title: Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany. Electronic address: daniela.weber@ukr.de.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weber
authors.affiliation: Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Jonathan U
authors.initials: JU
authors.lastname: Peled
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York; Infectious Diseases Services, Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ying
authors.initials: Y
authors.lastname: Taur
authors.affiliation: Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hiergeist
authors.affiliation: Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Koestler
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Dettmer
authors.affiliation: Department of Orthopedic Surgery, University Medical Center, Regensburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.affiliation: Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York; Infectious Diseases Services, Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.affiliation: Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Gessner
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oefner
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Marcel R M
authors.initials: MRM
authors.lastname: van den Brink
authors.affiliation: Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D003013:Clostridium / Q000187:drug effects; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D061665:Time-to-Treatment; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents
keywords: Acute intestinal GVHD; Allogeneic stem cell transplantation; Intestinal microbiome; Outcome; Treatment with broad-spectrum antibiotics