Nakamura Tatsuya, Shimizu Chihiro, Kasahara Mayumi, Okuda Kazuyuki, Nakata Chiyo, Fujimoto Hiroko, Okura Hiroe, Komatsu Masaru, Shimakawa Kouichi, Sueyoshi Noriyuki, Ura Toshiro, Satoh Kaori, Toyokawa Masahiro, Wada Yasunao, Orita Tamaki, Kofuku Tomomi, Yamasaki Katsutoshi, Sakamoto Masako, Nishio Hisaaki, Kinoshita Shohiro, Takahashi Hakuo
Department of Clinical Laboratory, Kansai Medical University Hirakata Hospital, Osaka, Japan.
J Infect Chemother. 2009 Feb;15(1):13-7. doi: 10.1007/s10156-008-0656-6. Epub 2009 Mar 12.
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.
产超广谱β-内酰胺酶（ESBL）细菌因其底物特异性，对青霉素类、头孢菌素类和单环β-内酰胺类抗生素耐药，且这些细菌仅对窄谱抗菌药物敏感。本研究基于药代动力学/药效学（PK/PD）理论，采用蒙特卡罗模拟方法，评估碳青霉烯类抗生素和新型喹诺酮类抗生素对产ESBL大肠埃希菌的疗效。高于最低抑菌浓度时间（T＞MIC，%）作为碳青霉烯类抗生素的PK/PD参数，目标水平设定为40%。AUC/MIC作为新型喹诺酮类抗生素的PK/PD参数，目标水平设定为大于125。药敏分析结果显示，除亚胺培南外，其他碳青霉烯类抗生素的MIC50均较低（0.03μg/ml），而新型喹诺酮类抗生素的MIC50较高（1 - 2μg/ml）。蒙特卡罗模拟结果表明，在常规剂量水平下，除亚胺培南外，每种受试碳青霉烯类抗生素两剂给药后达到PK/PD目标的概率均较高（比阿培南为99.0%，美罗培南为99.60%，多利培南为95.03%）。在新型喹诺酮类抗生素中，帕珠沙星达到PK/PD目标的概率最高（42.90%）。因此，本研究结果表明，碳青霉烯类抗生素在常规剂量下有效，可作为产ESBL大肠埃希菌的首选抗生素，因为与新型喹诺酮类抗生素相比，碳青霉烯类抗生素的耐药率较低。
