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应用蒙特卡罗模拟优化中国山东省肠杆菌科血流感染的抗生素选择。

Use of Monte Carlo simulation to optimize antibiotic selection for bloodstream infections caused by Enterobacteriaceae in Shandong Province, China.

机构信息

Medical Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, PR China.

Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, PR China.

出版信息

Diagn Microbiol Infect Dis. 2020 Jun;97(2):115039. doi: 10.1016/j.diagmicrobio.2020.115039. Epub 2020 Mar 12.

Abstract

The increasing rates of resistance to β-lactams have made it more challenging for clinicians to select appropriate antibiotic treatment for bloodstream infections (BSIs) caused by suspected Enterobacteriaceae. The objective of this analysis was to determine the optimal dosage regimens of β-lactams for treatment of BSIs based on analysis of 19,334 Enterobacteriaceae collected from blood specimens. Monte Carlo simulation using pharmacokinetic parameters of infected patients was performed to determine the probability of overall pharmacokinetic/pharmacodynamic (PK/PD) target attainment (OPTA). E. coli, K. pneumoniae, and E. cloacae were the 3 most common species. Nine of the 16 tested regimens had optimal OPTAs (>90%) for Enterobacteriaceae overall (meropenem 2g q8h, 3 h infusion; meropenem 2g q8h, 0.5h; meropenem 1g q8h, 0.5h; piperacillin/tazobactam 4.5g q8h, 3h; ceftazidime 2g q8h, 3h; imipenem 0.5g q6h, 0.5h; imipenem 1g q8h, 0.5h; piperacillin/tazobactam 3.375g q6h, 0.5h; ceftazidime 2g q8h, 0.5h). Four other regimens had sub-optimal OPTAs of 80 to 90% (piperacillin/tazobactam 4.5g q8h, 0.5h; ceftazidime 1g q8h, 0.5h; cefepime 2g q12h, 3h; and cefepime 2g q12h, 0.5h). Although there are high antibiotic MICs among Enterobacteriaceae in Shandong Province, carbapenem- , ceftazidime- and piperacillin/tazobactam- based regimens provide the optimal treatment.

摘要

β-内酰胺类药物耐药率不断上升,使得临床医生在为疑似肠杆菌科引起的血流感染(BSI)选择合适的抗生素治疗方案时面临更大挑战。本分析旨在根据从血样中收集的 19334 株肠杆菌科的分析,确定β-内酰胺类药物治疗 BSI 的最佳剂量方案。使用感染患者的药代动力学参数进行蒙特卡罗模拟,以确定总体药代动力学/药效学(PK/PD)目标达标概率(OPTA)。大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌是最常见的 3 个种。在测试的 16 种方案中,有 9 种方案对肠杆菌科的总体(美罗培南 2g q8h,3h 输注;美罗培南 2g q8h,0.5h;美罗培南 1g q8h,0.5h;哌拉西林/他唑巴坦 4.5g q8h,3h;头孢他啶 2g q8h,3h;亚胺培南 0.5g q6h,0.5h;亚胺培南 1g q8h,0.5h;哌拉西林/他唑巴坦 3.375g q6h,0.5h;头孢他啶 2g q8h,0.5h)具有最佳的 OPTAs(>90%)。其他 4 种方案的 OPTAs 为 80%至 90%(哌拉西林/他唑巴坦 4.5g q8h,0.5h;头孢他啶 1g q8h,0.5h;头孢吡肟 2g q12h,3h;头孢吡肟 2g q12h,0.5h)。尽管山东省肠杆菌科的抗生素 MIC 较高,但碳青霉烯类、头孢他啶和哌拉西林/他唑巴坦类药物治疗方案提供了最佳治疗方案。

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