Early discontinuation of empirical antibiotics versus extended treatment in children with cancer and high-risk febrile neutropenia in Denmark: an open-label, randomised controlled trial.

Summary

In a multicentre RCT of 88 febrile episodes in children with cancer and high-risk neutropenia, early discontinuation of IV antibiotics reduced mean antibiotic days by 4.0 without increasing serious adverse events or deaths. Findings support stewardship strategies using clinical stability and defervescence rather than neutrophil recovery to guide antibiotic duration.

Key Findings

• Early discontinuation reduced mean antibiotic exposure from 13.5 to 8.1 days (difference −4.0 days; p=0.0002).
• Serious adverse events were similar between groups (22% vs 21%); no deaths occurred.
• Open-label, multicentre design in three pediatric hemato-oncology centers with intention-to-treat analysis.

Clinical Implications

Clinicians managing pediatric high-risk febrile neutropenia can consider early discontinuation of IV antibiotics upon clinical stability and defervescence, independent of ANC recovery, with close follow-up.

Limitations

• Open-label design may introduce performance bias
• Sample size limits power to detect rare adverse outcomes

Future Directions

Larger pragmatic RCTs and implementation studies to validate safety across diverse settings, and to assess effects on resistance, microbiome, and long-term outcomes.