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Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Publication ,  Journal Article
Tanaka, JS; Young, RR; Heston, SM; Jenkins, K; Spees, LP; Sung, AD; Corbet, K; Thompson, JC; Bohannon, L; Martin, PL; Stokhuyzen, A; Ward, DV ...
Published in: Biol Blood Marrow Transplant
November 2020

Certain anaerobic bacteria are important for maintenance of gut barrier integrity and immune tolerance and may influence the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center retrospective cohort study of allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 children and adults who developed febrile neutropenia between 7 days before and 28 days after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n = 491) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, cefepime, or ceftazidime; n = 723). We performed metagenomic sequencing of serial fecal samples from 36 pediatric patients to compare the effects of specific antibiotics on the gut metagenome. Receipt of anaerobic antibiotics was associated with higher hazards of acute gut/liver GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.03 to 1.54) and acute GVHD mortality (HR, 1.63; 95% CI, 1.08 to 2.46), but not chronic GVHD diagnosis (HR, 1.04; 95% CI: .84 to 1.28) or chronic GVHD mortality (HR, .88; 95% CI, .53 to 1.45). Anaerobic antibiotics resulted in decreased gut bacterial diversity, reduced abundances of Bifidobacteriales and Clostridiales, and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome. Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment. Our findings demonstrate that exposure to anaerobic antibiotics is associated with increased risks of acute gut/liver GVHD and acute GVHD mortality after allogeneic HSCT. Use of piperacillin-tazobactam or carbapenems should be reserved for febrile neutropenia cases in which anaerobic or multidrug-resistant infections are suspected.

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Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

November 2020

Volume

26

Issue

11

Start / End Page

2053 / 2060

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Retrospective Studies
  • Immunology
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Graft vs Host Disease
  • Child
  • Anti-Bacterial Agents
  • Anaerobiosis
  • Adult
 

Citation

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Tanaka, J. S., Young, R. R., Heston, S. M., Jenkins, K., Spees, L. P., Sung, A. D., … Kelly, M. S. (2020). Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant, 26(11), 2053–2060. https://doi.org/10.1016/j.bbmt.2020.07.011
Tanaka, John S., Rebecca R. Young, Sarah M. Heston, Kirsten Jenkins, Lisa P. Spees, Anthony D. Sung, Kelly Corbet, et al. “Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant 26, no. 11 (November 2020): 2053–60. https://doi.org/10.1016/j.bbmt.2020.07.011.
Tanaka JS, Young RR, Heston SM, Jenkins K, Spees LP, Sung AD, et al. Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2020 Nov;26(11):2053–60.
Tanaka, John S., et al. “Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant, vol. 26, no. 11, Nov. 2020, pp. 2053–60. Pubmed, doi:10.1016/j.bbmt.2020.07.011.
Tanaka JS, Young RR, Heston SM, Jenkins K, Spees LP, Sung AD, Corbet K, Thompson JC, Bohannon L, Martin PL, Stokhuyzen A, Vinesett R, Ward DV, Bhattarai SK, Bucci V, Arshad M, Seed PC, Kelly MS. Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2020 Nov;26(11):2053–2060.
Journal cover image

Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

November 2020

Volume

26

Issue

11

Start / End Page

2053 / 2060

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Retrospective Studies
  • Immunology
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Graft vs Host Disease
  • Child
  • Anti-Bacterial Agents
  • Anaerobiosis
  • Adult