How to perform pharmacokinetic research of antimicrobial drugs in critically ill patients undergoing continuous renal replacement therapy: a scoping review of all relevant pharmacokinetic factors

Abstract

Background: Critically ill patients in the intensive care unit represent a highly heterogeneous population with large variations in the pharmacokinetics (PK) of antimicrobials (antibiotics, antifungals, and antiviral agents), complicating optimal dosing strategies. This becomes even more complex in those receiving continuous renal replacement therapy (CRRT), because CRRT significantly alters drug clearance. Nonetheless, many PK studies exclude patients undergoing CRRT and existing studies often suffer from methodological limitations and small sample sizes, reducing their generalizability. Accordingly, there remains a critical gap in robust, evidence-based dosing guidelines for antimicrobials in intensive care unit patients on CRRT, despite the clear clinical need.

Objectives: To conduct a scoping review of the literature on factors affecting the PK of antimicrobials in critically ill patients undergoing CRRT, provide practical recommendations, and develop a CRRT-PK checklist for designing and conducting PK research in this patient group.

Methods: Embase, Medline, and Cochrane databases, and the reference lists of relevant publications were searched from database inception to 24 June 2025. Data were extracted independently by two reviewers (AW and TJLS) and disagreements were resolved through discussion until consensus was reached. No quality appraisal was performed. Extracted data were synthesized descriptively, grouped by the type of influencing factor (CRRT-, patient-, or drug-related).

Results: Of 811 articles identified in the search strategy, a total of 96 articles were included in the review. All relevant CRRT-, patient-, and drug-related factors that may influence the PK of antimicrobials are discussed. Moreover, we provided practical considerations and a CRRT-PK checklist for an appropriate study design and output.

Conclusions: This review, along with the checklist, can form the foundation for designing and conducting high-quality PK studies in critically ill patients undergoing CRRT. By improving the consistency and reproducibility of future studies, this is the first step towards robust, evidence-based dosing guidelines for antimicrobials in critically ill patients undergoing CRRT.

Keywords: Antibiotics; Antifungal agents; Antimicrobial drugs; Antiviral agents; Continuous renal replacement therapy; Critically ill patients; ICU; Pharmacokinetics; Study design; Therapeutic drug monitoring.