中国临床药学杂志2025，Vol.34Issue(2)：93-99,7.DOI:10.19577/j.1007-4406.2025.02.003
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
摘要
Abstract
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Key words
Monte Carlo simulation/pharmacokinetics/pharmacodynamics/meropenem/Gram-negative bacilli/optimized two-step infusion/prolonged infusion/traditional infusion分类
药学引用本文复制引用
吕楠,岳宝森,张炜华,孙丹,崔玮..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[J].中国临床药学杂志,2025,34(2):93-99,7.基金项目
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) （编号2023-1-1-4）
西安市中医医院院级科研课题(编号2024YJ09) （编号2024YJ09）
陕西省重点研发计划(编号2023-YBSF-066) （编号2023-YBSF-066）
