TY - JOUR
T1 - Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients
AU - Kelly, Matthew S.
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.
N1 - Funding Information:
The authors thank F. Tamburini and A. Bhatt for their feedback on the study design and data analyses, as well as all the children and families who participated in this study. Financial disclosure: This work was supported by research grants from the Derfner Foundation and the Children's Miracle Network. Additional support was provided by the National Institute of Allergy and Infectious Diseases (Grant UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. M.S.K. was supported by a National Institutes of Health Career Development Award (Grant K23-AI135090). V.B. was supported by the National Institute of Allergy and Infectious Diseases (Grant R15-AI112985-01A1) and the National Science Foundation (Grant 1458347). Authorship statement: M.S.K. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; he designed and led the project, collected data, drafted the manuscript, and approved the final manuscript as submitted. D.V.W. S.K.B. V.B. provided statistical analysis, critically reviewed the manuscript, and approved the final manuscript as submitted. S.M.H. P.L.M. and L.M. critically reviewed the manuscript and approved the final manuscript as submitted. K.J. A.S. P.L.M. C.J.S. M.A. and P.C.S. contributed to project design and implementation, critically reviewed the manuscript, and approved the final manuscript as submitted.
Funding Information:
Financial disclosure: This work was supported by research grants from the Derfner Foundation and the Children's Miracle Network. Additional support was provided by the National Institute of Allergy and Infectious Diseases (Grant UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. M.S.K. was supported by a National Institutes of Health Career Development Award (Grant K23-AI135090). V.B. was supported by the National Institute of Allergy and Infectious Diseases (Grant R15-AI112985-01A1) and the National Science Foundation (Grant 1458347).
Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy
PY - 2019/11
Y1 - 2019/11
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.
AB - 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.
KW - Bloodstream infection
KW - Hematopoietic stem cell transplantation
KW - Microbiome
UR - http://www.scopus.com/inward/record.url?scp=85070203585&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.07.019
DO - 10.1016/j.bbmt.2019.07.019
M3 - Article
C2 - 31326608
AN - SCOPUS:85070203585
SN - 1083-8791
VL - 25
SP - 2274
EP - 2280
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -