Pharmacodynamic assessment of the activity of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against clinical strains of Pseudomonas aeruginosa.
The objective of this study was to comparatively evaluate specific bacterial killing ability of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against 2 clinical isolates of Pseudomonas aeruginosa (PA-21 and PA-2105). An in vitro pharmacodynamic modeling apparatus was used to expose the P. aeruginosa isolates to total peak concentrations and elimination characteristics associated with each quinolone. All experiments were conducted over 24 h, and a subsequent dose of ciprofloxacin was given at 12 h to emulate twice-daily dosing. Respective 3-log reductions in PA-24 occurred after 0.6, 1.0, and 2.6 h for levofloxacin, ciprofloxacin, and gatifloxacin; regrowth was seen with all 3 agents, but was greatest with gatifloxacin. PA-2105 had 2- to 4-fold higher minimal inhibitory concentrations (MICs) than PA-24. Gatifloxacin failed to achieve a 3-log reduction. Levofloxacin and ciprofloxacin took roughly 3.5 h to decrease initial inoculum by 3 logs, but regrowth of PA-2105 followed. Simulated doses of levofloxacin and ciprofloxacin showed comparable activity against each study isolate; less activity was observed with gatifloxacin. Levofloxacin versus PA-24 was the only regimen that approached the desired AUC/MIC(0-24) ratio of greater than 100-125 and achieved the targeted peak/MIC ratio of > or =8. Although quinolones are typically used in combination with other antibiotics for P. aeruginosa, differences in activity favor the use of levofloxacin or ciprofloxacin for the study isolates. Use of gatifloxacin may contribute to the increased rate of quinolone-resistant P. aeruginosa.
Garrison
Mark W
MW
College of Pharmacy, Department of Pharmacotherapy, Washington State University, Spokane, WA 99210-1495, USA. garrism@wsu.edu
D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D005069:Evaluation Studies as Topic; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin