Paul G. Auwaerter, MD, discusses treatment options for recurrent C difficile, including new FDAapproved fecal microbiota products.
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TRANSCRIPT
Clostridioides difficile, or C diff for short, is a toxinbased infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Hi. I'm Paul Auwaerter with Medscape Infectious Diseases, here to talk to you about recurrent or relapsing C difficile, which can be a bedeviling problem for a subset of patients and their clinicians.

Recurrent C difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second — and always after the third — relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the socalled extended pulse method, where patients would take the drug for approximately 46 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I'm not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin due to insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C difficile toxin B. I've used it a few times. It is given as a onetime infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.

Fecal Microbiota Transplant
Today I wanted to speak more about fecal microbiota transplants (FMTs) which in recent years have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%90%. However, in the past few years, there have been some serious safety signals due to possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I'm therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I'd spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received FDA approval. It's been around for some time. It can be used in either upper or lowerGI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDAapproved products I think are worth knowing about. They've just been approved recently and we're a little uncertain of where they're going to end up in the treatment landscape.

The first is from the Ferring Corporation, and it goes by fecal microbiota, livejslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6% compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6month period.

The other product, also FDAapproved, is from the Seres Corporation. It was previously called SER109, and is now called fecal microbiota spores, livebrpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donorderived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in The New England Journal of Medicine. They showed that 12% of those taking this product had a relapse compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under$10,000 range. The first (Rebyota) is a rectal infusion; it is a oneanddone treatment but creates logistical issues. Interestingly, it could be a billable procedure for ID clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

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