Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection — An observational cohort study

•For 271 patients with Clostridioides difficile (CDI) clinical outcome was recorded (sustained clinical cure or recurrence).•Fidaxomicin was a superior treatment to metronidazole or vancomycin in the initial episode.•Fidaxomicin was a superior treatment to metronidazole or vancomycin in the first recurrence.•Fidaxomicin was a superior treatment to metronidazole or vancomycin in non-severe CDI.•Fidaxomicin had a similar treatment outcome to vancomycin in severe and multiple recurrent CDI. We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. An observation cohort study included 271 CDI patients hospitalised between 2013–2016. Univariate logistic regression was used to evaluate the association between patients’ clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.