title: Monte Carlo simulation for evaluation of the efficacy of carbapenems and new quinolones against ESBL-producing Escherichia coli.
abstract: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are known to be resistant to penicillins, cephalosporins, and monobactams because of their substrate specificity, and these bacteria are sensitive only to a narrow range of antimicrobial agents. The present study was undertaken to evaluate the efficacy of carbapenems and the new quinolones against ESBL-producing Escherichia coli, using a Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic (PK/PD) theory. The time above MIC (TAM, %) served as the PK/PD parameter for carbapenems, with the target level set at 40%. The AUC/MIC served as the PK/PD parameter for the new quinolones, with the target level set at more than 125. In the analysis of drug sensitivity, the MIC50 of all carbapenems other than imipenem was low (0.03 microg/ml), while the MIC50 of the new quinolones was higher (1-2 microg/ml). The probability of achieving the PK/PD target with carba penems after two doses at the usual dose level, as determined by the Monte Carlo simulation, was high for each of the carbapenems tested (99.0% for biapenem, 99.60% for meropenem, and 95.03% for doripenem), except for imipenem. Among the new quinolones, the highest probability of achieving the PK/PD target was obtained with pazufloxacin (42.90%). Thus, the results of the present study have revealed that carbapenems are effective at the regular dose and can be used as the first-choice antibiotics for ESBL-producing E. coli because the resistance ratios for carbapenems are low compared to those of the new quinolones.
authors.affiliation: Department of Clinical Laboratory, Kansai Medical University Hirakata Hospital, Osaka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimizu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kasahara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Okuda
authors.forename: Chiyo
authors.initials: C
authors.lastname: Nakata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Hiroe
authors.initials: H
authors.lastname: Okura
authors.forename: Masaru
authors.initials: M
authors.lastname: Komatsu
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shimakawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sueyoshi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ura
authors.forename: Kaori
authors.initials: K
authors.lastname: Satoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Toyokawa
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Wada
authors.forename: Tamaki
authors.initials: T
authors.lastname: Orita
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kofuku
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Masako
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Nishio
authors.forename: Shohiro
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Hakuo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D015363:Quinolones; D001618:beta-Lactamases