Recommended Antibiotic Dosage Regimens in Critically Ill Patients with Augmented Renal Clearance: A Systematic Review

Abstract

Purpose: Augmented renal clearance (ARC) is common in critically ill patients and may lead to subtherapeutic levels of antibiotics, thus influencing clinical outcomes and emergence of multidrug-resistant bacteria. The aim of this systematic review was to search the literature for recommendations concerning dosage adjustment for antibiotics administered to critically ill patients with ARC.

Methods: A search of three electronic databases (Pubmed, Embase and Cochrane) was conducted from inception until the end of March 2021, using terms related to: 1) pharmacokinetics/pharmacodynamics (PK/PD), 2) antibiotic, 3) ARC and 4) critically ill. Two reviewers searched for relevant data and included studies suggesting specific doses for critically ill patients with ARC.

Results: Forty-seven studies met the inclusion criteria. Dosage recommendations were found for 18 antibiotics. Differences were found in population characteristics, ARC definition, creatinine clearance (CL_CR) determination method, PK methodology and definition of PK/PD targets. Cut-off values for CL_CR ranged 120-240 mL/min; the most frequently employed method to define CL_CR was Cockcroft-Gault estimation; and 83% of studies used population PK models to predict dosing regimens. All antibiotics, except three, needed upward dosing and/or infusion modality adjustments to reach PK/PD targets.

Conclusion: Despite the lack of high-quality studies and high heterogeneity, incremental dosing adjustment of antibiotics was frequently needed for critically ill patients with ARC to achieve the desired PK/PD targets. More research is needed to enlarge the number of antibiotics with recommendations for ARC and to validate current suggestions based on mathematical models in a clinical scenario.

Keywords: Antibiotic; Augmented renal clearance; Critically ill; Dosing; Pharmacodynamics; Pharmacokinetics.