Efficacy and safety of short- vs. standard-course antibiotics for culture-negative neonatal sepsis: a systematic review and meta-analysis.

OBJECTIVES:To conduct a systematic review and meta-analysis of evidence from randomized controlled trials (RCTs) comparing a short course of antibiotics (2-4 days), to a standard course (5-7 days), for the treatment of culture-negative neonatal sepsis. METHODS:Relevant databases were searched for RCTs comparing short- vs. standard-course of antibiotics for culture-negative sepsis. The primary outcomes were mortality and treatment failure, defined as the reappearance of clinical signs suggestive of sepsis within 7 days of stoppage of antibiotics. Secondary outcomes included neurological impairment, duration of hospital stay, need for oxygen, respiratory support and double-volume exchange transfusion (DVET). RESULTS:Seven RCTs were included in the review with 729 neonates >30 weeks gestational age at birth. No mortality occurred in either of the groups (2 studies; 276 neonates). Treatment failure rates were similar in the short- and standard-course antibiotic groups [7 studies; 729 neonates; risk ratio (RR) = 1.01; 95% confidence interval (CI), 0.55 to 1.86; very low certainty]. The short course of antibiotics resulted in a shorter hospital stay [3 studies; 293 neonates; mean difference (MD), -2.46 days; 95% CI, -3.16 to -1.75]. There was no difference in the need for oxygen supplementation (2 studies; 258 neonates; RR, 1.40; 95% CI, 0.40 to 4.91), any respiratory support (2 studies; 258 neonates; RR, 1.04; 95% CI, 0.92 to 1.17) or DVET (2 studies; 258 neonates; RR, 1.29; 95% CI, 0.56 to 2.95). CONCLUSION:Very-low certainty evidence suggests that a short antibiotic course, compared to a standard course, does not affect treatment failure rates in culture-negative neonatal sepsis. There is a need for well-designed RCTs powered enough to assess critical outcomes such as mortality and neurological sequelae to generate stronger evidence and inform guidelines. PROSPERO REGISTRATION NUMBER:CRD42023437199.