Abstract
BACKGROUND: Staphylococcus (S.) aureus remains a frequent pathogen for neonatal late-onset bloodstream infections (BSIs). The impact of colonization screening on BSI incidence is less understood. METHODS: We assessed the epidemiology of late-onset S. aureus BSI in two independent multicenter cohorts of preterm infants born at < 33 weeks' gestation, the German Neonatal Network (GNN, very low birth weight infants) and PRIMAL (infants with a gestational age 28-32 weeks). In the PRIMAL cohort, we determined S. aureus colonization in fecal samples by culture and shotgun metagenomic sequencing (metaG) during the first year of life. In addition, we integrated publicly available metaG data from preterm infant cohorts born at 23-34 weeks' gestation. RESULTS: Late-onset S. aureus BSI was noted in 1.5% (336/21491) in preterm infants in the GNN cohort and 0.5% (3/638) in the PRIMAL cohort, respectively. At day 30 of life, 7.6% (42/553) of fecal samples were positive for S. aureus, while available metaG data of corresponding samples revealed S. aureus positivity in 36.6% (159/434). Every 10-fold increase in S. aureus relative abundance (metaG) was associated with a 2.9-fold higher odds of S. aureus detection in blood culture. We also confirmed S. aureus detection in 22% (393/1782) of samples across several published cohorts of preterm infants by metaG, while 95 samples carried at least one Staphylococcus-specific virulence gene (SVG). CONCLUSION: Our study demonstrates that metagenomic quantification of pathobionts such as S. aureus in intestinal samples provides a stronger predictor of colonization than culture. Future prevention strategies should focus on promoting S. aureus colonization resistance through microbiome-informed approaches.