【摘要】 目的:根据抗菌药物PK/PD理论,采用蒙特卡罗模拟的手段,对肾功能不全患者万古霉素治疗肠球菌感染的给药方案进行优化。方法:收集已发表的万古霉素的药动学资料和我院万古霉素对粪肠球菌和屎肠球菌的MIC分布数据;设置AUC24h/MIC>400,利用Crystal Ball软件模拟出5 000个患者的PTA和CFR。结果:万古霉素能达到满意抗菌活性的最低剂量:对于肌酐清除率>80 mL.min-1的患者(A组),当MIC=0.5μg.mL-1时,给予万古霉素1 500 mg.d-1;当MIC=1μg.mL-1时,给予万古霉素2 500 mg.d-1。对于肌酐清除率在50～80 mL.min-1的患者,当MIC=0.5μg.mL-1时,给予万古霉素1 000 mg.d-1,当MIC=1μg.mL-1时,给予万古霉素2 000 mg.d-1。对于肌酐清除率在10～50 mL.min-1的患者,只有在MIC=0.5μg.mL-1时给予750 mg.d-1,才能达到满意的抗菌活性。结论:蒙特卡罗模拟法把药动学和药效学结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,这样获得的给药方案将更合理,也更能提高临床治疗效果。更多还原

【Abstract】 OBJECTIVE According to the antibiotic PK/PD theory,and adopting Monte Carlo simulation method,to optimize the drug administration scheme in patients with renal insufficiency treated with vancomycin against enterococcus infection.METHODS The published pharmacokinetic data of vancomycin and the MIC data distribution in our hospital about vancomycin against Enterococcus faecalis and Enterococcus faecium were collected;setting AUC24 h/MIC>400,and using Crystal Ball software to simulate 5 000 patients with PTA and CFR.RESULTS Vancomycin could achieve satisfactory antibacterial activity at the lowest dose: for the patients with creatinine clearance > 80 mL·min-1(group A),when MIC=0.5 μg·mL-1,giving vancomycin 1 500 mg·d-1;when MIC=1 μg·mL-1,giving vancomycin 2 500 mg·d-1.For the patients with creatinine clearance rate in 50~80 mL·min-1,when MIC=0.5 μg·mL-1,vancomycin was given with 1 000 mg;when MIC=1 μg·mL-1,giving vancomycin 2 000 mg·d-1.For the patients with creatinine clearance rate in 10~50 mL·min-1,only in MIC=0.5 μg·mL-1 vancomycin given at the dose of 750 mg·d-1 could achieve a satisfactory antibacterial activity.CONCLUSION The Monte Carlo simulation method combined pharmacokinetics with pharmacodynamics,considering not only the difference of drug disposition in different individuals,but also the difference in drug resistance of pathogenic bacteria,so the acquired dosing regimens will be more reasonable,and can be used for improving the effect of clinical treatment.更多还原