title: Late-Onset Bloodstream Infection and Perturbed Maturation of the Gastrointestinal Microbiota in Premature Infants.
abstract: BACKGROUND
  Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.
  
  
  METHODS
  Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.
  
  
  RESULTS
  From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.
  
  
  CONCLUSIONS
  The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes.
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Shaw
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Sim
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Randell
authors.affiliation: Department of Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cox
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Zoë E
authors.initials: ZE
authors.lastname: McClure
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Li
authors.affiliation: Department of Microbiology, Imperial College NHS Trust, United Kingdom.
authors.forename: Hugo
authors.initials: H
authors.lastname: Donaldson
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langford
authors.affiliation: Department of Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: William O C M
authors.initials: WO
authors.lastname: Cookson
authors.affiliation: Department of Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.affiliation: Department of Medicine, Section of Paediatrics, Imperial College London, London, United Kingdom.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Kroll
mesh_terms: D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D064307:Microbiota; D018805:Sepsis / Q000175:diagnosis* / Q000382:microbiology