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

ABSTRACT

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.

Prolonged antibiotic usage has been associated with increased mortality and morbidity in neonates. The standard practice in culture-negative neonatal sepsis has been to administer antibiotics for 5­7 days, based on expert consensus. In this systematic review, a short course of antibiotics (2­4 days), in comparison to a standard course (5­7 days), did not affect the treatment failure rates in culture-negative neonatal sepsis. However, the certainty of evidence was too low to make robust conclusions. There is a need for well-designed large trials to generate stronger evidence and inform guidelines.