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Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation
Open accessAbstract
In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P < .001) and a decrease in fecal abundance of commensal Clostridiales (P = .03) compared with late antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P < .001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment.
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“and exposure to certain antibiotic agents at specific times is associated with transplantation-related mortality and GVHD-related mortality.10,16”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [16]
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Metadata
- Authors
- Weber, D., Jenq, R. R., Peled, J. U., Taur, Y., Hiergeist, A., Koestler, J., Dettmer, K., Weber, M., Wolff, D., Hahn, J., Pamer, E. G., Herr, W., Gessner, A., Oefner, P. J., van den Brink, M. R. M., & Holler, E.
- Affiliations
- University Hospital Regensburg (DE)
- The University of Texas MD Anderson Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Institute of Medical Microbiology and Hygiene (DE)
- University of Regensburg (DE)
- Corresponding author
- Weber, Daniela
- ORCID
- Venue
- Biology of Blood and Marrow Transplantation
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 23
- Issue
- 5
- Pages
- 845-852
- ISSN
- 1083-8791 (ISSN-L)
- PMC
- PMC5546237
- OpenAlex
- W2589011865
- Cited by
- 245
- References
- 34
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 23 · 2023: 20 · 2022: 20 · 2021: 37 · 2020: 34 · 2019: 29 · 2018: 28 · 2017: 11
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Transplantation and Cellular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- German Research Foundation (DFG, KFO's 234, 262)
- the Regensburg Center for Interventional Immunology, the Marie Curie Initial Training Network Celleurope, the ReForM program of the Regensburg School of Medicine, the National Institutes of Health (R01-HL124112, R01-HL069929, R01-AI080455, R01-AI101406, P01-CA023766)
- Project 4 (P01-CA023766, P30-CA008748, R01-AI042135, R01-AI095706, K23-AI095398)
- U.S National Institute of Allergy and Infectious Diseases (HHSN272200900059C)
- Mr. William H. Goodwin and Mrs. Alice Goodwin
- The Lymphoma Foundation
- Alex's Lemonade Stand
- The Geoffrey Beene Cancer Research Center at Memorial Sloan Kettering Cancer Center
- The Susan and Peter Solomon Divisional Genomics Program
- the Lucille Castori Center for Microbes, Inflammation, and Cancer, and the Tow Foundation
- European Union's Seventh Programme for research, technological development and demonstration (602587)
- German José Carreras Foundation (DJCLS R 11/09)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- allogeneic stem cell transplantation, broad-spectrum antibiotics, gut microbiota, timing of antibiotic administration, non-relapse mortality, Clostridiales, Clostridium cluster XIVa, indoxyl sulfate, graft-versus-host disease, overall survival
- MeSH terms
- Gastrointestinal Microbiome, Adult, Anti-Bacterial Agents, Clostridium, Female, Graft vs Host Disease, Humans, Infections, Male, Retrospective Studies, Risk Factors, Transplantation, Homologous, Survival Analysis, Treatment Outcome, Stem Cell Transplantation, Young Adult, Time-to-Treatment
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