基于群体药动学和药效学模型优化成人重症患者的比阿培南给药方案

Optimization of dosage regimens of biapenem in adult critical patients based on population pharmacokinetics/pharmacodynamics model

目的优化肠杆菌科细菌感染成年重症患者比阿培南给药方案。方法基于群体药动学/药效学(PK/PD)模型,结合中国细菌耐药监测数据,采用蒙特卡洛模拟,计算肠杆菌科细菌感染成年重症患者比阿培南18种给药方案治疗达标概率(PTA)和累积反应分数(CFR),优化给药方案。结果以40%fT>MIC作为目标靶值,当最低抑菌浓度MIC≥4 mg/L时,比阿培南所有给药方案PTA<90%;对于大肠埃希菌所有给药方案CFR>90%;针对肺炎克雷伯菌,600 mg q12h、q8h、q6h持续静脉输注,600 mg q8h和q6h 3 h静脉输注给药方案CFR值分别为89.85%、89.70%、89.80%、89.40%、89.73%。结论对于ICU重症患者,比阿培南300 mg q12h,0.5～1 h静脉滴注方案可用于大肠埃希菌感染的经验性治疗,而针对肺炎克雷伯菌的感染,推荐采用600 mg q8h 3 h、600 mg q6h 3 h静脉输注经验性治疗或根据最低抑菌浓度(MIC)制定目标治疗方案。

Objective To optimize the dosage regimens of biapenem against Enterobacteriaceae Bacteria infection in adult critical patients.Methods Based on population pharmacokinetics/pharmacodynamics(PK/PD)model,and report from China antimicrobial resistance surveillance trial program,the probability of target attainment(PTA)and cumulative fraction of response(CFR)of 18 dosage regimens of biapenem were obtained by using Monte Carlo simulation,and then the optimal dosage regimens were determined.Results When the PK/PD target value employed was 40% fT>MIC and MIC≥4 mg/L,the PTAs of all biapenem regimens were less than 90%;the CFRs of these regimens were more than 90% against Escherichia coli(E.coli);the CFRs of biapenem 600 mg q12h,q8h and q6h continuous infusion,and 600 mg q8h/q6h 3 h infusion were 89.85% ,89.70% ,89.80% ,89.40% and 89.73% against Klebsiella pneumoniae(K.pneumoniae),respectively.Conclusion Biapenem 300 mg q12h 0.5~1 h infusion can be used for the experiential therapy for E.coli infection in adult critical patients;for patients with K.pneumoniae infection,600 mg q8h/q6h 3 h infusion regimens are recommended as the experiential therapy,or target therapy of biapenem should be performed according to MICs.