Study Describes Therapeutic Strategies for Improving FMT Success for C Diff

New research is shedding light on potential strategies for improving the effectiveness of fecal microbiota transplantation (FMT) for the treatment of Clostridioides difficile infection (CDI).¹

The study enrolled > 1000 adult patients with CDI treated with FMT at the Centre for Faecal Microbiota Transplantation (CEFTA) at Aarhus University Hospital and found the most effective FMT treatment strategy involved administering FMT as multiple-dose capsules or colonoscopy after an extended period of antibiotic pretreatment, regardless of CDI episode, and providing repeated FMT in patients with CDI recurrence. Of note, antibiotic pretreatment choice and prophylactic vancomycin in patients needing antibiotics following FMT did not impact outcomes.¹

Current treatment guidelines from the American Gastroenterological Association recommend the use of FMT-based therapy in patients with recurrent CDI at high risk of recurrence following standard-of-care antibiotics and in hospitalized patients with severe CDI after standard-of-care antibiotics if there is no improvement.²

“Real-world data indicate that one-third of patients do not respond adequately to their first FMT treatment, highlighting the need to optimize FMT treatment strategies,” Sara Ellegaard Paaske, a PhD student in the department of clinical medicine at Aahrus University, and colleagues wrote, calling attention to the current lack of large-scale systematic evidence to guide the decision on when to switch from repeated FMT treatments to antibiotic treatments or to assess the effectiveness of antibiotics in patients recently treated with FMT.¹

To address this gap in research and inform a rational clinical approach to FMT treatment for CDI, investigators conducted a multisite cohort study in the Central and North Denmark Regions. Eligible patients were ≥ 18 years of age with CDI treated with FMT applied through capsules, nasojejunal tube, or colonoscopy. CDI was defined as C. difficile-associated diarrhea (CDAD), characterised as diarrhea (≥ 3 daily Bristol Stool Form Scale 6–7) coupled with a positive C. difficile test.¹

The primary outcome was cure of CDAD 8 weeks after treatment, with cure failure defined as CDAD recurrence, suspected CDAD recurrence, death, or colectomy. Patients were followed until achieving CDAD cure 8 weeks after treatment or until they underwent colectomy, were lost to follow-up, or died.¹

Variables related to the FMT treatment strategy were categorised into pretreatment, FMT, and follow-up and included variation in choice and length of antibiotic pretreatment, FMT administration, FMT dosing, and use of prophylactic vancomycin in patients needing non-CDI antibiotics during follow-up.¹

From May 2016 to December 2023, investigators treated 1200 patients with CDI with FMT applied through capsules, nasojejunal tube, or colonoscopy at 10 hospital departments. Of these patients, 30 were lost to follow-up, leaving 1170 patients who received 1643 FMT treatments for inclusion.¹

Investigators noted vancomycin was the most common antibiotic pretreatment (91%), and capsule FMT was the most frequently used FMT administration (80%).¹

Among the included patients, 699 (60%; 95% CI, 57–63%) achieved cure at week 8 following their first FMT treatment, 342 (29%; 95% CI, 27–32%) had verified recurrence within 8 weeks, 49 (4%; 95% CI, 3–6%) had suspected recurrence in the 8-week follow-up, 73 (6%; 95% CI, 5–8%) died during follow-up, and 7 (1%; 95% CI, 0–1%) received colectomy in the follow-up.¹

Of the 393 patients with verified or suspected recurrence of CDAD, 326 (83%) were treated with up to 5 FMT treatments. Following repeated FMT treatments, 944 patients (81%; 95% CI, 78–83%) achieved CDAD cure at the 8-week follow-up, and 113 had CDAD recurrence or suspected CDAD recurrence (10%; 95% CI, 8–11%).¹

Upon analysis, prolonged antibiotic pretreatment was associated with greater cure rates (65%; odds ratio [OR], 1.22; 95% CI, 1.10–1.36; P <.001). Additionally, investigators noted FMT administration through oral, multi-dose capsules (69%; OR, 1.19; 95% CI, 1.11–1.27; P <.001) or colonoscopy (69%; OR, 1.14; 95% CI, 1.04–1.24; P = .01) resulted in the greatest cure rates.¹

Of note, neither antibiotic pretreatment type nor prophylactic vancomycin during non-CDI antibiotics affected cure rates, and in patients for whom FMT was initially unsuccessful, repeated FMT was more effective than antibiotic treatment alone.¹

“In conclusion, the most effective FMT treatment strategy involved administering FMT as multiple-dose capsules or colonoscopy after an extended period of antibiotic pretreatment, regardless of CDI episode, and providing repeated FMT in patients with CDI recurrence,” investigators wrote.¹ “Future guidelines should address FMT dosing, administration methods, and pretreatment duration to assist clinicians in selecting strategies with the highest likelihood of success.”

References

1. Paaske SE, Baunwall SMD, Rubak T, et al. Clinical management of Clostridioides difficile infection with faecal microbiota transplantation: a real-world cohort study. EClinicalMedicine. doi:10.1016/j.eclinm.2025.103302

2. Brooks A. AGA Supports Fecal Microbiota-Based Therapies for C Diff in New Guideline. HCPLive. February 21, 2024. Accessed July 16, 2025. https://www.hcplive.com/view/aga-supports-fecal-microbiota-based-therapies-for-c-diff-in-new-guideline