Background. Fecal microbiota transplantation (FMT) is recommended to prevent the recurrence of Clostridioides difficile infection (CDI) following failure of antibiotic treatments alone. However, some patients do not respond to this treatment and remain refractory to repeat FMT. The best treatment strategy for patients who fail FMT remains undetermined. We have demonstrated previously that FMT failure can result from delayed engraftment of key microbial bacterial taxa. Therefore, we hypothesized that extending the symptom-free period following repeat FMT using monoclonal antibody blockade of C. difficile toxin B would constitute a successful rescue protocol.

Methods. Twenty-seven consecutive patients who failed initial FMT in treatment of recurrent CDI at two medical centers (University of Minnesota and Brown University) were treated with the rescue protocol consisting of three elements:

1) retreatment with vancomycin or fidaxomicin;
2) administration of bezlotoxumab (BEZ) toward the end of the antibiotic treatment course;
3) single administration of MTP-101C, a standardized, encapsulated preparation of freeze-dried healthy donor microbiota containing ~ 5 x 10¹¹ bacteria in 3-5 capsules.

Cure was defined as an absence of diarrhea associated with positive laboratory testing for C. difficile for at least 8 weeks following repeat FMT.

Results. Our cohort of patients who failed initial FMT treatment was characterized by advanced age, moderate to severe Charlson Comorbidity Index (i.e., ≥ 3), and polypharmacy (Table). The rescue protocol was successful in 24/27 patients (89%), which is superior to our prior 56% success rate after repeat FMT using oral capsules or colonoscopic administration alone (p = 0.012).

Discussion and Conclusions. Co-administration of BEZ appears to enhance efficacy of repeat encapsulated FMT in patients who fail an initial FMT. The pharmacokinetics of MTP-101C suggests that the blockade of toxin B provides protection from symptoms during the time necessary for the engraftment of key bacterial taxa. Our initial data supports this hypothesis, although further studies should be done. The added benefit of BEZ may also be considered with repeat treatments using currently available commercial fecal microbiota-based drugs, live-jslm (Rebyota) and live-brpk (Vowst).

Nataliia Kuchma

Appearances