Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients

Matthew S. Kelly*, Doyle V. Ward, Christopher J. Severyn, Mehreen Arshad, Sarah M. Heston, Kirsten Jenkins, Paul L. Martin, Lauren McGill, Andre Stokhuyzen, Shakti K. Bhattarai, Vanni Bucci, Patrick C. Seed

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.

Original languageEnglish (US)
Pages (from-to)2274-2280
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number11
DOIs
StatePublished - Nov 2019

Fingerprint

Hematopoietic Stem Cell Transplantation
Pediatrics
Wounds and Injuries
Infection
Cloaca
Anti-Bacterial Agents
Lactams
Vancomycin
Microbial Drug Resistance
Genomics
Gastrointestinal Tract
Cohort Studies
Genome
Prospective Studies
Escherichia coli

Keywords

  • Bloodstream infection
  • Hematopoietic stem cell transplantation
  • Microbiome

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Kelly, Matthew S. ; Ward, Doyle V. ; Severyn, Christopher J. ; Arshad, Mehreen ; Heston, Sarah M. ; Jenkins, Kirsten ; Martin, Paul L. ; McGill, Lauren ; Stokhuyzen, Andre ; Bhattarai, Shakti K. ; Bucci, Vanni ; Seed, Patrick C. / Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 11. pp. 2274-2280.
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abstract = "The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78{\%} were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99{\%} genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.",
keywords = "Bloodstream infection, Hematopoietic stem cell transplantation, Microbiome",
author = "Kelly, {Matthew S.} and Ward, {Doyle V.} and Severyn, {Christopher J.} and Mehreen Arshad and Heston, {Sarah M.} and Kirsten Jenkins and Martin, {Paul L.} and Lauren McGill and Andre Stokhuyzen and Bhattarai, {Shakti K.} and Vanni Bucci and Seed, {Patrick C.}",
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Kelly, MS, Ward, DV, Severyn, CJ, Arshad, M, Heston, SM, Jenkins, K, Martin, PL, McGill, L, Stokhuyzen, A, Bhattarai, SK, Bucci, V & Seed, PC 2019, 'Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients', Biology of Blood and Marrow Transplantation, vol. 25, no. 11, pp. 2274-2280. https://doi.org/10.1016/j.bbmt.2019.07.019

Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients. / Kelly, Matthew S.; Ward, Doyle V.; Severyn, Christopher J.; Arshad, Mehreen; Heston, Sarah M.; Jenkins, Kirsten; Martin, Paul L.; McGill, Lauren; Stokhuyzen, Andre; Bhattarai, Shakti K.; Bucci, Vanni; Seed, Patrick C.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 11, 11.2019, p. 2274-2280.

Research output: Contribution to journalArticle

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T1 - Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients

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AU - Ward, Doyle V.

AU - Severyn, Christopher J.

AU - Arshad, Mehreen

AU - Heston, Sarah M.

AU - Jenkins, Kirsten

AU - Martin, Paul L.

AU - McGill, Lauren

AU - Stokhuyzen, Andre

AU - Bhattarai, Shakti K.

AU - Bucci, Vanni

AU - Seed, Patrick C.

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N2 - The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.

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