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Without doubt, there is an urgent need for new effective anticlostridial agents due to the increasing incidence and severity of <jats:italic>C. difficile<\/jats:italic> infection (CDI). The aim of the present study is to investigate the <jats:italic>in vivo<\/jats:italic> efficacy of auranofin (rheumatoid arthritis FDA-approved drug) in a CDI mouse model and establish an adequate dosage for treatment. The effects of increased <jats:italic>C. difficile<\/jats:italic> inoculum, and pre-exposure to simulated gastric intestinal fluid (SGF) and simulated intestinal fluid (SIF), on the antibacterial activity of auranofin were investigated. Auranofin\u2019s <jats:italic>in vitro<\/jats:italic> antibacterial activity was stable in the presence of high bacterial inoculum size compared to vancomycin and fidaxomicin. Moreover, it maintained its anti-<jats:italic>C. difficile<\/jats:italic> activity after being exposed to SGF and SIF. Upon testing in a CDI mouse model, auranofin at low clinically achievable doses (0.125\u2009mg\/kg and 0.25\u2009mg\/kg) significantly protected mice against CDI with 100% and 80% survival, respectively. Most importantly, auranofin (0.125\u2009mg\/kg and 0.25\u2009mg\/kg) significantly prevented CDI recurrence when compared with vancomycin. Collectively, these results indicate that auranofin could potentially provide an effective, safe and quick supplement to the current approaches for treating CDI.<\/jats:p>","DOI":"10.1038\/s41598-020-64882-9","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T10:03:18Z","timestamp":1588845798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Auranofin, at clinically achievable dose, protects mice and prevents recurrence from Clostridioides difficile infection"],"prefix":"10.1038","volume":"10","author":[{"given":"Nader S.","family":"Abutaleb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"64882_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1786-6","volume":"16","author":"S Zhang","year":"2016","unstructured":"Zhang, S. et al. 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