Expert Perspectives on Advances in the Management of C. Difficile - Episode 17

Making Strides in the Management of C. Difficile

Peter L. Salgo, MD: What’s interesting to me is we’ve been talking about some fairly cutting-edge stuff; whether it’s biologics, new antibiotics, or commercially available fecal transplants. What else is in the pipeline that’s really exciting? Is there something else out there that we should be looking for?

Dale N. Gerding, MD: There are a couple of things. Paul Feuerstadt, MD, FACG, AGAF has already mentioned the upcoming likely FMT [fecal microbiota transplantation] result publications and perhaps even FDA [Food and Drug Administration] approvals in the next year. There is also a vaccine out there that has completed its trial and we’re awaiting the results. This vaccine could give us an idea of whether we will have a vaccine for prevention of C diff [Clostridioides difficile] infection in the future, and I’m looking forward to seeing that in the upcoming year. I’m also interested in something called nontoxigenic C diff, which in this case, rather than replace the microbiome, we would replace the organism. Instead of toxigenic C diff, you replace it with nontoxigenic C diff by giving it orally as a sporiform. It has all the same properties the C diff has that’s toxigenic, but it’s harmless because it lacks all the toxins.

Peter L. Salgo, MD: That’s really elegant. That’s cool.

Dale N. Gerding, MD: That has just been acquired by Destiny Pharma in the UK [United Kingdom]. They will be developing it going forward.

Peter L. Salgo, MD: This is really exciting stuff. Before we wrap up, what I’d like to do is give each of you an opportunity to give one closing statement. We’re going to go around the horn, so to speak. Teena Chopra, MD, MPH, why don’t you start.

Teena Chopra, MD, MPH: Sure. At this point, since we are in the midst of the COVID-19 pandemic, we should not forget that COVID can also present with diarrhea and as well as C diff. At Wayne State University, we recently published an article in Emerging Infectious Diseases where we presented a case series of 9 patients that had both COVID and C diff together. Thinking about C diff, it is extremely important when patients present with diarrhea. Of these 9 patients, 4 of them ended up dying, 2 of them went to long-term care facilities, and the other 2 ended up going to hospice. They had very poor outcomes and this is something that I wanted to highlight at this point.

Peter L. Salgo, MD: Paul Feuerstadt, MD, FACG, AGAF?

Paul Feuerstadt, MD, FACG, AGAF: It is such an exciting time in the world of C diff. We’re seeing changes in epidemiology and we are shifting from a predominantly healthcare-associated infection to about a 50/50 community versus healthcare. A lot of that resulted from educational symposia like this where individuals at their local institutions are understanding better ways of managing C diff, better ways of avoiding C diff in the hospital, better infection control, antimicrobial stewardship, more aggressive therapy, and understanding the cutting edge. My excitement towards this really focuses, on fidaxomicin originally, and bezlotoxumab.

Now looking forward, things like what Dale Gerding, MD mentioned before about nontoxigenic C difficile to treat this, commercially available microbiota replacement like RBX2660 and also the vaccine. The vaccine could be a game-changer. If we shut C diff down before the patients actually develop it, that would be huge. During 2021 and 2022, I think will be an exciting time as a clinician and somebody who’s interested in C difficile. It’s my job to put myself out of business and hopefully get really great treatments for these patients, so that we don’t have to talk about recurrent C difficile.

Peter L. Salgo, MD: Dale Gerding, MD, you’re up.

Dale N. Gerding, MD: I would like to just echo what Paul Feuerstadt, MD, FACG, AGAF said. The tendency with management of C diff is now around prevention. We’ve heard about fidaxomicin, bezlotoxumab, FMT [fecal microbiota transplantation] all preventing recurrence, now we’re going to see a vaccine that’s hopefully going to be a primary preventive. If nontoxigenic C diff is effective, it will be used to prevent not only recurrence but also primary prevention by giving it to people while they take antibiotics that are at high risk. I think prevention is the buy word of the future for C diff management.

Peter L. Salgo, MD: Tom Lodise, PharmD, PhD?

Thomas Lodise, PharmD, PhD: I’m excited about the therapies as well, but I would like to stop the problem before it even occurs. Whenever I think about stewardship, the primary reason is to prevent CDI [Clostridioides difficile infection]. Every day matters. I think the studies are clear. The longer you use antibiotics, the more likely you increase the risk that persists for a month, if not 3 months. The 1 question we’ve been asking a lot is, “Do you need that drug? Do you need it for 2 days, 3 days?” Every day you continue that drug you escalate risk. Many times, we treat ourselves rather than our patients. These shorter course therapies, moving to thinking about less use of quinolones, particularly in the outpatient setting. Even though we have a slightly different etiology there, a lot of it is driven by antibiotic use in colonized individuals.

If the 1 thing I can say is Paul Feuerstadt, MD, FACG, AGAF: I’m glad to hear that you’re going to be put out of business, but I would like to put you out of business by more judicious antibiotic use. Hopefully, we’re making strides because CDI is a chronic disease. I think we can be better, and I think 1 of the ways we can be better is not only with therapy selection but with how we use antibiotics in general.

Peter L. Salgo, MD: Joe Reilly, BS, PharmD, BCGP, you’ve got the last word.

Joseph Reilly, BS, PharmD, BCGP: I’m really looking forward to seeing where FMT takes us and products that come out soon. The impact of these products on recurring CDI is so dramatic. We’re talking about following patients out to a year and it’s still 80% effective; patients that are normally excluded from studies like those with IBD [inflammatory bowel disease]; durability of treatment where it lasts. Normally, where would these patients end up? I would assume that most of them wouldn’t even be alive at the time they’re going to be evaluated because of their recurrences and each time associated with mortality and a hospital admission that leads to further problems. I think FMT in our immediate future is very promising and hopefully it will be moved a little bit up to the forefront of treatment in patients with CDI. I know looking back at the data, it might seem like the Wild West, where it was colonoscopy, endoscopy, sometimes a coffee can was involved. Now that we have regulated products by the FDA that are screened to look for resistant bacteria—MRSA [Methicillin-resistant Staphylococcus aureus], VRE [vancomycin-resistant enterococci], and such—I imagine that safety will really help get these products used more often.

Peter L. Salgo, MD: I want to thank everybody. I can remember, as I told you, Teena Chopra, MD, MPH, we did one fecal transplant which was remarkable. We had to go find a hospital in the city that was making their own, I don’t want to use the word cocktail but I will, their own proprietary preparation.

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Transcript Edited for Clarity