Prolonged infusion of β-lactam antibiotics decreases short-term mortality in critically ill patients: a meta-analysis and trial sequential analysis from randomized control trials

The aim was to ascertain the clinical efficacy of prolonged infusion of β-lactam antibiotics in critically ill patients and provide additional evidence. This meta-analysis was prospectively registered on PROSPERO database (CRD42024614894). We searched PubMed, Web of Science, Scopus and Clinical Trials.gov to identify eligible randomized control trials (RCTs) for conducting a meta-analysis and trial sequential analysis (TSA) comparing mortality between prolonged vs intermittent infusion of β-lactam antibiotics in adult critically ill patients. Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) was used to evaluate the certainty of evidence for all outcomes. 24 RCTs involving 9558 adult critically ill patients were finally included in this meta-analysis. Compared with intermittent infusion of β-lactam antibiotics, the pooled results demonstrated that prolonged infusion was associated with lower short-term mortality (OR, 0.87; 0.79 - 0.95; high certainty), but not 90-day mortality statistically (OR, 0.91; 0.83 - 1.01; moderate certainty), which was supported by TSA. Regression analysis found no significant factors affecting short-term mortality. For other outcomes, prolonged infusion could significantly improve clinical cure (OR, 1.31; 1.20 - 1.42; low certainty) and microbiological eradication (OR, 2.29; 1.61 - 3.25; moderate certainty) . Despite no benefit in 90-day mortality statistically, prolonged infusion of β-lactam antibiotics was associated with significant benefits in short-term mortality, clinical cure and microbiological eradication. TSA supported the short-term survival benefit of prolonged infusion in critically ill patients.