多黏菌素B治疗危重症患者多药耐药革兰阴性菌感染的给药方案优化  

Dose Optimization of Polymyxin B in the Treatment of Multidrug-Resistant Gram-Negative Bacteria in Critically Ill Patients

作　　者：张祎景 陈姣姣 王楚慧 丘愈澜 滕蒙蒙 白楚琪 董亚琳[1] ZHANG Yijing;CHEN Jiaojiao;WANG Chuhui;QIU Yulan;TENG Mengmeng;BAI Chuqi;DONG Yalin(Dept.of Pharmacy,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院药学部,西安710061

出　　处：《中国医院用药评价与分析》2025年第2期153-156,160,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：陕西省创新能力支撑计划项目(No.2023-CX-PT-43)。

摘　　要：目的:优化多黏菌素B在危重症患者中的给药方案,为多黏菌素B的合理使用提供依据。方法:基于群体药动学模型和药动学/药效学靶标,使用蒙特卡洛模拟计算在不同体重危重患者中多黏菌素B不同给药方案的达标概率(PTA)及在3种病原菌中的累积反应分数(CFR)。认为PTA或CFR≥90%且肾毒性发生率<50%的最小剂量为最佳方案。结果:(1)多黏菌素B给予负荷剂量可以提高危重症患者第1日的PTA。(2)最低抑菌浓度(MIC)≤0.5 mg/L时,体重≥50 kg的患者推荐1.5 mg/kg的负荷剂量和0.5 mg/kg、每12 h给药1次的维持剂量,体重40~<50 kg患者的维持剂量需要增至0.75 mg/kg、每12 h给药1次。MIC=1 mg/L时,体重40~<50 kg的患者推荐2 mg/kg的负荷剂量和1.25 mg/kg、每12 h给药1次的维持剂量;体重50~<70 kg患者的维持剂量需减至1 mg/kg、每12 h给药1次;体重70~100 kg的患者推荐1.5 mg/kg的负荷剂量和0.5~0.75 mg/kg、每12 h给药1次的维持剂量。MIC=2 mg/L时,虽有给药方案可达标,但此时肾毒性发生率也较高,暂无推荐方案。(3)对于肺炎克雷伯菌或鲍曼不动杆菌感染,体重≥50 kg的患者建议1.5 mg/kg的负荷剂量和0.5 mg/kg、每12 h给药1次的维持剂量;对于铜绿假单胞菌感染,上述剂量仅适用于体重90~100 kg的患者,体重50~<70 kg的患者需要2 mg/kg的负荷剂量和1~1.25 mg/kg、每12 h给药1次的维持剂量,体重70~<90 kg的患者推荐1.5 mg/kg的负荷剂量和0.75 mg/kg、每12 h给药1次的维持剂量。结论:多黏菌素B在危重症患者中的给药方案应考虑患者特征及病原菌的类型和敏感性,必要时可进行治疗药物监测调整后续给药方案。OBJECTIVE:To optimize the administration of polymyxin B in critically ill patients,so as to provide evidence for rational use of polymyxin B.METHODS:Based on the population pharmacokinetic model and pharmacokinetic/pharmacodynamic target,Monte Carlo simulation was used to predict the probability of target achievement(PTA)for different dosing regimens and the cumulative response of fraction(CFR)of three bacteria in critically ill patients with different weights.The minimum dosage with PTA or CFR≥90%and the incidence of nephrotoxicity<50%was considered as the optimal regimen.RESULTS:(1)A loading dose could improve the PTA in critically ill patients in the first day.(2)When the minimum inhibitory concentration(MIC)was≤0.5 mg/L,the loading dose of 1.5 mg/kg and maintenance dose of 0.5 mg/kg every 12 hours were recommended for patients weighing≥50 kg,and the maintenance dose should be increased to 0.75 mg/kg every 12 hours for patients weighing 40 to<50 kg.When MIC was 1 mg/L,for patients weighing 40 to<50 kg,the loading dose of 2 mg/kg and maintenance dose of 1.25 mg/kg every 12 hours were recommended;for patients weighing 50 to<70 kg,the maintenance dose should be reduced to 1 mg/kg every 12 hours;for patients weighing 70 to 100 kg,the loading dose of 1.5 mg/kg and maintenance dose of 0.5 to 0.75 mg/kg every 12 hours were recommended.When MIC was 2 mg/L,although there were regimens that attained the target,the incidence of nephrotoxicity was higher,and no regimen was recommended.(3)For Klebsiella pneumoniae or Acinetobacter baumannii infection,the loading dose of 1.5 mg/kg and maintenance dose of 0.5 mg/kg every 12 hours were recommended for patients with body weight≥50 kg.For Pseudomonas aeruginosa infection,the above dosage was only suitable for patients weighing 90 to 100 kg,and patients weighing 50 to<70 kg need a loading dose of 2 mg/kg and maintenance dose of 1 to 1.25 mg/kg every 12 hours.The loading dose of 1.5 mg/kg and maintenance dose of 0.75 mg/kg every 12 hours were recommended for patients weig

关 键 词：多黏菌素B 危重症患者 多药耐药革兰阴性菌感染 药动学/药效学 给药方案优化 

分 类 号：R978.1[医药卫生—药品]