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[基于蒙特卡洛模拟法探讨头孢他啶抗铜绿假单胞菌感染的优化方案]

[Investigation on optimal regimen of ceftazidime against infection caused by Pseudomonas aeruginosa using Monte Carlo simulation].

作者信息

Mikamo Hiroshige

机构信息

Department of Infection Control and Prevention, Aichi Medical University.

出版信息

Jpn J Antibiot. 2007 Dec;60(6):387-93.

PMID:18447208
Abstract

An optimal regimen for the use of ceftazidime (CAZ) (one of injectable antimicrobial agents in cephem family) against Pseudomonas aeruginosa infection was explored, using Monte Carlo simulation. Pharmacokinetic parameters needed for Monte Carlo simulation were derived from the existing data for healthy adults, and the data on MIC distribution of CAZ against clinically isolated bacterial strains reported by Working Group of Forum on Microbial Resistance. When CAZ was used within the currently approved dosage and administration for adults (4 g/day at maximum), intravenous administration of CAZ, 1 g, t.i.d., per day was found to have the highest probability to achieve the target of maximum bactericidal activity for cephems, i.e., 60-70%T > MIC (time above MIC). The probability to achieve the same target was the second highest with two intravenous CAZ, 2 g, b.i.d., per day, and third with CAZ, 1 g, b.i.d., per day. These results suggest that when treating P. aeruginosa infection with CAZ, for which T > MIC serves as PK/PD parameter, increasing the frequency of dosing is effective method to reinforce its efficacy, and that CAZ, t.i.d., per day is an optimal dosage and administration within the range of the regimens described in its package insert.

摘要

利用蒙特卡洛模拟法,探索了头孢他啶(CAZ,头孢菌素类注射用抗菌药物之一)治疗铜绿假单胞菌感染的最佳给药方案。蒙特卡洛模拟所需的药代动力学参数取自健康成年人的现有数据,以及微生物耐药性论坛工作组报告的CAZ对临床分离菌株的MIC分布数据。当按照目前批准的成人剂量和给药方式(最大剂量为4g/天)使用CAZ时,发现每天静脉注射3次、每次1g的CAZ给药方式最有可能达到头孢菌素最大杀菌活性目标,即60 - 70%T > MIC(高于MIC的时间)。达到相同目标的概率,每天静脉注射2次、每次2g的CAZ给药方式排第二,每天静脉注射2次、每次1g的CAZ给药方式排第三。这些结果表明,当以T > MIC作为药代动力学/药效学参数,用CAZ治疗铜绿假单胞菌感染时,增加给药频率是增强其疗效的有效方法,并且每天3次给药的CAZ给药方式是其说明书所述给药方案范围内的最佳剂量和给药方式。

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