Prolonged versus intermittent β-lactam infusion in sepsis: a systematic review and meta-analysis of randomized controlled trials

Background The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged β-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent β-lactam infusion in adult patients with sepsis. Methods We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent β-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905). Results We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72–0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03–1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98–1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64–1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68–0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72–0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38–0.98; P = 0.04). Conclusions Compared to intermittent infusion, prolonged infusion of β-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events.