Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection

Austin Hoeg; Nataliia Kuchma; Andrew Krane; Carolyn Graiziger; Juana Thomas; Colleen R Kelly; Alexander Khoruts

doi:10.1097/MCG.0000000000002108

Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection

J Clin Gastroenterol. 2024 Nov 21. doi: 10.1097/MCG.0000000000002108. Online ahead of print.

Authors

Austin Hoeg¹, Nataliia Kuchma¹, Andrew Krane², Carolyn Graiziger¹, Juana Thomas², Colleen R Kelly³, Alexander Khoruts¹

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN.
² Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI.
³ Division of Gastroenterology, Department of Medicine, Harvard Medical School, Boston, MA.

PMID: 39621384
DOI: 10.1097/MCG.0000000000002108

Abstract

Goals: Evaluate the benefit of adding bezlotoxumab to repeat fecal microbiota transplantation (FMT) in patients with recurrent Clostridioides difficile infections after the failure of FMT alone.

Background: The initial failure of FMT in breaking the cycle of recurrent Clostridium difficile(C. difficile) infections is associated with a greater risk of subsequent failure. Our previous analysis showed that FMT failure is associated with delayed repair of fecal microbiota at 1 week after administration. We hypothesized that increasing the symptom-free interval by adding bezlotoxumab would improve the outcomes of a second FMT.

Study: A new rescue protocol that combines FMT with bezlotoxumab for patients who previously failed FMT alone was implemented in 2 academic medical centers. The clinical outcomes of a new protocol were captured in a prospective registry. The results were compared in a retrospective analysis of clinical outcomes of prior experience with repeat FMT by itself. All FMT preparations were standardized for dose. Bezlotoxumab administration was synchronized temporally with the second FMT to maximize its duration of action.

Results: Our historical cure rate of second FMT in treatment of recurrent C. difficile infection was 48% (15/31 patients). Addition of bezlotoxumab to the second FMT resulted in a cure rate of 89% (24/27 patients).

Conclusions: Addition of bezlotoxumab markedly improved the cure rate of the second FMT following initial FMT failure. The rationale for the protocol design highlights the importance of understanding the pharmacokinetics of both bezlotoxumab and FMT. Similar principles may apply to other live biotherapeutic products that are becoming available for prevention of C. difficile infection recurrence.