应用PK/PD理论及蒙特卡罗模拟评价美罗培南治疗常见革兰阴性杆菌感染的给药方案  

Evaluating the dosage regimens of meropenem for the treatment of common Gram-negative bacilli infections based on PK/PD theory and Monte Carlo simulation

作　　者：吕楠 岳宝森 张炜华 孙丹 崔玮 LYU Nan;YUE Baosen;ZHANG Weihua;SUN Dan;CUI Wei(Department of Pharmacy,Xi'an Hospital of Traditional Chinese Medicine,Xi'an 710021,China)

机构地区：[1]西安市中医医院药剂科,西安710021

出　　处：《中国临床药学杂志》2025年第2期93-99,共7页Chinese Journal of Clinical Pharmacy

基　　金：陕西省药学会医院药学高质量发展研究项目(编号2023-1-1-4);西安市中医医院院级科研课题(编号2024YJ09);陕西省重点研发计划(编号2023-YBSF-066)。

摘　　要：目的评价美罗培南应用传统输注法(TIT)、延长输注法(PIT)和优化两步输注法(OTIT)在不同给药剂量及输注时间条件下治疗医院常见革兰阴性杆菌感染的效果,为临床抗感染方案的制订及优化提供参考。方法收集2022-2023年医院革兰阴性杆菌对美罗培南的药敏试验结果,以抗菌药物的药动学/药效学理论为基础,应用蒙特卡罗模拟获取美罗培南治疗4种医院常见革兰阴性杆菌(大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌)的39种具体给药方案的达标概率(PTA)与累积反应分数(CFR),以PTA≥90%/CFR≥90%为条件选择最佳目标性/经验性治疗给药方案。结果PIT及OTIT可获得较TIT更高的PTA和CFR,延长输注时间可提升PTA与CFR。当美罗培南的最低抑菌浓度(MIC)≤0.5 mg·L^(-1)或考虑大肠埃希菌感染时建议使用PIT且输注时间至少3~4 h;当美罗培南的MIC为1~4 mg·L^(-1)或考虑肺炎克雷伯菌、铜绿假单胞菌感染时推荐选用OTIT且第二步输注时间至少5~6 h。结论临床应用美罗培南时不建议使用TIT,而PIT及OTIT的给药方式的选择、输注时间的长短取决于细菌对美罗培南的敏感度,OTIT更适用于治疗美罗培南MIC较高菌细引起的重症感染,在此基础上延长输注时间可进一步提升抗感染治疗效果。AIM To evaluate the therapeutic efficacy of meropenem for the treatment of common Gram-negative bacilli in hospitals by applying traditional infusion therapy(TIT),prolonged infusion therapy(PIT),and optimized two-step infusion therapy(OTIT)with different dosages and infusion times,and provide reference for the formulation and optimization of anti-infective regimens in clinical practice.METHODS The antimicrobial susceptibility testing results of Gram-negative bacilli to meropenem in the hospital from 2022 to 2023 were collected.Based on the pharmacokinetics/pharmacodynamics theory of antimicrobial agents,Monte Carlo simulation was applied to obtain the probability of target attainment(PTA)and cumulative fraction of response(CFR)of 39 dosing regimens of meropenem for the treatment of 4 common Gram-negative bacilli(Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa and Acinetobacter baumannii isolates)in the hospital.The optimal target/empirical therapeutic dosage regimens were selected using PTA≥90%/CFR≥90%criteria.RESULTS PIT and OTIT could obtain higher PTA and CFR than TIT.Extended infusion durations demonstrated enhanced PTA and CFR outcomes.Selected PIT and at least infusion 3-4 h were recommended when meropenem minimum inhibitory concentration(MIC)values≤0.5 mg·L^(-1)or Escherichia coli infection was considered.Selected OTIT and the second-step infusion phase lasting 5-6 h were recommended when 1 mg·L^(-1)≤MIC≤4 mg·L^(-1)or Klebsiella pneumoniae and Pseudomonas aeruginosa infection were considered.CONCLUSION TIT is not recommended for application of meropenem in clinical therapy.The administration mode of PIT and OTIT,along with the duration of infusion time,depends on the sensitivity of bacteria to meropenem.OTIT is more suitable for treating severe infections caused by bacteria with higher MIC values of meropenem.Under such conditions,further prolongation of infusion time may optimize anti-infective therapeutic efficacy.

关 键 词：蒙特卡罗模拟 药动学/药效学 美罗培南 革兰阴性杆菌 优化两步输注 延长输注 传统输注 

分 类 号：R978[医药卫生—药品]