药代动力学/药效学模型评估头孢他啶/阿维巴坦不同给药方案治疗产碳青霉烯酶肺炎克雷伯菌（KPC）肺炎克雷伯菌引起的肺炎的疗效：中国北方多中心研究。
Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China.
机构信息
Department of Respiratory Diseases, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Department of Respiratory Diseases, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China; Department of Respiratory Diseases, People's Hospital of Hainan District, Wuhai 016000, China.
出版信息
J Glob Antimicrob Resist. 2021 Dec;27:67-71. doi: 10.1016/j.jgar.2021.07.020. Epub 2021 Aug 21.
OBJECTIVES
The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections.
METHODS
A total of 70 KPC-Kp strains were isolated from sputum and bronchoalveolar lavage samples of patients with pulmonary infections in three hospitals in northern China from April 2015 to October 2015. Monte Carlo simulation (MCS) was performed using population pharmacokinetic parameters of CZA combined with the minimum inhibitory concentration (MIC) distributions gained from antimicrobial susceptibility testing to predict the efficacy of different dosing regimens. Various CZA dosing regimens were modelled using MCS.
RESULTS
The in vitro study showed potent activity of CZA against KPC-Kp strains with MIC values of 1/2 mg/L, with a susceptibility rate of 95.7%. The values of cumulative fraction of response (CFR) for bactericidal (50%fT>5 × MIC) target were as follows: for patients with creatinine clearance (CL) >51 mL/min, the CFR was 96.01% for 2.5 g CZA every 12 h (q12h) and 97.14% for 2.5 g CZA every 8 h (q8h); and for patients with moderate renal impairment (CL >30 to ≤50 mL/min), the CFR was 95.75% for 1.25 g CZA q12h and 97.09% for 1.25 g CZA q8h.
CONCLUSION
This study indicated that the recommended dose of CZA can provide adequate pharmacodynamic exposure for treating KPC-Kp pneumonia.
目的
本研究旨在评估不同剂量头孢他啶/阿维巴坦（CZA）给药方案治疗产肺炎克雷伯菌碳青霉烯酶（KPC-Kp）肺炎克雷伯菌（KPC-Kp）肺部感染患者的疗效。
方法
2015 年 4 月至 10 月，从中国北方三所医院的肺部感染患者的痰和支气管肺泡灌洗液样本中分离出 70 株 KPC-Kp 株。采用蒙特卡罗模拟（MCS），结合药敏试验获得的最小抑菌浓度（MIC）分布，对 CZA 的群体药代动力学参数进行模拟，预测不同剂量方案的疗效。使用 MCS 对各种 CZA 给药方案进行建模。
结果
体外研究表明，CZA 对 MIC 值为 1/2 mg/L 的 KPC-Kp 株具有强大的活性，敏感性率为 95.7%。杀菌（50%fT>5×MIC）目标累积反应分数（CFR）值如下：对于肌酐清除率（CL）>51 mL/min 的患者，2.5 g CZA 每 12 小时（q12h）给药的 CFR 为 96.01%，2.5 g CZA 每 8 小时（q8h）给药的 CFR 为 97.14%；对于中度肾功能不全（CL>30 至≤50 mL/min）患者，1.25 g CZA 每 12 小时（q12h）给药的 CFR 为 95.75%，1.25 g CZA 每 8 小时（q8h）给药的 CFR 为 97.09%。
结论
本研究表明，CZA 的推荐剂量可为治疗 KPC-Kp 肺炎提供足够的药效学暴露。
Zotero 插件