Shorter or biomarker-guided antibiotic durations for common serious neonatal infections: a collection of non-inferiority meta-analyses.

Summary

Across 26 RCTs, 7–10-day antibiotic courses were noninferior to longer durations for culture-positive neonatal sepsis on mortality and relapse thresholds. Biomarker-guided durations were also noninferior for mortality and relapses. Evidence certainty varied (low to very low for several outcomes), supporting stewardship with careful implementation.

Key Findings

• In culture-positive neonatal sepsis (7 RCTs), 7–10-day courses were noninferior to longer courses for 28-day and in-hospital mortality (upper 95% CI within MCIDs).
• Noninferiority thresholds were met for culture-positive relapse (+0.75% vs 3% MCID) and culture-negative relapse (+4.7% vs 5% MCID).
• Biomarker-guided antibiotic durations (5 RCTs) were noninferior to standard durations for mortality and relapses.

Clinical Implications

Clinicians can consider 7–10-day courses for culture-positive neonatal sepsis and biomarker-guided stopping strategies, potentially reducing exposure and resistance while maintaining outcomes.

Limitations

• Certainty of evidence often low to very low for some outcomes; heterogeneity across infections and settings
• Abstract indicates incomplete data for some endpoints (e.g., truncated results for culture-negative sepsis)

Future Directions

High-quality, multicenter RCTs with standardized definitions and biomarker algorithms; implementation studies to assess safety, resistance, and cost impacts.