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For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow\u2010spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non\u2010antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non\u2010toxigenic <jats:italic>C. difficile<\/jats:italic> and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies. <jats:italic>Curr. Protoc. 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