Comparative efficacy and safety of extended versus continuous infusion of beta-lactam antibiotics for severe infection: a network meta-analysis of randomized trials.

backgroundProlonged infusion (extended [EI, 2-4 h] or continuous [CI, 24 h] extended) of beta-lactam antibiotics is considered to have advantages for patients with severe infection compared with intermittent bolus (IB). However, the choice of EI and CI is unclear due to the lack of direct comparison. We aimed to compare the EI and CI of beta-lactams in patients with severe infections using a network meta-analysis method.

methodsWe systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, and Weipu Database for randomized controlled trials (RCTs) comparing EI, CI, or IB with beta-lactams in adults with severe infections. The primary outcome was all-cause mortality. A frequentist network meta-analysis with a random-effects model was performed. Risk of bias was assessed using the Cochrane RoB 2 tool.

findingsThirty-five RCTs (10,627 patients) were included. Risk of bias was moderate to high in most studies. For mortality, EI ranked highest (SUCRA 74.20%) with numerically lower rates versus IB (EI: OR 0.80, 95% CI 0.55-1.17; CI: OR 0.86, 95% CI 0.62-1.02). Both EI and CI significantly improved clinical cure rates versus IB (EI: OR 1.58, 95% CI 1.13-2.23; CI: OR 1.35, 95% CI 1.05-1.85), and EI ranked first (SUCRA 87.72%). For microbiological success, CI ranked highest (SUCRA 83.03%), followed by EI (SUCRA 42.98%) and IB (SUCRA 23.99%), but no significant difference was found. For hospital stay, EI was associated with a reduction of borderline statistical significance (MD -3.49 days, 95% CI -6.79 - -0.08), whereas CI did not show a significant reduction (MD 1.11 days, 95% CI -1.24 - 3.63), and EI ranked best (SUCRA 98.09%). No significant adverse event differences were observed. Subgroup analyses showed variable treatment rankings across categories, with no statistically significant subgroup effects.

conclusionIn patients with severe infections, both EI and CI improved clinical cure versus IB, whereas mortality did not differ significantly. Indirect evidence suggests EI may be more effective than CI in most outcomes except microbiological response. EI trended to shorten hospital stay but the difference was of borderline significance. Considering its practical feasibility, EI appears to be a favorable option based on current evidence. However, this finding is based on indirect evidence and requires confirmation in head-to-head trials. REGISTRATION: PROSPERO CRD420251242437.