Abstract
BACKGROUND: Broad-spectrum antibiotics are standard for febrile neutropenia (FN) in allogeneic hematopoietic stem cell transplantation (HSCT) but may disrupt gut microbiota, increasing the risk of graft-versus-host disease (GVHD). However, current evidence on the effects of anaerobic versus limited anaerobic antibiotic coverage on GVHD-related outcomes remains inconclusive. METHODS: We systematically searched for studies assessing overall survival, acute GVHD incidence, and GVHD-related mortality in patients with allogeneic HSCT receiving antibiotics with anaerobic versus limited anaerobic coverage. A random-effects meta-analysis calculated risk ratios (RRs) and 95% confidence intervals (CIs) after assessing bias risk. RESULTS: Six of the 323 screened studies met the inclusion criteria, encompassing 2169 patients: five studies included adult populations, and one included a pediatric population. Meta-analysis revealed no significant difference in 1-year overall survival between the anaerobic and the limited anaerobic coverage groups (RR: 1.01; 95% CI: 0.92-1.12). Acute GVHD incidence was significantly higher in the anaerobic coverage group than in the limited anaerobic coverage group (RR: 1.33; 95% CI: 1.17-1.51). GVHD-related mortality tended to be higher in the anaerobic coverage group than in the limited coverage group (RR: 1.65; 95% CI: 0.94-2.91). Of the six studies, three had a high risk of bias. Moderate heterogeneity was observed between citations regarding GVHD-related mortality (I(2) = 63%). CONCLUSION: Antibiotics with anaerobic coverage appear to increase acute GVHD incidence in patients who received an allogeneic HSCT compared to antibiotics with limited anaerobic coverage. However, the strength of this conclusion is limited by the quality of available evidence. Further well-designed research is necessary to clarify the impact of anaerobic antibiotic coverage on GVHD-related outcomes.