PK/PD模型结合蒙特卡洛模拟评价和优化耐碳青霉烯类铜绿假单胞菌抗菌药物给药方案

目的： 评价和优化耐碳青霉烯类铜绿假单胞菌感染抗菌药物给药方案。方法： 收集中山市人民医院2019年耐碳青霉烯类铜绿假单胞菌对头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星耐药监测报告，确定头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星治疗方案，根据各抗菌药物的PK/PD模型，运用蒙特卡洛模拟计算4种抗菌药物不同给药方案的达标概率（PTA）和累积反应分数（CFR），评价疗效和优化出最佳初始给药方案。结果： 4种抗菌药物15种给药方案CFR均<90%。当最低抑菌浓度（MIC）≤ 2 μg·mL^-1时，4种抗菌药物常规剂量下的给药方案均能达到满意的治疗效果，当MIC ≤ 16 μg·mL^-1时，可目标性选择头孢他啶2 g（q8h）、头孢吡肟2 g（q8h）和哌拉西林钠他唑巴坦4.5 g（q8h）给药方案治疗，当MIC=32 μg·mL^-1时，只有哌拉西林钠他唑巴坦4.5 g（q6h）给药方案PTA>90%，当MIC>32 μg·mL^-1时，所有给药方案PTA均<90%。4种抗菌药物MIC值的敏感相关性为范围-88.9%~-96.7%。结论： 在CRPA感染经验性治疗时，单药治疗并不能达到满意的抗感染治疗效果，应考虑联合用药，可选用较高剂量和增加给药频次的抗假单胞菌β内酰胺类抗菌药联合阿米卡星。MIC值是影响4种抗菌药物治疗效果的最主要因素，临床上应重视细菌耐药的培养，可根据MIC值调整给药方案进行目标治疗。

Evaluation and optimization of antibacterial drugs dosage regimens of carbapenem resistant Pseudomonas aeruginosa infection by PK/PD model combined with Monte Carlo simulation

OBJECTIVE To evaluate and optimize the dosing regimen of carbapenem-resistant P.aeruginosa infections.METHODS The surveillance reports of carbapenem-resistant Pseudomonas aeruginosa resistance to ceftazidime,cefepime,piperacillin sodium and tazobactam and amikacin in our hospital in 2019 were collected to determine the treatment regimens of ceftazidime,cefepime,piperacillin sodium and tazobactam and amikacin.According to the PK/PD model of each antibacterial drug,Monte Carlo simulation was used to calculate the PTA and CFR of different dosing regimens of the four antibacterial drugs,evaluate the efficacy and optimize the optimal initial dosing regimen.RESULTS CFR was<90% for 15 dosing regimens of the four antimicrobial agents.When MIC ≤ 2 μg·mL^-1,four kinds of antibacterials regimens at regular doses could have satisfactory therapeutic effect,when MIC ≤ 16 μg·mL^-1,ceftazidime 2 g(q8h),cefepime 2 g(q8h)and piperacillin tazobactam 4.5 g(q8h)could be selected as the target therapy.When MIC=32 μg·mL^-1only the dosing regimen of piperacillin sodium and tazobactam 4.5 g(q6h)had PTA>90%.When MIC was more than 32 μg·mL^-1,all dosage regimens' PTA were less than 90%.The sensitivity of MIC of the four kinds of antibacterials ranged from-88.9% to-96.7%.CONCLUSION In the empirical treatment of CRPA infection in our hospital,the treatment does not achieve satisfactory anti-infective therapeutic effect and will be at a high risk of treatment failure.The combination of drugs should be considered,and the combination of antipseudomonal β-lactam antibacterial drugs at higher dose and dosing frequency can be considered.MIC value is the most important factor affecting the therapeutic effect of the four antibacterial drugs.The culture of bacterial resistance should be emphasized in clinical practice,and the dosing regimen can be adjusted according to MIC value for target treatment.