Low Diversity in Nasal Microbiome Associated With Colonization and Bloodstream Infections in Hospitalized Neonates.

Ni Zhao, Dina F Khamash, Hyunwook Koh, Annie Voskertchian, Emily Egbert, Emmanuel F Mongodin, James R White, Lauren Hittle, Elizabeth Colantuoni, Aaron M Milstone
Author Information
  1. Ni Zhao: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. ORCID
  2. Dina F Khamash: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  3. Hyunwook Koh: Deptartment of Applied Mathematics & Statistics, The State University of New York, Korea (SUNY Korea), Incheon, South Korea.
  4. Annie Voskertchian: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  5. Emily Egbert: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  6. Emmanuel F Mongodin: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  7. James R White: Resphera Biosciences, Baltimore, Maryland, USA.
  8. Lauren Hittle: Resphera Biosciences, Baltimore, Maryland, USA.
  9. Elizabeth Colantuoni: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
  10. Aaron M Milstone: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

BACKGROUND: is a leading cause of infectious morbidity and mortality in neonates. Few data exist on the association of the nasal microbiome and susceptibility to neonatal colonization and infection.
METHODS: We performed 2 matched case-control studies (colonization cohort-neonates who did and did not acquire colonization; bacteremia cohort-neonates who did [colonized neonates] and did not [controls] acquire colonization and neonates with bacteremia [bacteremic neonantes]). Neonates in 2 intensive care units were enrolled and matched on week of life at time of colonization or infection. Nasal samples were collected weekly until discharge and cultured for and the nasal microbiome was characterized using 16S rRNA gene sequencing.
RESULTS: In the colonization cohort, 43 -colonized neonates were matched to 82 controls. At 1 week of life, neonates who acquired colonization had lower alpha diversity (Wilcoxon rank-sum test < .05) and differed in beta diversity (omnibus MiRKAT = .002) even after adjusting for birth weight ( = .01). The bacteremia cohort included 10 neonates, of whom 80% developed bacteremia within 4 weeks of birth and 70% had positive cultures within a few days of bacteremia. Neonates with bacteremia had an increased relative abundance of sequences and lower alpha diversity measures compared with colonized neonates and controls.
CONCLUSIONS: The association of increased abundance and decrease of microbiome diversity suggest the need for interventions targeting the nasal microbiome to prevent disease in vulnerable neonates.

Keywords

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Grants

  1. K24 AI141580/NIAID NIH HHS
  2. R01 HS022872/AHRQ HHS
  3. R21 AI135179/NIAID NIH HHS
  4. U54 CK000617/NCEZID CDC HHS

Word Cloud

Created with Highcharts 10.0.0neonatescolonizationbacteremiamicrobiomediversitynasalinfectionmatchedNeonatesassociation2cohort-neonatesacquireweeklifeNasalcohortcontrolsloweralpha=birthwithinincreasedabundanceBACKGROUND:leadingcauseinfectiousmorbiditymortalitydataexistsusceptibilityneonatalMETHODS:performedcase-controlstudies[colonizedneonates][controls][bacteremicneonantes]intensivecareunitsenrolledtimesamplescollectedweeklydischargeculturedcharacterizedusing16SrRNAgenesequencingRESULTS:43-colonized821acquiredWilcoxonrank-sumtest<05differedbetaomnibusMiRKAT002evenadjustingweight01included1080%developed4weeks70%positiveculturesdaysrelativesequencesmeasurescomparedcolonizedCONCLUSIONS:decreasesuggestneedinterventionstargetingpreventdiseasevulnerableLowDiversityMicrobiomeAssociatedColonizationBloodstreamInfectionsHospitalizedStaphylococcusaureusbloodstream

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