Restrictive versus permissive use of broad-spectrum antibiotics in patients receiving allogeneic SCT and early fever due to cytokine release syndrome: Evidence for beneficial microbiota protection without increase of infectious complications.

BACKGROUND: Intestinal microbiota contribute to the pathophysiology of acute gastrointestinal (GI) Graft-versus-Host Disease (aGvHD) and loss of microbiome diversity influences the outcome of patients after allogeneic stem cell transplantation (SCT). Systemic broad-spectrum antibiotics have been identified as a major cause of early microbiota dysbiosis.

METHODS: In 2017 our transplant unit at the university hospital in Regensburg changed the antibiotic strategy from a permissive way with initiation of antibiotics in all patients with neutropenic fever independent of the underlying cause and risk to a restrictive use in cases with high likelihood of cytokine release syndrome e.g., after Antithymocyte globulin (ATG) therapy. We analyzed clinical data and microbiome parameters obtained 7 days after allogeneic SCT from 188 patients with ATG therapy transplanted in 2015/2016 (permissive cohort, n=101) and 2918/2019 (restrictive cohort, n=87).

RESULTS: Restrictive antibiotic treatment postponed the beginning of antibiotic administration from 1.4 ± 7.6 days prior to 1.7 ± 5.5 days after SCT (p=0.01) and significantly reduced the duration of antibiotic administration by 5.8 days (p<0.001) without increase of infectious complications. Furthermore, we observed beneficial effects of the restrictive strategy compared to the permissive way on microbiome diversity (urinary 3-indoxylsulfate, p=0.01; Shannon and Simpson indices, p<0.001) and species abundance 7 days posttransplant as well as a positive trend toward a reduced incidence of severe GI GvHD (p=0.1).

CONCLUSIONS: Our data indicate that microbiota protection can be achieved by a more careful selection of neutropenic patients qualifying for antibiotic treatment during allogeneic SCT without increased risk for infectious complications.