蒙特卡洛模拟评价和优化鲍曼不动杆菌血流感染给药方案

目的 应用蒙特卡洛模拟研究头孢哌酮/舒巴坦、替加环素和多黏菌素B治疗鲍曼不动杆菌血流感染的疗效，预测和评价不同抗菌药物的抗菌效果，进而优化临床给药方案。方法 借助全国血流感染细菌耐药监测联盟(BRICS)平台收集2018—2019年血流感染来源的鲍曼不动杆菌514株，使用文献公开发表的头孢哌酮/舒巴坦、替加环素和多黏菌素B的药动学参数，基于药动学/药效学(PK/PD)理论利用蒙特卡洛模拟法，计算不同给药方案在各特定的MIC值获得的目标概率，即达标概率(PTA)和累积反应分数(CFR)，以PTA或CFR≥90%作为临床疗效评价的指标。结果 治疗鲍曼不动杆菌引起的血流感染，头孢哌酮/舒巴坦给药方案4.5 g q6 h在最低抑菌浓度(MIC)≤1 mg/L时，可获得大于或接近90%的目标PTA值，临床分离菌的CFR值为21.53%。替加环素推荐剂量(50 mg q12 h)，在MIC≤0.25 mg/L时，可获得大于90%的目标PTA值，100 mg q12 h的给药方案对临床菌株的CFR值为81.04%。多黏菌素B 1.25 mg/kg 1h输注q12 h给药方案，可使MIC≤1 mg/L...

Use of Monte Carlo simulation to estimate and optimize therapeutic regimens of bloodstream infections caused by Acinetobacter baumannii

Abstract Objective To evaluate the efficacy of cefoperazone/sulbactam, tigecycline, and polymyxin B in thetreatment of bloodstream infections caused by Acinetobacter baumannii by Monte Carlo simulation, and to predictand evaluate the antibacterial effects of different antibiotics, so as to optimize the clinical administration scheme.Methods A total of 514 A. baumannii strains isolated from bloodstream infections from 2018 to 2019 were collectedwith the help of BRICS platform. The target probability (PTA) and cumulative response score (CFR) of differentdosage regimens at each specific MIC value were calculated using Monte Carlo simulation based on the publishedpharmacokinetic parameters of cefoperazone/sulbactam, tigecycline and polymyxin B, and PK/PD theory. PTA orCFR≥90% was used as the evaluation index of clinical efficacy. Results In the treatments of bloodstream infectionscaused by A. baumannii, cefoperazone/sulbactam (2:1) 4.5 g q6 h achieved more than or close to 90% PTA withMIC≤1 mg/L, and the CFR value was 21.53%. Using the recommended dose of tigecycline (50 mg, q12 h), whenMIC≤0.25 mg/L, more than 90% of the target PTA value could be obtained, and the CFR value of 100 mg q12 hwas 81.04%. The results showed that polymyxin B (1.25 mg/kg, 1 h infusion, q12 h) could make the PTA of bacteriawith MIC ≤ 1 mg/L reach more than 90%. The high dose polymyxin B [loading 2 mg/kg infused for 2 h, 2.5 mg/(kg·d)continuous infusion] could provide higher PTA (96.83%) and CFR (96.26%) when MIC was 2 mg/L. Conclusion Whencefoperazone/sulbactam is used in the treatment of A. baumannii infection, the high dose regimen should beconsidered. The higher resistance rate of A. baumannii to cefoperazone/sulbactam leads to lower CFR value. It maybe appropriate to use other antibiotics or combine cefoperazone/sulbactam with other antibacterial agents in clinicaltreatment to achieve better therapeutic outcomes. Tigecycline is recommended to be administered with 100 mg q12 h.Polymyxin B is recommended to be administered with loading 2.5 mg/kg infused for 2 h, 1.5 mg/kg infused for 1 h,q12 h or loading 2 mg/kg infused for 2 h, 2.5 mg/(kg·d) continuous infusion.