应用蒙特卡罗模拟优化MRSA感染患者给药方案

Optimization of dosing regimens in MRSA infected patients by Monte Carlo simulation

目的:对MRSA感染患者不同给药方案进行蒙特卡罗模拟评价给药方案。方法:将万古霉素、替考拉宁、利奈唑胺和替加环素各种给药方案进行5 000次蒙特卡罗模拟,将得到的达标概率(PTA)和累积反应分数(CFR)进行比较。结果:万古霉素(2 g·d^(-1),3 g·d^(-1))的CFR分别为58.46%和90.79%;替考拉宁(0.4 g·d^(-1),0.8 g·d^(-1))的CFR分别为65.37%和98.64%;利奈唑胺(1.2 g·d^(-1))的CFR为49.27%;替加环素(100 mg·d^(-1),200 mg·d^(-1))的CFR分别为96.46%和100%。结论:替加环素最有可能达到所需的CFR。对于糖肽类药物来说,增加给药剂量可以获得较好的CFR。对于利奈唑胺来说,当MIC>1 mg·L^(-1)时,需要增加给药剂量或改用其他药物。

OBJECTIVE To optimize dosing regimens in MRSA infected patients using Monte Carlo simulation.METHODSA5 000-patient Monte Carlo simulation was conducted to estimate the probability of target attainment（PTA）and cumulative fraction of response（CFR）for vancomycin,teicoplanin,linezolid and tigecycline.RESULTS The estimated CFRs were58.46% and 90.79%for vancomycin（2 g·d^-1,3 g·d^-1）,65.37% and 98.64% for teicoplanin（0.4 g·d^-1,0.8 g·d^-1）,49.27%for linezolid,96.46% and 100%for tigecycline（100 mg·d^-1,200 mg·d^-1）.CONCLUSION Tigecycline has a greater probability to achieve its CFR.Higher doses improve CFRs for both glycopeptides.With MIC1 mg·L^-1,higher dose of linezolid or switching to other drug is necessary to improve efficacy.