concentration-dependent agents, and the parameter that correlates most closely with clinical and/or bacteriological success is the ratio of the area under plasma concentration curve (AUC) to the minimum inhibitory concentration (MIC). The AUC : MIC threshold may vary by organism. For example, a ratio of at least 30 is often cited as optimal to achieve success against Streptococcus pneumoniae, whereas higher ratios (>100) are considered to be optimal for the treatment of infections due to gram-negative bacilli. Data are cited to suggest that the minimum ratio necessary to prevent the selection of resistant mutants may, in fact, be somewhat higher. Maximizing the AUC : MIC through the use of potent therapy may offer an opportunity to limit the development of resistance to fluoroquinolones.
Wispelwey
Brian
B
University of Virgina School of Medicine, Charlottesville, Virginia 22908, USA. bwg9@virginia.edu
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D008954:Models, Biological; D009010:Monte Carlo Method; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013997:Time Factors
D000890:Anti-Infective Agents; D024841:Fluoroquinolones