Microbiological outcome of complicated urinary tract infections treated with levofloxacin: a pharmacokinetic/pharmacodynamic analysis.
The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined in patients with complicated urinary tract infections (UTIs) treated with 500mg of levofloxacin every 24h for 7-14 days. Of 241 pre-treatment strains from 156 patients, 21 strains persisted after treatment. In each patient, plasma concentrations of levofloxacin were simulated based on population pharmacokinetic parameters and patient-specific data. Minimum inhibitory concentrations (MICs) of levofloxacin for the pre-treatment strains determined in our previous study were used. The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined by logistic regression analyses. For all the isolates, Gram-negative bacilli, Gram-positive cocci, Escherichia coli and Enterococcus faecalis, the target values of the area under the concentration-time curve (AUC)/MIC were 14.65, 31.46, 4.85, 43.00 and 3.06, respectively, and the targets of the maximum plasma concentration (C(max))/MIC were 1.22, 2.74, 0.39, 3.61 and 0.25, respectively. Such thresholds of AUC/MIC and C(max)/MIC in complicated UTIs would be lower than those in infections of other sites. In particular, the C(max)/MIC thresholds for Gram-positive cocci and E. faecalis were <1. These findings suggested that, in addition to its plasma concentration, the high concentration of levofloxacin in the urine might play a role in eradicating bacteria.
Deguchi
Takashi
T
Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. deguchit@gifu-u.ac.jp
Nakane
Keita
K
Yasuda
Mitsuru
M
Shimizu
Takako
T
Monden
Koichi
K
Arakawa
Soichi
S
Matsumoto
Tetsuro
T
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology*; D014556:Urine / Q000737:chemistry
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin