Prolonged Versus Intermittent Beta-Lactam Antibiotic Infusions in Paediatric Critical Care: A Systematic Review and Meta-Analysis

Abstract

Objective: In paediatric intensive care units (PICUs), beta-lactam antibiotic administration is often suboptimal, placing critically ill children at risk. We aimed to investigate the mortality, PICU length of stay, and pharmacokinetic/pharmacodynamic (PK/PD) benefits of prolonged beta-lactam infusions in PICU compared to intermittent infusions. Methods: A systematic review was conducted to identify studies investigating prolonged infusions compared to intermittent infusions. Studies were sourced from a previously published review and a systematic search of MEDLINE, Cochrane, Embase and Web of Science databases. Case reports, case series, systematic reviews and non-English language reports were excluded (PROSPERO CRD 42022375397). A meta-analysis with odds ratios (OR) and 95% confidence intervals (CIs) was conducted. When insufficient data were available, a descriptive analysis was undertaken. Risk of bias was assessed using the Robins-I tool. Results: In total, 566 studies were screened, of which 10 studies were included in the systematic review. All studies were observational, with sample sizes from 21 to 174 PICU patients (median 76; IQR 33–156). There was no reduction in mortality (N = 6 studies; OR 0.60; 95% CI 0.24, 1.51; I2 = 40%) in the prolonged infusion group compared to the intermittent group. There was insufficient data to perform further meta-analyses. The risk of bias was high and the overall quality of evidence was low. Conclusions: Available studies on prolonged infusions of beta lactams in PICU patients are limited and of low quality. Further research is needed to assess for clinical benefits associated with prolonged beta-lactam infusions for treatment of severe infection.