Pharmacokinetics of antimicrobials in pediatric patients treated with extracorporeal therapies- a systematic review

Abstract

AIMS & OBJECTIVES: Background: Optimal antimicrobial therapy relies on achieving effective concentrations for antimicrobials in critically ill patients. In critically ill adults on extracorporeal therapies such as extracorporeal membrane oxygenation (ECMO) and/or extracorporeal continuous renal replacement therapies(CRRT) suboptimal antimicrobial concentrations are commonly observed. In contrast, pharmacokinetic parameters measuring antimicrobial concentrations to assess antimicrobial effect are limited in pediatric patients on extracorporeal therapies. Objectives: To describe the studies in pediatric patients on antimicrobials requiring extracorporeal therapies, that report on pharmacokinetic parameters and associated pharmacodynamic targets. METHODS: Studies published between 1995 and 2019 were identified through systematic searches. Eligible studies included pharmacokinetic parameters, antimicrobials, extracorporeal therapy in pediatric cohort, including neonates. RESULTS: Twenty-two publications were identified, reporting antimicrobial pharmacokinetic parameters in pediatic patients on extracorporeal therapies. Thirteen ECMO studies incorporating three case studies, five prospective, and five retrospective studies were found. In addition, nine CRRT studies comprising of two case studies, four prospective, and three retrospective studies were identified. Six ECMO studies documented a direct comparison with pediatric patients not on ECMO. Pharmacokinetic parameters where derived from antimicrobial concentrations in blood, and volume of distribution, halflife and clearance were estimated. Most studies performed pharmacokinetics and pharmacodynamics analysis. Probability of achieving effective antimicrobial concentrations were investigated in three of the ECMO and two of the CRRT studies. Several studies proposed pharmacokinetic models from the data, however only one study prospectively evaluated the model. CONCLUSIONS: Given the limited availability of pharmacokinetic models for antimicrobials in extracorporeal therapies, improved antimicrobial pharmacokinetic models are required for pediatric patient care.L6347726342021-04-21 <br />