A Third Clostridioides difficile Recurrence: Choosing Among Three Ways to Rebuild a Microbiome
A single patient with a third recurrence of Clostridioides difficile infection, comparing a live biotherapeutic product against traditional fecal transplant after the monoclonal antibody adjunct was withdrawn from the market.
Frank D., a 72-year-old man and retired mail carrier, has been through this cycle twice already this year: diarrhea resolves on a vancomycin taper, life returns to normal for a few weeks, and then it starts again — watery stools six to eight times a day, cramping, and the same PCR-confirmed C. difficile each time. This is his third recurrence, each one following completed, guideline-appropriate antibiotic therapy, and his wife has started keeping a log of his bathroom trips on the kitchen calendar because neither of them can otherwise keep track of which cycle they're in anymore. He has no other major medical problems beyond well-controlled hypertension, is not immunocompromised, and has had no additional antibiotic exposures beyond what's been prescribed for the C. difficile itself.
A third recurrence is exactly the point at which guidelines and real practice both move past repeating the same antibiotic taper and toward something aimed at the actual mechanism keeping the cycle going — a microbiome too disrupted by repeated antibiotic courses to resist C. difficile recolonization on its own. Two real options remain, and a third has just been taken off the table. Fecal microbiota, live-jslm (marketed as Rebyota) and fecal microbiota spores, live-brpk (marketed as Vowst) are both FDA-approved live biotherapeutic products, studied specifically in patients with recurrent disease after standard antimicrobial therapy and each showing meaningfully reduced recurrence compared to placebo in their pivotal trials. A third option existed until recently and is worth naming precisely because it no longer does: bezlotoxumab, a monoclonal antibody against C. difficile toxin B, given as a single infusion alongside a current antibiotic course rather than after it, and shown in the MODIFY I and MODIFY II trials to reduce recurrence at that earlier point. Merck discontinued it as of January 31, 2025 as the sole supplier, with no biosimilar, so the one agent that acted during Frank's vancomycin taper rather than after it is simply not available to order — which removes the option of covering both windows and forces the whole decision into the post-antibiotic one. Traditional fecal microbiota transplant, typically colonoscopic, remains the option with the longest track record and the highest reported real-world success rates in exactly this recurrent population, even without the same randomized regulatory pathway the two newer products completed. Frank doesn't need convincing that something has to change. What the group has lost is the ability to hedge across two mechanisms at once, which makes the single post-antibiotic choice carry more weight for him than it would have a year ago.
Clinic, deciding after a third recurrence
I'd move to fecal microbiota spores, live-brpk after this taper completes. It's FDA-approved specifically for recurrent C. difficile after standard antimicrobial therapy, oral rather than requiring a procedure, and its pivotal trial showed a meaningful, statistically significant reduction in recurrence against placebo in a population that looks like Frank's own history.
My instinct is to cover the window during the taper, not just after it — MODIFY I and MODIFY II both found bezlotoxumab reduced recurrence given alongside standard-of-care antibiotic therapy, and that is genuinely a different and earlier point in the process than any microbiome product given afterward. Except I went to order it last month for someone else and couldn't: Merck discontinued it in January 2025 and there's no biosimilar. So I'll say plainly that the option I'd want doesn't exist anymore, and that it changes what I think about the one that's left.
That withdrawal matters more than it might look, and I'd take the inference in the opposite direction from where instinct pulls. If we could still cover the taper window, I'd be relaxed about which post-antibiotic option we picked, because a miss on one would be partly insured by the other. We can't, so whatever we choose after the taper is carrying the whole recurrence-prevention burden by itself — and that argues for the option with the highest reported cure rate rather than the most standardized one. Traditional colonoscopic FMT still holds that position for recurrent disease specifically, even without the randomized approval pathway the newer products completed. For a first recurrence I'd say the reverse; for a third, with no adjunct available, I want the highest number.
Agreed: the vancomycin taper completed as planned, followed by colonoscopic FMT once stool clears of active symptoms — a single-mechanism plan rather than the two-mechanism one the group would have written eighteen months ago. Not fully agreed: whether losing the toxin-directed adjunct should have pushed the choice toward FMT or away from it. The pharmacologist read it as an argument for the highest reported cure rate, since nothing else is covering a partial failure; the gastroenterologist read the same fact as an argument for the more standardized product, on the grounds that a plan with no backup is exactly when procedural and donor variability matter most. Neither conceded, and the disagreement will resurface unchanged if there is a fourth recurrence.