Prolonged Beta-Lactam Infusions in Children: A Systematic Review and Meta-Analysis.

Objective: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections.
Study Design: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia.
Results: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis.
Conclusions: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies.
Competing Interests: Declaration of Competing Interest Amélie Marsot receives salary subsidy as chercheur boursier Junior 1 from the Fonds de Recherche Québec Santé (FRQS). Nadia Roumeliotis receives funding support as a clinician scientist from the Fonds de Recherche Québec Santé (FRQS) and the Canadian Institute for Health Research (CIHR) for projects unrelated to this work. The other authors declare no conflicts of interest.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)