title: Comparative anti-staphylococcal effects of gemifloxacin and trovafloxacin in an in vitro dynamic model in terms of AUC/MIC and dose relationships.
abstract: To compare the antimicrobial effects of gemifloxacin and trovafloxacin on Staphylococcus aureus, their pharmacodynamics were studied in an in vitro dynamic model. A series of pharmacokinetic profiles of gemifloxacin and trovafloxacin with half-lives of 7.4 and 9.2 h, respectively, were simulated in vitro over an eightfold range of area under the curve (AUC)-to-MIC ratio, from 58 to 466 h. The relationships observed between the intensity of antimicrobial effect (I(E)) and log AUC/MIC were linear, species- and strain-independent and were distinct (not superimposed) for both gemifloxacin and trovafloxacin (r(2) = 0.99 in both cases). At AUC/MICs > 100 h, trovafloxacin had greater effects than gemifloxacin. For example, at an AUC/MIC of 250 h, the antimicrobial effect of trovafloxacin was 17% higher than gemifloxacin. However, due to its higher intrinsic activity, gemifloxacin may be as efficient as trovafloxacin at their clinical doses (320 and 200 mg, respectively): the I(E)s on a hypothetical strain of S. aureus with gemifloxacin's and trovafloxacin's MICs corresponding to the MIC(50)s were similar-290 and 310 (log CFU/mL)x h, respectively. This analysis suggests that both AUC/MIC and dose relationships of the antimicrobial effect are needed for comprehensive comparisons of fluoroquinolone pharmacodynamics.
authors.affiliation: Department of Medicine, Mount Auburn Hospital, Cambridge, MA, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Zinner
authors.forename: S N
authors.initials: SN
authors.lastname: Vostrov
authors.forename: I Y
authors.initials: IY
authors.lastname: Lubenko
authors.forename: Y A
authors.initials: YA
authors.lastname: Portnoy
authors.forename: G
authors.initials: G
authors.lastname: Cornaglia
authors.forename: A A
authors.initials: AA
authors.lastname: Firsov
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011237:Predictive Value of Tests; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin; D000077735:Gemifloxacin