title: Clinical implications of pharmacokinetics and pharmacodynamics of fluoroquinolones.
abstract: 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.
authors.affiliation: University of Virgina School of Medicine, Charlottesville, Virginia 22908, USA. bwg9@virginia.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Wispelwey
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones