Individualised duration of antibiotic treatment in culture-negative early-onset sepsis in late-preterm and term-born neonates in Denmark (DURATION): a multicentre, open-label, randomised, controlled, non-inferiority trial.

Summary

In a nationwide multicentre non-inferiority RCT of 493 neonates with culture-negative early-onset sepsis, a clinically guided individualized strategy safely reduced antibiotic duration to a median of 3 days and was non-inferior to standard 5–7 day therapy regarding infection-related readmissions. Trial registration NCT05329701.

Key Findings

• Individualized strategy met non-inferiority for infection-related readmission (risk difference 0.4%, 95% CI −1.5 to 2.6).
• Median antibiotic duration was reduced to 3 days in the individualized group versus 5–7 days standard care.
• Randomized 493 neonates across multiple centers; initiation of therapy occurred at ~22.5–24.5 hours after birth.

Clinical Implications

For late-preterm and term neonates with probable culture-negative EOS, consider CRP- and clinical trajectory-guided early discontinuation after 24 hours of stability to reduce antibiotic exposure.

Limitations

• Open-label design may introduce performance bias.
• Findings apply to culture-negative EOS in late-preterm/term infants; not generalizable to culture-positive cases or very preterm infants.

Future Directions

Evaluate implementation in diverse health systems, refine biomarker thresholds, and test applicability in very preterm infants and culture-positive EOS.