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We conducted a single-center retrospective cohort study of pediatric and adult allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 patients 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 28 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 (HR: 1.26 95% CI: 1.03-1.54) and acute GVHD mortality (HR: 1.63 95% CI: 1.08-2.46). Anaerobic antibiotics resulted in decreased gut bacterial diversity, depletion of Bifidobacteriales (P=0.04) and Clostridiales (P=0.01), and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome (P=0.04). Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment (P=0.001). 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.xref:EuropePMC:PMC7609492ENAantibiotic, graft-VS-host diseases, Disease, antibiotique, antimicrobials, Compounds, Stem Cell Transplantation, antimicrobial agents, Antibacterial Agent, Anti Mycobacterial Agents, Homologous Wasting Disease, Agent, homologous wasting disease, Relative, Graft-Versus-Host Diseases, microbicides, Anti Mycobacterial Agent, Relative Risks, Diseases, Antibiotic, microbicide, Bacteriocidal, Bacteriocidal Agents, Bacteriocide, Anti Bacterial Agent, Bacteriocides, Anti-Mycobacterial Agent, Antimycobacterial, antibiotics, Relative Risk, graft-versus-host disease, antimicrobial, Antimycobacterial Agents, Anti Bacterial Agents, Graft-Versus-Host Disease, Risk, Graft Versus Host Disease, Transplantation, Antibacterial, Antibiotika, Runt, susceptibility to, Risks, homologous wasting, Anti Bacterial Compounds, Anti Bacterial Compound, Graft-Versus-Host, Hematopoietic Stem Cell, Graft-vs-Host Diseases, Anti-Mycobacterial, Homologous Wasting, Anti-Bacterial Compounds, Runt Disease, Bacteriocidal Agent, Antibacterial Agents, Anti-Bacterial Agent, Graft-vs-Host, disease, Anti-Bacterial, resistance to, Agents, Anti-Mycobacterial Agents, Compound, Antimycobacterial Agent, graft-versus-host diseases, Antibiotics, Anti-Bacterial Compound, runt, Hematopoietic., Antibiotikum, Graft-vs-Host DiseasefalseAnaerobic Antibiotics and the Risk of Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation2023-05-172019-11-13PRJNA588783