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目的用蒙特卡洛软件模拟并优化去甲万古霉素在不同肾功能患者中的给药方案。方法用二倍稀释法确定临床分离菌株的最低抑菌浓度(MIC),以AUC0-24/MIC≥638为靶值,在不同肾功能患者、不同剂量下,利用蒙特卡洛软件进行10 000次模拟,得到相应的目标获得概率(PTA)和累积反映分数(CFR)。结果肾功能正常患者,治疗粪肠球菌和屎肠球菌感染,在推荐剂量(0.8~1.6g·d-1)下,CFR均小于59.77%;当剂量调整为2.5 g·d-1时,CFR才达到83.95%和73.10%。中度肾损伤患者,治疗粪肠球菌感染时,在0.8 g·d-1时,CFR可达82.81%;治疗屎肠球菌感染时,在0.8~2.5 g·d-1时,CFR可达73.10%~86.84%。重度肾损伤患者,治疗屎肠球菌和粪肠球菌感染时,在0.4g·d-1时,CFR可达97.77%和85.90%。结论蒙特卡洛模拟得出药物的给药方案,补充并优化了去甲万古霉素的给药方案。
Objective To simulate and optimize the administration of norvancomycin in patients with different renal functions using Monte Carlo software. Methods The minimum inhibitory concentration (MIC) of clinically isolated strains was determined by two-fold dilution. The AUC0-24 / MIC≥638 was used as the target value in different renal function patients and under different doses with Monte Carlo software for 10,000 times The simulation results in the corresponding PTA and CFR scores. Results The CFR of patients with normal renal function and the activity of Enterococcus faecalis and Enterococcus faecium were less than 59.77% at the recommended dose (0.8-1.6 g · d-1). When the dose was adjusted to 2.5 g · d-1, CFR Only reached 83.95% and 73.10%. CFR up to 82.81% at 0.8 g · d-1 in patients with moderate renal injury, and CFR up to 73.10 at 0.8 ~ 2.5 g · d-1 in the treatment of Enterococcus faecium % ~ 86.84%. Severe renal injury patients, treatment of Enterococcus faecium and Enterococcus faecalis infection, at 0.4g · d-1, the CFR up to 97.77% and 85.90%. Conclusion Monte Carlo simulation results show that the drug dosing regimen, supplementation and optimization of norvancomycin dosing regimen.