Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis

BACKGROUND: Paediatric patients are often exposed to subtherapeutic levels or treatment failure of β-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as ≥3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as ≤60 min) of β-lactams in patients <21 years of age. METHODS: A systematic review and meta-analysis was conducted to compare EI and continuous infusion with SI of β-lactams in children. A systematic search was performed in MEDLINE (via PubMed), Embase, CENTRAL, and Scopus databases for randomised controlled trials (RCTs) and observational studies published from database inception up to August 22, 2023. Any comparative study concerned with mortality, clinical efficacy, adverse events, or plasma concentrations of β-lactams for any infection was eligible. Case reports, case series, and patients aged >21 years were excluded. Odds ratios (OR) and median differences with 95% confidence intervals (CI) were calculated using a random-effects model. Risk of bias (ROB) was assessed using ROB2 and ROBINS-I tools. The protocol was registered with PROSPERO, CRD42022375397. FINDINGS: In total, 19,980 articles were screened, out of which 19 studies (4195 patients) were included in the meta-analysis. EI administration was associated with a significantly lower all-cause mortality in both RCTs and non-RCTs [OR 0.74; CI 0.55–0.99; I(2) = 0%; CI 0–58%]. Early microbiological eradication was higher with EI [OR 3.18; CI 2.24–4.51; I(2) = 0%; CI 0–90%], but the clinical cure did not differ significantly between the two groups [OR 1.20; CI 0.17–8.71; I(2) = 79%; CI 32–93%]. Achieving the optimal plasma level (50–100% fT > MIC) appeared favourable in the EI group compared to the SI. No significant differences were observed in the adverse events. The overall ROB was high because of the small sample sizes and clinically heterogeneous populations. INTERPRETATION: Our findings suggest that extended infusion of β-lactams was associated with lower mortality and increased microbiological eradication and was considered safe compared to short-term infusion. FUNDING: None.