ArticleTransplantation and cellular therapy2021
Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease
Article in Transplantation and cellular therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation.JCI insight · 2022Trial
- The intestinal microbiota as a key modulator of acute graft-versus-host disease.Nature reviews. Cancer · 2026Review
- Antibiotic risk score for acute graft-versus-host disease.Blood advances · 2026Article
- Microbiome Modulation in Pediatric Leukemia: Impact on Graft-Versus-Host Disease and Treatment Outcomes: A Narrative Review.Children (Basel, Switzerland) · 2025Review
- Review
- Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation.JAMA network open · 2023Article
- Evaluating the Use of Meropenem in Hematologic Patients with Febrile Neutropenia: A Retrospective Observational Single-Cohort Study.Mediterranean journal of hematology and infectious diseases · 2023Article
- Article
- Piperacillin/Tazobactam and Meropenem Use Increases the Risks for Acute Graft Rejection Following First Kidney Transplantation.Journal of clinical medicine · 2022Article
- Article
- Roles of the intestinal microbiota and microbial metabolites in acute GVHD.Experimental hematology & oncology · 2021Review
- Review
- Altered intestinal microbiome and epithelial damage aggravate intestinal graft-versus-host disease.Gut microbesReview
Corrections and comments
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Authors and funding
26 authors at 18 institutions in 3 countries.
Funding
Abstract
Variation in the gastrointestinal (GI) microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD risk in pediatric patients undergoing HCT for acute leukemia. We performed a retrospective analysis in a dataset merged from 2 sources: (1) the Center for International Blood and Marrow Transplant Research, an observational transplantation registry, and (2) the Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to 3 classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) antipseudomonal penicillins, and (3) carbapenems. The primary outcome was grade II-IV aGVHD; secondary outcomes were grade III-IV aGVHD and lower GI GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (subcohort) included transplantation characteristics, GVHD risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2550 patients at 36 centers; the subcohort included 1174 patients. In adjusted models, carbapenems were associated with an increased risk of grade II-IV aGVHD in the full cohort (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.02 to 1.51) and subcohort (sub hazard ratio [HR], 1.31; 95% CI, 0.99 to 1.72), as well as with an increased risk of grade III-IV aGVHD (subHR, 1.77; 95% CI, 1.25 to 2.52). Early carbapenem exposure (before day 0) especially impacted aGVHD risk. For antipseudomonal penicillins, the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad-spectrum antibiotics, should be used judiciously in pediatric HCT recipients to minimize aGVHD risk. Further research is needed to clarify the mechanism underlying this association.
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