title: The antibacterial efficacy of levofloxacin and ciprofloxacin against Pseudomonas aeruginosa assessed by combining antibiotic exposure and bacterial susceptibility.
abstract: Ciprofloxacin has a four-fold greater in-vitro activity than levofloxacin against Pseudomonas aeruginosa, but levofloxacin has a four-fold higher area under the serum concentration-time curve (AUC) for an equivalent dose. It has been proposed that the AUC/MIC ratio is a general predictor of antibacterial efficacy for quinolones. Using an in-vitro kill curve technique, performed in quadruplicate, with nine antibiotic concentrations and three strains of P. aeruginosa with varying quinolone susceptibility, we constructed sigmoidal dose-response curves for AUC(0-6.5)/MIC and area under the bacterial kill curve (AUBKC) or AUC(0-24)/MIC and log change in viable count at 24 h (delta24). For levofloxacin the log AUC(0-6.5)/MIC ratio to produce 50% of the maximal effect was 0.74 +/- 0.13 (r2 = 0.9435) for levofloxacin and 0.82 +/- 0.06 (r2 = 0.7935) for ciprofloxacin. The log AUC(0-24)/MIC ratio to produce 50% maximal effect was 1.58 +/- 0.13 (r2 = 0.7788) for levofloxacin and 1.37 +/- 0.12 (r2 = 0.7207) for ciprofloxacin. An AUC(0-24)/MIC ratio of 125 produced 85.4% of the maximal response with levofloxacin and 81.5% with ciprofloxacin. These data suggest that levofloxacin and ciprofloxacin have equivalent activity against P. aeruginosa at equivalent AUC/MIC ratios.
authors.affiliation: Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
authors.forename: M
authors.initials: M
authors.lastname: Wootton
authors.forename: H A
authors.initials: HA
authors.lastname: Holt
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin