A rapid time-resolved host gene expression signature predicts responses to antibiotic treatment in neonatal bacterial sepsis.

Summary

Time-resolved transcriptomics in microbiologically confirmed neonatal sepsis identified a treatment-responsive host gene signature that reverses within 24 hours of vancomycin initiation and tracks clinical improvement. Adaptive immune pathways changed unexpectedly fast, and signatures were conserved across pediatric and adult cohorts, enabling a prognostic measure and implicating early transient antimicrobial defense activation in neonatal sepsis.

Key Findings

• Identified a treatment-responsive host gene signature in neonatal sepsis with rapid reversal within 24 hours of antibiotic initiation.
• Adaptive immune system responses were among the fastest changing pathways.
• Signatures were conserved and reversible across pediatric and adult sepsis cohorts.
• A prognostic measure derived from treatment-responsive genes agreed with clinical assessments.
• Network modeling revealed an early transient rise in antimicrobial defense genes, suggesting impaired bactericidal responses in neonates.

Clinical Implications

Enables early (within 24 hours) assessment of antibiotic efficacy to support de-escalation and duration decisions, potentially reducing unnecessary exposure. Can be integrated into rapid transcriptomic diagnostics to guide personalized therapy and monitoring in neonatal sepsis.

Limitations

• Exact sample size and cohort diversity not specified in the abstract
• Antibiotic exposure centered on vancomycin may limit generalizability to other regimens; prospective clinical validation needed

Future Directions

Prospective multicenter validation of the signature’s predictive performance, expansion to diverse pathogens/antibiotics, integration into rapid point-of-care transcriptomic platforms, and interventional trials using signature-guided de-escalation.