基于蒙特卡洛模拟评价铜绿假单胞菌致血流及下呼吸道感染时阿米卡星的给药方案

目的:结合阿米卡星的PK/PD模型,运用蒙特卡洛模拟分别评价阿米卡星6种给药方案对铜绿假单胞菌引起的血流及下呼吸道感染的治疗效果。方法:收集我院2018-2019年临床标本血培养、痰培养分离出的铜绿假单胞菌并测得阿米卡星对其MIC值,运用蒙特卡洛模拟法分别模拟不同给药方案对“铜绿假单胞菌血流及下呼吸道感染患者”中5 000“例”的临床疗效,并计算各方案以IQ_max ≥ 10为目标阈值的CFR。结果:临床血标本、痰标本中分别分离出76和953株铜绿假单胞菌,其对阿米卡星的耐药率分别为3.95%、9.76%。对于血流感染,阿米卡星7.5,10.0,12.5 mg·kg^-1·d^-1给药剂量的CFR均小于90%;当铜绿假单胞菌MIC ≤ 1 mg·L^-1时,所有给药方案PTA均为100%,当MIC ≥ 8 mg·L^-1时,所有给药方案PTA均小于90%。对于下呼吸道感染,阿米卡星所有剂量的CFR均小于90%;当铜绿假单胞菌MIC ≤ 0.5 mg·L^-1时,所有给药方案PTA大于90%,当MIC ≥ 2 mg·L^-1时,所有给药方案PTA均小于90%。结论:痰培养铜绿假单胞菌对阿米卡星耐药率相对于血培养较高,阿米卡星经验治疗铜绿假单胞菌引起的血流感染时,我国指南阿米卡星推荐剂量能够达标,而经验治疗铜绿假单胞菌引起的下呼吸道感染时,国内外指南推荐剂量均不能达到满意的抗感染治疗效果,存在较大治疗失败风险。

Evaluation of therapeutic regimens on amikacin against Pseudomonas aeruginosa bloodstream and lower respiratory tract infection in patients by Monte Carlo simulation

OBJECTIVE To evaluate the therapeutic efficacy of amikacin in 6 dosing regimens against Pseudomonas aeruginosa bloodstream and lower respiratory tract infection using Monte Carlo simulation combined with amikacin PK/PD model.METHODS The Pseudomonas aeruginosa isolated from the blood and sputum culture of clinical specimens in our hospital from 2018 to 2019 was collected and the MIC value of amikacin was measured.Monte Carlo simulation method was used to simulate the clinical effect of different dosage regimens on 5 000 cases among patients with Pseudomonas aeruginosa bloodstream and lower respiratory tract infection,and the CFR targeting IQ_max ≥ 10 was calculated for each regimen.RESULTS 76 and 953 strains of Pseudomonas aeruginosa were isolated from clinical blood and sputum samples and their drug resistance rates to amikacin were 3.95% and 9.76% respectively.For bloodstream infections,when therapeutic regimen of amikacin was 7.5,10.0,12.5 mg·kg^-1·d^-1,the CFR was less than 90%.When MIC ≤ 1 mg·L^-1,the PTA of all therapeutic regimens of amikacin was 100%,and when the MIC ≥ 8 mg·L^-1,PTA of all therapeutic regimens of amikacin was less than 90%.For lower respiratory tract infection,CFR of all therapeutic regimens of amikacin was less than 90%.When MIC ≤ 0.5 mg·L^-1,the PTA of all therapeutic regimens of amikacin was greater than 90%,and when the MIC ≥ 2 mg·L^-1,PTA of all therapeutic regimens of amikacin was less than 90%.CONCLUSION The resistance rate of Pseudomonas aeruginosa to amikacin in sputum culture is higher than that in blood culture.When amikacin is used empirically to treat bloodstream infection caused by Pseudomonas aeruginosa,the recommended dose of amikacin in Chinese guidelines can meet the standard,while when it is used empirically to treat lower respiratory tract infection caused by Pseudomonas aeruginosa,the recommended dose in domestic and foreign guidelines cannot achieve satisfactory anti-infective therapeutic effect,with a greater risk of treatment failure.