产超广谱β-内酰胺酶菌感染治疗方案的优化

Optimization of β-Lactam Treatment Regimens for Extended-spectrum β-Lactamases-producing Strains Infections Based on Pharmacokinetics/pharmacodynamics

目的运用药动学/药效学(PK/PD)方法,对产超广谱β-内酰胺酶(ESBLs)菌感染的β-内酰胺治疗方案进行优化比较。方法采用蒙特卡洛模拟,依PK/PD模拟7种β-内酰胺类抗菌药物的14种给药方案,对产ESBLs大肠埃希菌和肺炎克雷伯菌的累积反应分数(CFR)。结果模拟获得的抑菌/抗菌CFR,以0.5 g 1次/8 h亚胺培南/西司他丁和0.5 g 1次/8 h美罗培南最高(100.0%);3.375 g 1次/4 h哌拉西林/他唑巴坦对产ESBLs大肠埃希菌的抑菌/杀菌CFR>90.0%;头孢曲松(1 g 1次/24 h、2 g 1次/24 h)、头孢他啶(1 g 1次/8 h、2 g1次/8 h)、头孢吡肟(1 g 1次/8 h、1 g 1次/12 h2、g 1次/8 h)和头孢哌酮/舒巴坦(0.5 g 1次/8 h1、g 1次/8 h、2 g 1次/8 h)治疗方案,对产ESBLs菌的CFR明显小于非产ESBLs菌,增加给药剂量和次数未能有效提高CFR。结论PK/PD模拟可优化抗感染治疗的给药方案,为精确用药提供指导。

OBJECTIVE To optimize and compare the β-lactam treatment regimens for extended-spectrum β- lactamases （ESBLs）-producing strains infections by means of pharmacokinetics/pharmacodynamic （PK/PD）. METHODS The Monte Carlo model was used to simulate the cumulative fractions of response （CFR） of 14 dosing regimens of 7 β-lactams against Escherichia coli and Klebsiella pneumoniae using the pharmacodynamic bacteriostatic/bactericidal targets of f% T〉 MIC. RESULTS The bacteriostatic/bactericidal CFR of 0.5g q8h imipenem/cilastatin and 0. 5g q8h meropenem were the highest （100%） ; that of 3. 375g q4h sodium piperacillin/ tazobactam sodium against ESBLs-producing E. coli was above 90%; the CFRs of ceftriaxone （1g q24h, 2g q24h）, ceftazidime （1g q8h, 2g q8h）, cefepime （1g q8h, 1g q12h, 2g q8h） and cefoperazone sodium/sulbactam （0.5g q8h, 1g q8h, 2g q8h） against ESBLs-producing strains were clearly less than those of non-ESBLs-producing ones, and the CFRs could not be effectively improved with the dose and frequency increased. CONCLUSIONS The PK/PD simulation is useful to optimize the regimen of anti-infective treatment, and guide its dosing accurately.