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病例报告:老年患者连续性肾脏替代治疗期间及治疗后头孢他啶和阿维巴坦的药代动力学及其与中枢神经系统不良反应的关联

Case Report: Pharmacokinetics of ceftazidime and avibactam during and after CRRT in an elderly patient and their associations with CNS adverse effects.

作者信息

Huang Haiying, Han Yun, Wu Yinshan, Guo Feng, Yu Zhenwei

机构信息

Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Research Center of Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Science, Zhejiang University, Hangzhou, China.

出版信息

Front Pharmacol. 2025 May 21;16:1569715. doi: 10.3389/fphar.2025.1569715. eCollection 2025.

DOI:10.3389/fphar.2025.1569715
PMID:40469986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12133543/
Abstract

Ceftazidime/avibactam is effective for treating infections caused by multidrug-resistant gram-negative bacteria and is widely used. The pharmacokinetic data of ceftazidime and avibactam in patients receiving continuous renal replacement therapy (CRRT) are limited. It is challenging to dose ceftazidime/avibactam, as excessive exposure is associated with central nervous system (CNS) adverse events, especially in older patients. This case reported the pharmacokinetic parameters of ceftazidime and avibactam (1.25 g every 8 h) in an elderly patient during and after CRRT (continuous veno venous hemofiltration mode), which were estimated based on a first-order elimination equation and a two-point sampling strategy. CRRT accounted for 84.9% of the total clearance rate of ceftazidime and 77.1% of the total clearance rate of avibactam. Excessive drug exposure (plasma concentrations of ceftazidime and avibactam were 109 and 20.6 mg/L, respectively) 5 days after discontinuation of CRRT resulted in adverse CNS reactions, which manifested as involuntary convulsions and abnormal brain discharge. This case study provides pharmacokinetic data of ceftazidime and avibactam in patient during and after CRRT and information about the possible relationship between concentrations and CNS adverse reactions.

摘要

头孢他啶/阿维巴坦对治疗多重耐药革兰氏阴性菌引起的感染有效且应用广泛。接受持续肾脏替代治疗(CRRT)患者的头孢他啶和阿维巴坦的药代动力学数据有限。头孢他啶/阿维巴坦的给药具有挑战性,因为暴露过多与中枢神经系统(CNS)不良事件相关,尤其是在老年患者中。本病例报告了一名老年患者在CRRT期间及之后(持续静静脉血液滤过模式)头孢他啶和阿维巴坦(每8小时1.25 g)的药代动力学参数,这些参数是基于一级消除方程和两点采样策略估算得出的。CRRT分别占头孢他啶总清除率的84.9%和阿维巴坦总清除率的77.1%。CRRT停止5天后药物暴露过多(头孢他啶和阿维巴坦的血浆浓度分别为109和20.6 mg/L)导致CNS不良反应,表现为不自主抽搐和脑部放电异常。本病例研究提供了CRRT期间及之后患者头孢他啶和阿维巴坦的药代动力学数据以及浓度与CNS不良反应之间可能关系的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf00/12133543/5228d1fabc4d/fphar-16-1569715-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf00/12133543/5228d1fabc4d/fphar-16-1569715-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf00/12133543/5228d1fabc4d/fphar-16-1569715-g001.jpg

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本文引用的文献

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Front Pharmacol. 2024 Nov 27;15:1470350. doi: 10.3389/fphar.2024.1470350. eCollection 2024.
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Adequacy of the Dosing and Infusion Time of Ceftazidime/Avibactam for the Treatment of Gram-Negative Bacterial Infections: A PK/PD Simulation Study.
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Infect Drug Resist. 2024 Jul 8;17:2823-2832. doi: 10.2147/IDR.S469313. eCollection 2024.
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