title: Evaluation by Monte Carlo simulation of levofloxacin dosing for complicated urinary tract infections caused by Escherichia coli or Pseudomonas aeruginosa.
abstract: We evaluated, by Monte Carlo simulation, 500-mg once-daily, 100-mg thrice-daily, 200-mg twice-daily, and 200-mg thrice-daily dose regimens of levofloxacin (LVFX), for the ratio of area under the concentration-time curve for 24 h (AUC(0-24)) to minimum inhibitory concentration (MIC) (AUC(0-24)/MIC) and the ratio of maximum plasma concentration (C(max)) to MIC (C(max)/MIC), which predict microbiological outcomes, and the C(max)/MIC, which inhibits fluoroquinolone resistance selection, in complicated urinary tract infections (UTIs) with Escherichia coli or Pseudomonas aeruginosa. Monte Carlo simulation was performed for 10000 cases using the pharmacokinetic data of patients with complicated UTIs and the LVFX MIC distributions for E. coli or P. aeruginosa clinical strains. The probabilities of achieving the AUC(0-24)/MIC target (66.2-67.9%) and the C(max)/MIC target (64.5-67.5%) to eradicate E. coli were similar among the 4 regimens. In eradication of P. aeruginosa, the 200-mg thrice-daily and the once-daily dose regimens produced higher probabilities of achieving the AUC(0-24)/MIC target (57.5%) and C(max)/MIC target (55.1%), respectively. For the probabilities of achieving the C(max)/MIC targets that prevent the emergence of fluoroquinolone resistance, the once-daily dose regimen (66.8%) did not differ from the other multiple-dose regimens (62.3-66.2%) in E. coli, whereas the former regimen (44.2%) was superior to the latter regimens (10.8-31.7%) in P. aeruginosa. The 500-mg once-daily dose regimen of LVFX, which produced the larger AUC(0-24) and higher C(max), could ensure the efficacy of eradication of uropathogens and reduce the risk of fluoroquinolone resistance selection in complicated UTIs.
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan. deguchit@gifu-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.forename: Kensaku
authors.initials: K
authors.lastname: Seike
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yasuda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D003198:Computer Simulation; D016208:Databases, Factual; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D009010:Monte Carlo Method; D015242:Ofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin