Traditional FMT Is Still the Cost-Winner for Recurrent C. diff, Study Finds

Clostridioides difficile infects an estimated 460,000 Americans every year, running up more than $5.4 billion in healthcare costs, and the recurring form of the infection is where the real trouble compounds. Two FDA-approved commercial microbiome products have entered the market in recent years, raising an obvious question: are they worth the premium over the decades-old practice of fecal microbiota transplantation? A new cost-effectiveness analysis by Mehta and Hvas, published in June 2026, offers a careful answer: probably not, at current prices.

Traditional FMT outperforms commercial products on cost-effectiveness

Using a Markov model to simulate patient outcomes across multiple recurrence scenarios, Mehta and Hvas compared colonoscopy-delivered FMT head-to-head against two commercial products: live-brpk (sold as Rebyota) and live-jslm (sold as Vowst). Traditional FMT emerged as the most cost-effective strategy for preventing recurrent CDI. Antibiotic therapy alone, despite its lower cure rates, was actually modeled as more cost-effective than either commercial product at their current price points. The analysis found that FMT for a first recurrence was cost-effective 90% of the time at a willingness-to-pay threshold of $100,000 per quality-adjusted life year, a standard benchmark in health economics.

The $5.4 billion burden of recurrent C. difficile infections

The stakes behind these numbers are real. The economic burden of recurrent C. difficile adds an estimated $15,000 to $60,000 per patient on top of initial infection costs, making treatment choice a genuinely consequential financial decision for hospitals and payers. Recurrent CDI spirals: each episode raises the risk of another, and patients who have suffered two or more recurrences face relapse rates that render standard antibiotic therapy nearly futile on its own. This is the population the Mehta-Hvas model specifically targeted, patients with two or more prior recurrences facing a decision about next-line therapy.

FMT cure rates of 70 to 91% versus 23 to 62% for standard therapy

The efficacy case for FMT has been building for years. A systematic review and meta-analysis of FMT versus antibiotic therapy found recurrence rates of 16% for FMT patients compared to 42% for those on standard antibiotic therapy, a gap that makes the biological argument straightforward. The Mehta-Hvas analysis draws on comparable figures: FMT cure rates ranging from 70 to 91%, versus 23 to 62% for standard therapy. Donor-derived FMT specifically showed substantially greater benefit than autologous transplant, with cure rates of 90.9% against 62.5%, underscoring that the therapeutic effect comes from introducing a healthy donor microbiome rather than simply resetting the patient's own.

The optimal treatment pathway the model identified has a clear logic to it. Fidaxomicin for initial non-severe CDI. Vancomycin for initial severe CDI. FMT for first and subsequent recurrences. Safety data supported this sequence: FMT's adverse events are mostly mild and gastrointestinal, and no increased long-term risk appeared in follow-up extending to five years.

Markov modeling and its limits for comparing CDI strategies

A Markov model works by assigning patients to discrete health states (active infection, recurrence, cure, death) and simulating transitions between them over time, with probabilities and costs attached to each move. This kind of cost-effectiveness analysis is the standard tool for comparing interventions when you cannot run a head-to-head randomized trial across every relevant scenario. Mehta and Hvas ran multiple sensitivity analyses to stress-test their conclusions under different assumptions.

The model has real constraints. Colonoscopy-delivered FMT is not always an accessible option: infrastructure requirements, specialist availability, and patient tolerance for the procedure vary considerably. The route of administration matters too. Studies comparing capsule-delivered FMT to colonoscopy show variable results, and using fresh versus frozen donor material introduces further heterogeneity into the evidence base. These factors make it difficult to generalize the model's cost inputs cleanly to every clinical setting.

Commercial FMT products and the pricing question

The arrival of FDA-approved products like Rebyota and Vowst, alongside American Gastroenterological Association guidelines recommending FMT-related therapies for most recurrent CDI patients, has reshaped the clinical landscape. The Mehta-Hvas analysis does not argue against these products on efficacy grounds. It argues against them on value grounds, at their current prices. If manufacturers reduced prices or if real-world effectiveness data proved superior to what the model assumed, the calculus could shift.

For Canadian hospitals specifically, the analysis found that establishing a dedicated FMT unit becomes cost-effective once it treats between 15 and 47 eligible patients annually, a threshold that many regional centers could plausibly meet. That finding points toward investment in traditional FMT infrastructure as a near-term lever, rather than waiting for commercial product prices to fall.

What remains genuinely open is how the evidence will evolve as post-market data accumulates for Rebyota and Vowst. The Markov model is only as good as the inputs it uses, and the commercial products are newer, with thinner long-term datasets. If those products demonstrate durable superiority in hard-to-treat populations, a future cost-effectiveness analysis may reach different conclusions. For now, the traditional approach holds its ground.

Evidence rating

EMERGING — 80/100

Caveats:

• This is a modeling study (Markov model), not a clinical trial — findings depend on the assumptions built into the model rather than direct patient observation.
• Funding source was not disclosed by the authors.
• FMT by colonoscopy may not be accessible in all clinical settings, and results may vary by administration route (capsule vs. colonoscopy) and donor material (fresh vs. frozen).
• Cost-effectiveness conclusions are sensitive to pricing of commercial products, which may change as the market evolves.

Markov decision-analytic model synthesizing RCT and observational efficacy data to compare cost-effectiveness of colonoscopy-delivered FMT versus commercial microbiome products (live-brpk, live-jslm) and antibiotic regimens for recurrent C. difficile. The model approach introduces assumptions that may not generalize across all clinical settings, and findings have not been validated in an independent modeling or prospective study. Funding was not declared by the authors.