Kang Yixin, Cui Junchang
Department of Respiratory Diseases, The first Medical Center, Chinese People's Liberation Army General Hospital, China.
Jpn J Infect Dis. 2023 Jan 24;76(1):1-6. doi: 10.7883/yoken.JJID.2022.289. Epub 2022 Jul 29.
The objective of this pharmacokinetic (PK)/pharmacodynamic (PD) analysis was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) for the treatment of pulmonary infections by extensively drug-resistant (XDR) Pseudomonas aeruginosa using optimized two-step administration therapy (OTAT) and traditional infusion (TI). We used Monte Carlo simulations (MCS) to integrate PK parameters with PD parameters to assess the adequacy of CZA dosing in critically ill patients with XDR P. aeruginosa pulmonary infections. Dosing models were as follows: 2.5 g q8h, 2.5 g q6h, 4 g q8h, 4 g q6h, 1.25 g q8h, 1.25 g q6h, and 0.94 g q12h. MCS showed that the cumulative fraction of response of all dosing regimens of OTAT was higher than 90%. The probability of target attainment of all dosing regimens of OTAT at MICs (minimal inhibitory concentrations) between 16 mg/L and 32 mg/L was higher than that of TI. Based on these models, PK/PD goals were met with OTAT regimens, even with high MICs (>16 mg/L) compared to traditional infusion (TI) intervals. Thus, this study indicates that OTAT with sufficient PK exposure could improve the efficacy of CZA in critically ill patients with XDR P. aeruginosa pulmonary infections.
本药代动力学（PK）/药效学（PD）分析的目的是，使用优化两步给药疗法（OTAT）和传统输注（TI），评估不同剂量方案的头孢他啶/阿维巴坦（CZA）治疗广泛耐药（XDR）铜绿假单胞菌肺部感染的疗效。我们使用蒙特卡洛模拟（MCS）将PK参数与PD参数整合，以评估XDR铜绿假单胞菌肺部感染重症患者CZA给药的充足性。给药模型如下：2.5 g每8小时一次、2.5 g每6小时一次、4 g每8小时一次、4 g每6小时一次、1.25 g每8小时一次、1.25 g每6小时一次，以及0.94 g每12小时一次。MCS显示，OTAT所有给药方案的累积反应分数均高于90%。OTAT所有给药方案在最低抑菌浓度（MIC）为16 mg/L至32 mg/L时的达标概率高于TI。基于这些模型，即使与传统输注（TI）间隔相比MIC较高（>16 mg/L），OTAT方案也能实现PK/PD目标。因此，本研究表明，具有足够PK暴露的OTAT可提高CZA治疗XDR铜绿假单胞菌肺部感染重症患者的疗效。
