Fidaxomicin for Clostridioides difficile infection in patients with inflammatory bowel disease: a multicentre retrospective cohort study

Background and aims: Inflammatory bowel disease (IBD) patients with Clostridioides difficile infection (CDI) are at increased risk of adverse outcomes. Data on fidaxomicin use in IBD remains scarce. We assessed the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large international cohort. Methods: Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) treated with fidaxomicin for documented CDI were retrospectively included. The primary outcome was CDI recurrence rate within 8 weeks (C. difficile toxin detection and CDI-targeted therapy). Secondary outcomes included sustained response (no CDI-targeted therapy within 12 weeks), IBD therapy escalation, colectomy rate, and all-cause mortality within 30, 90, and 180 days. Results: Ninety-six patients (57 UC and 39 CD) from 20 IBD centres were included. Most were on advanced IBD therapy. Half had a previous CDI episode, 15% a severe episode. CDI recurrence rate was 10% at week 8, sustained response 82% at week 12. Compared to patients with previous CDI episode, patients at first episode tended to have a lower recurrence (4.3 vs 16%; p=0.06) and higher sustained response (91 vs 75%; p=0.04) rate. IBD therapy escalation was required in 48% with a numerically lower need for patients achieving vs not-achieving sustained response within 30 days (12 vs 20%; p=0.42). Five UC patients underwent colectomy. One death unrelated to CDI or IBD occurred. One moderate and five mild adverse events were reported. Conclusions: Fidaxomicin was effective and safe in IBD patients with CDI, with greater effectiveness in CDI-naïve patients, potentially influencing short-term IBD outcomes.