Han Yun, Zhu Jianping, Liu Jieqiong, Zheng Ying, Liang Gang, Yang Yi, Yu Lingyan, Yu Zhenwei, Han Gang
Research Center for Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People's Republic of China.
Infect Drug Resist. 2024 Jul 8;17:2823-2832. doi: 10.2147/IDR.S469313. eCollection 2024.
Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets.
This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR.
Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%T ≥ MIC (ceftazidime) and 50%T ≥ C (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%T ≥ MIC and 100%T ≥ C. Only continuous infusion at higher dosages achieved 100%T ≥ 4×MIC and 100%T ≥ C targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for , with the attainment rates vary across different regions.
The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.
近期研究表明延长输注时间对优化头孢他啶/阿维巴坦的治疗效果具有潜在益处，这表明当前的药代动力学/药效学（PK/PD）靶点可能并不充分，尤其是对于严重感染。本研究的目的是评估在应用更高的PK/PD靶点时，头孢他啶/阿维巴坦给药策略和输注持续时间的充分性。
本研究利用已发表的PK参数进行蒙特卡洛模拟。模拟了不同剂量，包括基于肾功能的推荐方案，并通过达标概率（PTA）和反应累积分数（CFR）进行评估。为头孢他啶和阿维巴坦设定了不同的PK/PD靶点。使用来自各种来源的MIC分布来计算CFR。
本研究设定了多个PK/PD靶点，所有推荐剂量均可轻松达到50%T≥MIC（头孢他啶）和50%T≥C（阿维巴坦）的靶点。然而，对于肾功能正常和肾功能增强的严重感染患者，按推荐剂量（2000mg/500mg，每8小时一次）给药时，输注持续时间需要延长至3小时和4小时，以达到100%T≥MIC和100%T≥C的靶点。只有更高剂量的持续输注对所有当前推荐方案都能达到100%T≥4×MIC和100%T≥C的靶点。根据不同的MIC分布，对[此处原文缺失相关内容]需要更高的浓度，不同地区的达标率有所不同。
目前推荐的头孢他啶/阿维巴坦给药方案对严重感染患者并不充分，建议持续输注。
