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 this nationwide multicentre RCT, clinically guided individualized duration for culture-negative early-onset neonatal sepsis was noninferior to standard 5–7 days regarding infection-related readmission and reduced antibiotic exposure to a median of 3 days. The approach integrates serial clinical assessment and CRP trajectory.

Key Findings

• Randomized 493 neonates (246 individualized vs 247 standard) among 811 eligible across Denmark.
• Readmission due to bacterial infection: 1% (2/246) individualized vs <1% (1/247) standard; risk difference 0.4% (95% CI -1.5 to 2.6), meeting noninferiority.
• Total antibiotic duration reduced to a median of 3 days in the individualized arm versus 5–7 days standard.

Clinical Implications

Neonatal services can adopt individualized stop rules (no ongoing signs, CRP ≤30 mg/L and declining after 24 h) to reduce treatment duration to ~3 days in culture-negative EOS, with monitoring pathways to ensure safety.

Limitations

• Open-label design and very low event rates may limit precision around rare harms.
• Follow-up window for readmission is not detailed in the abstract, and generalizability to low-resource settings requires evaluation.

Future Directions

Validate in diverse health systems, refine biomarker thresholds and monitoring frequency, and assess impacts on microbiome, resistance, and long-term neurodevelopment.