P1156 Fidaxomicin for Clostridiodes difficile infection in inflammatory bowel disease: a multicenter retrospective cohort study
Authors: Noviello D , Chaparro M , Viganò C , Blesl A , Barberio B , Yanai H , Macaluso F , Ferreiro-Iglesias R , Bezzio C , Zilli A , Molnár T , Gheorghe C , Conforti F S , Innocenti T , Saibeni S , Bossuyt P , de Oliveira R F , Carvalhas Gabrielli A M , Losco A , Vieujean S , Tettoni E , Pirola L , Calderone S , Kornowski Cohen M , Dragoni G , Rath T , Barreiro-de Acosta M , Savarino E V , Gisbert J P , Vecchi M , Atreya R , Caprioli F 
Published: January 2025

Background

Inflammatory bowel disease (IBD) patients with Clostridiodes difficile Infection (CDI) are at increased risk of disease exacerbations, therapy escalation, colectomy, and mortality. Data on fidaxomicin use in IBD patients with CDI are very limited. We aimed to assess the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large retrospective multicenter cohort study.

Methods

Adult ulcerative colitis (UC) or Crohn’s disease (CD) patients with a CDI episode (positive toxin enzyme immunoassay or polymerase chain reaction for toxigenic C. difficile) treated with fidaxomicin for at least 7 consecutive days were included. The primary outcome was CDI recurrence rate, defined as C. difficile toxin detection and treatment with any antibiotic targeting CDI or faecal microbial transplantation within 8 weeks. Secondary outcomes included sustained response rate (no CDI treatment for 12 weeks), IBD therapy escalation, colectomy, and all-cause mortality at 30, 90, and 180 days. Pre-specified and any other adverse events were collected.

Results

A total of 96 patients (57 CD and 39 UC) were included from 20 European IBD centers. Patient demographics, IBD, and CDI characteristics are summarized in Tables 1 and 2. Most patients (73%) were on advanced IBD therapy, and 34% on steroids. Half of the patients were hospitalized, and 15% had a severe CDI episode. Half of the patients had a prior episode of CDI (30% with one, 21% with two or more), predominantly treated with vancomycin. Most patients (86%) received a fidaxomicin standard dose regimen, while 9 received extended-pulsed dosing. CDI recurrence occurred in 10 (10%) patients, while 79 (82%) patients achieved a sustained response. Compared to CDI-experienced patients, CDI naïve patients tended to have a lower recurrence (4.3 vs 16%; p=0.06) and higher sustained response (91 vs 75%; p=0.04) rate. Induction treatment with an IBD advanced therapy was required in 22 (24%), 18 (20%), and 11 (13%) patients at 30, 90, and 180 days, respectively. No difference in terms of CDI recurrence and sustained response was identified between CD and UC patients. Patients achieving, compared to not-achieving, CDI sustained response, showed a numerically lower need for IBD therapy escalation, with 2 (12%) vs 20 (26%), at day 30. Five UC patients underwent colectomy. A 79-year-old UC patient died unrelated to IBD or CDI. Mild episodes of rash, nausea, conjunctivitis, asthenia, hypokalemia, and hypocalcemia were reported.

Conclusion

In this large cohort of IBD patients with CDI, fidaxomicin was effective and safe for CDI resolution, with greater effectiveness for CDI first episodes. CDI resolution might influence short-term IBD-related outcomes, although further studies are required.