Newborn baby being held
Credit: Genomics England

Bacterial bloodstream infections in extremely preterm babies may originate from their gut microbiomes, research suggests.

Identical or nearly identical gut bacteria were found in more than half of the cases before a bloodstream infection was diagnosed, according to the study in Science Translational Medicine.

Numerous babies in the same neonatal intensive care unit (NICU) also carried the same or similar bloodstream infection strains, suggesting that these were shared in the hospital environment.

Antibiotic treatment appeared to promote the growth of opportunistic microbes already resident in the guts of these babies, with these pathogens going on to cause bacteremia and late-onset sepsis.

The researchers propose that rapid microbiome sequencing at the start of late-onset sepsis could help determine antibiotic use and treatments against the organism causing infection.

“Our study also suggests that an early look at the gut microbiome in preemies may allow us to identify those at high risk of dangerous bloodstream infections,” said senior researcher Gautam Dantas, PhD,  a professor of pathology and immunology at Washington University School of Medicine in St Louis.

Preterm infants in NICUs are particularly vulnerable to infection because of their immature organ systems, breach of cutaneous and mucosal barriers, and considerable exposure to antimicrobials.

However, treating newborns unnecessarily with antibiotics for culture-negative sepsis carries morbidity and mortality risks, including those from future episodes of culture-positive, late-onset sepsis and blood-stream infections.

Identifying at-risk infants could therefore help inform appropriate antibiotic treatment while also limiting its unnecessary use.

The researchers initially studied 550 previously published fecal metagenomes from 115 hospitalized newborns.

They then performed shotgun metagenomic sequencing on 462 stool samples from 19 preterm babies with bloodstream infections and 37 without such infections, together with whole-genome sequencing of isolates from the bloodstream infections.

Results showed that 58% of gut microbiomes prior to bloodstream infection, and 79% of gut microbiomes at any time, had the bloodstream isolate with fewer than 20 genomic substitutions.

Dantas et al. found that infants with bloodstream infections caused by Enterobacteriaceae were more likely than those with infections from other organisms to have had exposure to ampicillin, gentamicin, or vancomycin in the 10 days before bloodstream infection.

Bloodstream infection strain tracking within the gut microbiome identified sources of pathogens and strain sharing within the NICU.

“Our results can inform future risk prediction algorithms based on gut microbiome abundance of potential pathogens for hospitalized, preterm infants to anticipate and intervene on at-risk infants,” the researchers suggested.

They added:  “The possibility of performing rapid sequencing at the start of late-onset sepsis could also help inform antibiotic stewardship and direct more rapid, effective treatment of a causative organism.”

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