December 2, 2022

Administration Strategies and Treatment Guidelines


James A. McKinnell, MD: At times, infectious disease physicians become, I would say, creative in how we approach certain issues. There’s a lot of treatments we’re trying: long-term vancomycin, those 6-8 week tapers, rifaximin chasers. There is a lot in this space. How do you, as microbiome experts, react to that? What does it mean from a strategic approach to C diff [Clostridioides difficile]?

Carl V. Crawford, MD: The antibiotic we use with the narrowest spectrum is the preferred agent due to the pathophysiology of this particular infection. I tend to use longer antibiotic treatments in people who don’t have access to another treatment that we can use later as a cure. We can talk about that in a moment. I use extended courses probably as a second line after an initial course of fidaxomicin or an initial course of vancomycin has failed. But the more antibiotics we use in individuals, the greater the collateral damage we cause to the system. I try to limit the amount of antibiotics I use unless it’s fidaxomicin because it’s so narrow spectrum you can continuously suppress the C diff and hope your rainforest starts growing around it.

James A. McKinnell, MD: The consensus is the idea that we want to use fidaxomicin perhaps with this extended treatment, going from 5 days of full dose treatment twice a day to twice a day, every other day.

Kelly R. Reveles, PharmD, PhD, BCPS: Potentially. This is where we have good data. Going back to why we even do this, when we scale back these antibiotic therapies, there’s a two-pronged approach. These antibiotic-free days begin to allow the normal gut microbiome to restore itself. At the same time, you may have some remaining spore seeds in the gut that will germinate. Antibiotics don’t kill the spore phase, so you want it to germinate so you can eliminate it once you redose those antibiotics.

James A. McKinnell, MD: We have described fidaxomicin as our selective weed killer. I want to tackle a subject that is interesting because I have trouble with the instructions. When I look at the guidelines on antibiotics, they’re somewhere out of date, they’re changing; there are several versions. Kelly, you’re our guideline expert. What do you think of the IDSA? [Infectious Diseases Society of America] recent guidelines and changes?

Kelly R. Reveles, PharmD, PhD, BCPS: I really enjoyed the ideas they came up with. We had a very comprehensive, comprehensive, and beautiful guideline published in 2018, but since then we’ve had additional studies that favor, for example, fidaxomicin over oral vancomycin. Rather, what they did was a targeted update with this new guideline where they just addressed those initial antibiotic therapies based on the new data. This is something the IDSA is pushing more these days: increasing the speed at which new guidelines are released so that we have more up-to-date advice on how to treat these patients.

Sahil Khanna, MBBS, MS: Kelly, right before I came to Vegas [Las Vegas, Nevada] for our meeting [American College of Gastroenterology Annual Scientific Meeting], the European directives are out. It’s been a remarkable year for C diff. We received the GI American College of Gastroenterology guidelines, an update on the IDSA guidelines, and the European guidelines are out. With the guidelines in 2010 and 2013, we used something for the first time, it didn’t work, we used the same thing for the second time. We walked away from that. We have become much smarter. I’m using something for the first time, it doesn’t work, I’m using something different. It’s like basic physiology how I think about it.

What the European guidelines did was different is they tried to figure out who should get fidaxomicin or vancomycin just because of availability and cost issues, and they talk about people at higher risk high rate of recurrence, increasing age, serious illness, and history of hospitalization of C diff. The other thing that the guidelines have done very well is try to implement recurrence prevention strategies from the outset. C diff is not a workaround for this bug [with which you] go home and everything will be fine. It’s about dealing with this bug and thinking about strategies to prevent its reappearance. The guidelines incorporate immune-boosting strategies such as intravenous bezlotoxumab from the outset if you are at higher risk of recurrence and also in a selected patient population. All the guidelines are integrated, which is good for us so that we can then use them to get these drugs approved.

James A. McKinnell, MD: Thanks for watching this Pharmacy hours® Peer exchange. If you liked the content, please sign up for our email newsletters to receive the next ones. Peer exchanges and other great content straight to your inbox.

Transcript edited for clarity.