[关键词]
[摘要]
目的 结合万古霉素及氨苄西林的药代动力学/药效动力学(PK/PD)模型,运用蒙特卡洛模拟2种药物不同给药方案对由屎肠球菌及粪肠球菌引起的细菌性尿路感染的治疗效果。方法 回顾性收集安徽中医药大学第二附属医院2024年1月—2025年12月通过VITEK2全自动微生物分析系统检测的细菌性尿路感染患者尿液标本中分离出的屎肠球菌及粪肠球菌的最小抑菌浓度(MIC),运用蒙特卡洛模拟法分别模拟氨苄西林和万古霉素共4种给药方案对“10 000名虚拟肠球菌致细菌性尿路感染患者”的临床疗效,其中氨苄西林以游离型药物浓度超过靶细菌的MIC的时间(f% T>MIC)>50%为靶值,万古霉素以药时曲线下面积(AUC)与细菌MIC的比值(AUC0~24 h/MIC,AUIC)≥400为靶标得到达标概率(PTA),并计算各方案抗感染成功为目标阈值的累计反应分数(CFR)。结果 共计分离出屎肠球菌、粪肠球菌分别114株与69株,其中氨苄西林钠给药方案1(每次3 g,给药间隔6 h,简写为3g,q6h)对MIC为2、4、8 μg·mL-1的屎肠球菌及粪肠球菌的PTA>90%,给药方案2(每次3 g,给药间隔8 h,简写为3g,q8h)对MIC为2 μg·mL-1的屎肠球菌及粪肠球菌的PTA>90%,;万古霉素给药方案1(每天2 g)对MIC为0.5 μg·mL-1的屎肠球菌及粪肠球菌的PTA>90%,给药方案2(每天3 g)对MIC为0.5、1.0 μg·mL-1的屎肠球菌及粪肠球菌的PTA>90%; 2种给药方案的氨苄西林钠对屎肠球菌的CFR均小于90%,每天3 g的万古霉素对屎肠球菌的CFR大于90%;给药方案3g,q6h的氨苄西林钠及2种万古霉素给药方案对粪肠球菌的CFR值大于90%。结论 对比这2种药物的4种给药方案,对于粪肠球菌导致的尿路感染,可以使用3g,q6h的氨苄西林钠及每天2 g的万古霉素进行治疗。对于屎肠球菌感染可以使用每天3 g的万古霉素进行治疗,其他治疗方案可能会导致治疗失败,但同时需要加强患者肾功能的检测,减少不良反应带来的危害。
[Key word]
[Abstract]
Objective To provide reference for clinical individual medication of vancomycin and ampicillin by combining PK/PD and Monte Carlo simulation. Methods The minimum inhibitory concentration (MIC) of Enterococcus faecium and Enterococcus faecalis isolated from urine samples of patients with bacterial urinary tract infection detected by VITEK2 Compact automatic microbial analysis system in the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2024 to December 2025 was retrospectively collected, Monte Carlo simulation method was used to simulate the clinical efficacy of ampicillin and vancomycin and ampicillin on “10 000 patients with bacterial urinary tract infection caused by Enterococcus”. Among them, ampicillin targeted (f%T > MIC) > 50%, and vancomycin targeted AUIC ≥ 400 to obtain the probability of target attachment (PTA), And calculate the cumulative fraction of response (CFR) for the target threshold of successful anti infection in each protocol. Results A total of 69 strains of E. faecium and 114 strains of E. faecalis were isolated, of which the dosage regimen was 3 g every time, and the MIC of ampicillin sodium and once every 8 h (hereinafter referred to as 3g, q8h, the same below) was 2, 4, 8 μg·mL-1 for PTA > 90% of E. faecium and E. faecalis and the MIC of PTA > 90% of the dosage regimen (3g, q6h) was 8 8 μg·mL-1; The MIC of vancomycin (2 g/d) for E. faecium and E. faecalis (PTA > 90%) was 0.5 μg·mL-1, and the MIC of 3 g·d-1 (PTA > 90%) is 0.5, 1.0 μg·mL-1; The CFR of ampicillin sodium against Enterococcus was less than 90%, and the CFR of 3 g·d-1 vancomycin against Enterococcus was more than 90% in the two administration schemes; The CFR value of ampicillin sodium and at 3g, q6h and vancomycin at 2 g·d-1 for Enterococcus was more than 90%. Conclusion Compared with the four administration schemes of the two drugs, ampicillin sodium and (3 g q6h) and Vancomycin (2 g·d-1) can be used for the treatment of urinary tract infection caused by fecal intestinal bulb. Enterococcus infection can be treated with 3 g·d-1 Vancomycin. Other treatment schemes may lead to failure, but at the same time, it is necessary to strengthen the detection of renal function of patients to reduce the harm caused by adverse reactions.
[中图分类号]
R983
[基金项目]
安徽省高校优秀青年教师项目(YQYB2024030);安徽省高校自然科学研究重点项目(2023AH050866);安徽中医药大学第二附属医院“杏林英才”培育计划项目(2023-0500-48-46)