The Ottawa Hospital, Ottawa, Ontario, Canada.
Montfort Hospital, Ottawa, Ontario, Canada.
Pharmacotherapy. 2023 Nov;43(11):1206-1220. doi: 10.1002/phar.2861. Epub 2023 Aug 28.
Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction were conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recommendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.
持续间歇性肾脏替代治疗（PIRRT）作为一种肾脏替代治疗模式在重症监护病房中越来越受欢迎，但与其他模式相比，其在抗菌药物清除率和剂量方面的指导相对较少。本系统评价的目的是：（1）确定并描述接受 PIRRT 的危重症成人中使用的相关抗菌药物的药代动力学（PK）；（2）评估支持这些数据的证据质量，（3）根据这些数据的综合提出剂量建议。设计并执行了多数据库搜索策略，以确定描述接受 PIRRT 的危重症成人中使用的抗菌药物 PK 的相关已发表证据。进行了质量评估、报告评估和相关数据提取，这些工作由两位研究者独立完成。除了证据质量外，研究者还评估了 PK/药效动力学（PD）结果的综合、研究作者的剂量建议以及纳入抗生素的物理化学特性，以制定剂量建议。39 项研究共纳入 452 例患者，符合纳入标准，并为接受 PIRRT 的危重症成人提供了 20 种抗菌药物的 PK 和/或 PD 数据。19 项研究同时描述了 PK 和 PD 结果。万古霉素（12 项研究，171 例患者）、美罗培南（7 项研究，84 例患者）和哌拉西林/他唑巴坦（5 项研究，56 例患者）是最常遇到的抗菌药物。20 种抗菌药物中有 7 种的证据质量被认为是强的，9 种抗菌药物有强有力的剂量建议。本系统评价更新并解决了该主题之前系统评价中存在的质量问题。尽管总体证据质量较低，但仍能对近一半的确定抗菌药物提出强有力的建议。许多抗菌药物仍存在知识空白，需要进行更高质量的研究（即评估 PD 目标达成情况的群体 PK 研究）来填补这些空白。
