Adequacy of the Dosing and Infusion Time of Ceftazidime/Avibactam for the Treatment of Gram-Negative Bacterial Infections: A PK/PD Simulation Study

IF 2.9 3区医学 Q2 INFECTIOUS DISEASES

Infection and Drug Resistance Pub Date : 2024-07-08 DOI:10.2147/idr.s469313

Yun Han, Jianping Zhu, Jieqiong Liu, Ying Zheng, Gang Liang, Yi Yang, Lingyan Yu, Zhenwei Yu, Gang Han

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引用次数: 0

Abstract

Introduction: 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.
Methods: 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.
Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ C_{T=1.0 mg/L} (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%fT ≥ MIC and 100%fT ≥ C_{T=1.0 mg/L}. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ C_{T=4.0 mg/L} targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions.
Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.

Keywords: ceftazidime, avibactam, pharmacokinetic/pharmacodynamic, probability of target attainment

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头孢他啶/阿维巴坦治疗革兰氏阴性菌感染的剂量和输注时间的适当性：一项 PK/PD 模拟研究

引言最近的研究表明，延长输注时间可能有利于优化头孢他啶/阿维巴坦的疗效，这表明目前的药代动力学/药效学（PK/PD）目标可能不够充分，尤其是对于重症感染。本研究旨在评估头孢他啶/阿维巴坦在应用更高的PK/PD目标时，其剂量策略和输注持续时间是否足够：本研究利用已公布的 PK 参数进行蒙特卡罗模拟。模拟了不同的剂量，包括基于肾功能的推荐方案，并通过达标概率（PTA）和累积应答分数（CFR）进行了评估。为头孢他啶和阿维菌素设定了不同的 PK/PD 目标。不同来源的 MIC 分布用于计算 CFR：本研究设定了多个PK/PD目标，所有推荐剂量均可轻松达到50%fT≥MIC（头孢他啶）和50%fT≥CT=1.0 mg/L（阿维巴坦）的目标。然而，对于肾功能正常且肾清除率增高的重症感染患者，在推荐剂量（2000 毫克/500 毫克，每 8 小时一次）下，输注时间需延长至 3 小时和 4 小时，以达到 100%fT ≥ MIC 和 100%fT ≥ CT=1.0 毫克/升的目标。在目前推荐的所有治疗方案中，只有持续输注更高的剂量才能达到100%fT≥4×MIC和100%fT≥CT=4.0 mg/L的目标。根据不同的 MIC 分布，铜绿假单胞菌需要更高的浓度，不同地区的达标率也不同：关键词：头孢他啶；阿维巴坦；药动学/药效学；达标概率

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来源期刊

Infection and Drug Resistance Medicine-Pharmacology (medical)

CiteScore

5.60

自引率

7.70%

发文量

826

审稿时长

16 weeks

期刊介绍： About Journal Editors Peer Reviewers Articles Article Publishing Charges Aims and Scope Call For Papers ISSN: 1178-6973 Editor-in-Chief: Professor Suresh Antony An international, peer-reviewed, open access journal that focuses on the optimal treatment of infection (bacterial, fungal and viral) and the development and institution of preventative strategies to minimize the development and spread of resistance.

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