RT Journal Article SR Electronic T1 Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP 242 DO 10.1186/s40425-019-0714-x VO 7 IS 1 A1 Hamzah Abu-Sbeih A1 Lauren Nicholas Herrera A1 Tenglong Tang A1 Mehmet Altan A1 Anne-Maria P. Chaftari A1 Pablo C. Okhuysen A1 Robert R. Jenq A1 Yinghong Wang YR 2019 UL http://jitc.bmj.com/content/7/1/242.abstract AB Background The gut microbiome impacts the efficacy of immune checkpoint inhibitor (ICI) therapy and the development of ICI-mediated diarrhea and/or colitis (IMDC). Antibiotic therapy,especially that with anaerobic activity, has profound effects on the gut microbiome. Therefore, we sought to assess the effect of antibiotics on the development of IMDC.Methods Patients who received ICI therapy from January 2016 to January 2018 were examined retrospectively. A Cox regression model was used to assess factors associated with overall survival.Results A total of 826 patients were included. Of these patients, 51.6% received inhibitors of programmed cell death protein-1 or its ligand, 32.0% received inhibitors of cytotoxic T-lymphocyte-associated antigen-4, and 16.5% received a combination of the two. IMDC occurred in 52.5% of the patients after a median of 8 weeks. Overall, 569 patients (68.9%) received antibiotic therapy. Antibiotic use at any time was associated with reduced IMDC occurrence and recurrence rates but also with frequent hospitalization and intensive care unit admission for IMDC as well as increased IMDC severity. Compared with patients who received antibiotic therapy only before ICI therapy initiation, those receiving it after ICI had a higher IMDC rate and more often needed immunosuppressive therapy and hospitalization for IMDC. Antibiotics with anaerobic activity were included in 51% of the antibiotic therapy regimens and were associated with increased immunosuppressant use, hospitalization, intensive care unit admission for IMDC, and severe IMDC grades. Forty-one patients received empiric prophylactic antibiotic therapy at IMDC onset. These patients more often needed immunosuppressive therapy, intravenous steroids, and infliximab/vedolizumab; had more frequent and longer hospitalization for IMDC and higher IMDC grades; and more frequently had IMDC recurrence than did patients who did not receive antibiotic therapy at the time of IMDC symptom onset.Conclusions Whereas antibiotic therapy appeared to be protective against IMDC onset, use of antibiotics, especially those with anaerobic activity, after ICI therapy was associated with increased risk of severe IMDC.A correction to this article is available online at https://doi.org/10.1186/s40425-019-0832-5.Abbreviations:CTLA-4Cytotoxic T-lymphocyte-associated antigen 4FMTFecal microbiota transplantationICIImmune checkpoint inhibitorICUIntensive care unitIMDCImmune-mediated diarrhea and colitisIQRInterquartile rangeirAEImmunotherapy-related adverse eventPD-1Programmed cell death protein 1PD-L1Programmed death-ligand 1SDStandard deviation