Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections

Abstract

Background: Late-onset sepsis is a major problem in neonatology, but the habitat of the pathogens before bloodstream invasion occurs is not well established.

Methods: We examined prospectively collected stools from premature infants with sepsis to find pathogens that subsequently invaded their bloodstreams, and sought the same organisms in stools of infants without sepsis. Culture-based techniques were used to isolate stool bacteria that provisionally matched the bloodstream organisms, which were then genome sequenced to confirm or refute commonality.

Results: Of 11 children with late-onset neonatal bloodstream infections, 7 produced at least 1 stool that contained group B Streptococcus (GBS), Serratia marcescens, or Escherichia coli before their sepsis episode with provisionally matching organisms. Of 96 overlap comparison subjects without sepsis temporally associated with these cases, 4 were colonized with provisionally matching GBS or S. marcescens. Of 175 comparisons of stools from randomly selected infants without sepsis, 1 contained a GBS (this infant had also served as an overlap comparison subject and both specimens contained provisionally matching GBS). Genome sequencing confirmed common origin of provisionally matching fecal and blood isolates. The invasive E. coli were present in all presepticemic stools since birth, but gut colonization with GBS and S. marcescens occurred closer to time of bloodstream infection.

Conclusions: The neonatal gut harbors sepsis-causing pathogens, but such organisms are not inevitable members of the normal microbiota. Surveillance microbiology, decolonization, and augmented hygiene might prevent dissemination of invasive bacteria between and within premature infants.

Keywords: Escherichia coli; Serratia marcescens; group B streptococci; septicemia; whole-genome sequencing.

Figure 1.

Study flow chart. Abbreviations: GBS, group B Streptococcus; MRSA, methicillin-resistant Staphylococcus aureus.

Figure 2.

Precolonized case and overlap comparison group stool culture results. Case 1 annotations apply to all cases. Boxes in bottom rows represent 10 days before sepsis (including day of sepsis if stool was produced before blood culture was obtained). Box with number is day of sepsis; number denotes day of life the episode of sepsis occurred. Boxes above bottom row represent all overlap comparison group specimens relative to day of sepsis in corresponding case, including those collected on the day after sepsis (cases 3 and 6). Inset describes key to positive, negative, and nontested specimens. Abbreviation: GBS, group B Streptococcus.