Microbiome Signatures and Inflammatory Biomarkers in Culture-Negative Neonatal Sepsis

Area of Science:

• Neonatal Medicine
• Microbiology
• Immunology

Background:

• Antibiotic overuse is a concern for culture-negative sepsis (CN) in preterm infants.
• The causes of CN sepsis remain unclear, potentially involving unculturable microbes or inflammatory processes.

Purpose of the Study:

• To investigate the microbiome and cytokine profiles in preterm neonates with culture-positive sepsis (CP), CN sepsis, and asymptomatic controls (CO).
• To determine if microbial shifts or immune activation characterize CN sepsis and inform antibiotic stewardship.

Main Methods:

• Prospective study of 50 preterm neonates (CP, CN, CO groups).
• Evaluation of stool, skin, and blood microbiomes (bacterial, viral, fungal) and serum cytokine profiles.
• Statistical analyses including MaAsLin for microbial abundance and cytokine comparisons.

Main Results:

• No significant differences in microbiome diversity between CN and CO groups.
• Increased relative abundance of specific bacterial and fungal genera in stool and skin of CN infants compared to CO.
• No significant differences in virome or cytokine profiles between CN and CO groups; elevated cytokines in CP group.
• Adjusted analyses showed no significant differences in hospital stay or Bronchopulmonary Dysplasia (BPD) rates between CN and CO groups.

Conclusions:

• Culture-negative sepsis in preterm infants is associated with microbial shifts but not systemic immune activation.
• Findings support the discontinuation of antibiotics in preterm neonates with negative cultures.
• This approach may reduce antibiotic overuse and improve clinical outcomes.