Zou Dongna, Yao Guangyue, Shen Chengwu, Ji Jinru, Ying Chaoqun, Wang Peipei, Liu Zhiying, Wang Jun, Jin Yan, Xiao Yonghong
Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Cancer Therapy and Research Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Front Microbiol. 2021 Nov 25;12:738812. doi: 10.3389/fmicb.2021.738812. eCollection 2021.
The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further. Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE. For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 μg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 μg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 μg/mL, 8 μg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE. This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.
本研究旨在预测和评估三种抗菌药物用于治疗中国成人耐碳青霉烯类肠杆菌科细菌（CRE）血流感染（BSI）的效果，以便进一步优化临床给药方案。血液分离株的抗菌药物敏感性数据来自中国血液细菌耐药性调查协作系统。进行蒙特卡洛模拟以估计替加环素、多粘菌素B和头孢他啶/阿维巴坦针对CRE的目标达成概率（PTA）和累积反应分数（CFR）。对于PTA结果，当最低抑菌浓度（MIC）分别为0.25、0.5和0.5μg/mL时，每12小时给予50mg、每12小时给予75mg和每12小时给予100mg的替加环素的PTA均>90%；对于所有测试方案给药的多粘菌素B，当CRE的MIC为1μg/mL时，PTA>90%；当CRE的MIC分别为4μg/mL、8μg/mL时，每8小时给予1.25g、每8小时给予2.5g的头孢他啶/阿维巴坦的PTA>90%。至于三种抗菌药物的CFR值，头孢他啶/阿维巴坦的CFR值最低。头孢他啶/阿维巴坦的最高CFR值为77.42%。对于替加环素和头孢他啶/阿维巴坦，随着模拟方案每日给药量增加，CFR值均增加；替加环素的最高CFR值为91.88%。对于多粘菌素B，每12小时1.5mg/kg的最大剂量可提供针对CRE的最高CFR值（82.69%）。本研究表明，应综合考虑MIC测量和个体化治疗以实现最佳药物暴露。特别是，基于当地抗菌药物耐药性数据的药代动力学和药效学建模可为临床医生进行BSIs经验性抗生素治疗给药提供有价值的指导。
