【摘要】 目的:分析影响美罗培南药动学(PK)/药效学(PD)效应的主因子,探讨其常规方案用于常见革兰阴性杆菌感染的适宜性。方法:以美罗培南0.5 g q8h、1 g q8h和2 g q8h为模型方案,以50%fT>最低抑菌浓度(MIC)为PK/PD靶标,以大肠埃希菌(EC)、肺炎克雷伯菌(KP)、铜绿假单胞菌(PA)和鲍曼不动杆菌(AB)为目标菌种,以累积反应分数(CFR)为PK/PD效应指标,将药动学参数、给药参数和目标菌种的MIC分布整入PK/PD效应的数学模型(即%fT>MIC),利用蒙特卡洛模拟计算各方案在不同人群中通过0.5～3 h输注对各目标菌种的菌群达到靶标的CFR。通过敏感性分析探讨影响美罗培南PK/PD效应的主因子。结合CFR和效应的主因子及其特性探讨上述方案用于目标菌感染的适宜性。结果:影响美罗培南对EC和KP抗菌效果的主因子是个体化的药动学参数,但尽管如此,在考察的人群中(或考察的药动学参数下)即使美罗培南0.5 g q8h采取0.5 h输注也可对EC和KP达到≥90%的CFR。影响美罗培南对PA和AB抗菌效果的主因子是菌种的MIC分布。对PA,MIC分布是影响美罗培南PK/PD效应的主要因素,但并非决定因素。不论人群如何,大剂量美罗培南(2 g q8h)对PA仍可达到≥90%的CFR;但对AB,MIC分布则是影响美罗培南PK/PD效应的决定因素,即使2 g q8h也无法达到≥90%的CFR。结论:基于目前各目标菌种的MIC分布和效应影响因素的敏感性分析不同人群中美罗培南0.5 g q8h仍可用于EC和KP感染;对PA,则需采用2 g q8h;但对AB美罗培南常规方案可能无法获得良好的抗菌效果。更多还原

【Abstract】 Objective:To analyze the principal factors affecting the PK/PD of meropenem and explore the suitability of its conventional regimen against the infections resulting from the common gram-negative bacilli.Methods:Using meropenem 0.5 g q8 h,1 g q8 h,and 2 g q8 h as the modeled regimens,50% fT>MIC as the PK/PD targets,E.coli(EC),K.pneumonia(KP),P.aeruginosa(PA)and A.baumannii(AB) as the targeted species,and the cumulative fraction of response(CFR) as the PK/PD index,the pharmacokinetic parameters,dosing parameters and MIC distribution of targeted species were integrated into the mathematical model of PK/PD(i.e.,% fT>MIC),and Monte Carlo simulation was used to calculate the CFR of each regimen in different populations by 0.5-3 h infusion to reach the bacterial population of each targeted species.Results:The main factor affecting the antibacterial effect of meropenem on EC and KP was individualized pharmacokinetic parameters.However,in the population examined(or under the pharmacokinetic parameters investigated),CFR of≥90% could be achieved even within 0.5 h infusion of meropenem 0.5 g q8 h.The main factor affecting the antibacterial efficacy of meropenem against PA and AB was the MIC distribution of the species.For PA,MIC distribution was the major factor affecting the PK/PD of meropenem,while it was not the determinant.High-dose(2 g q8 h) of meropenem achieved≥90%CFR for PA regardless of population;however,for AB,MIC distribution was the determinant affecting the PK/PD of meropenem,and≥90% CFR was not achieved even with 2 g q 8 h.Conclusion:Based on the current MIC distribution of the species and sensitivity analysis of the factors affecting the PK/PD,meropenem 0.5 g q8 h can still be used for EC and KP infections in different populations;for PA,2 g q8 h is needed;however,for AB,currently common regimens of meropenem may not achieve a good antibacterial effect.更多还原