Antimicrobial Stewardship Programs in Neonates: A Meta-Analysis

Abstract

BACKGROUND AND OBJECTIVES Neonatal sepsis is a significant contributor to mortality and morbidity; however, the uncontrolled use of antimicrobials is associated with significant adverse effects. Our objective with this article is to review the components of neonatal antimicrobial stewardship programs (ASP) and their effects on clinical outcomes, cost-effectiveness, and antimicrobial resistance. METHODS We selected randomized and nonrandomized trials and observational and quality improvement studies evaluating the impact of ASP with a cutoff date of May 22, 2023. The data sources for these studies included PubMed, Medline, Embase, Cochrane CENTRAL, Web of Science, and SCOPUS. Details of the ASP components and clinical outcomes were extracted into a predefined form. RESULTS Of the 4048 studies retrieved, 70 studies (44 cohort and 26 observational studies) of >350 000 neonates met the inclusion criteria. Moderate-certainty evidence reveals a significant reduction in antimicrobial initiation in NICU (pooled risk difference [RD] 19%; 95% confidence interval [CI] 14% to 24%; 21 studies, 27 075 infants) and combined NICU and postnatal ward settings (pooled RD 8%; 95% CI 6% to 10%; 12 studies, 358 317 infants), duration of antimicrobial agents therapy (pooled RD 20%; 95% CI 10% to 30%; 9 studies, 303 604 infants), length of therapy (pooled RD 1.82 days; 95% CI 1.09 to 2.56 days; 10 studies, 157 553 infants), and use of antimicrobial agents >5 days (pooled RD 9%; 95% CI 3% to 15%; 5 studies, 9412 infants). Low-certainty evidence reveals a reduction in economic burden and drug resistance, favorable sustainability metrices, without an increase in sepsis-related mortality or the reinitiation of antimicrobial agents. Studies had heterogeneity with significant variations in ASP interventions, population settings, and outcome definitions. CONCLUSIONS Moderate- to low-certainty evidence reveals that neonatal ASP interventions are associated with reduction in the initiation and duration of antimicrobial use, without an increase in adverse events.