Selecting Therapy to Treat C. Difficile


Important factors to consider when selecting an appropriate therapy to treat C. difficile.

Peter L. Salgo, MD: Let me back up for a minute and take the 10,000-foot view.… What is it that makes this organism so difficult to treat? You get pneumococcal pneumonia [Streptococcus pneumoniae] and the odds are you can give an antibiotic, you’re going to get a response, and you hope it doesn’t come back. I know there are spores here. Is that it? Is there something other than what is obvious to me about a CDI [Clostridioides difficile infection] that is so unique that makes it so hard to treat? Paul?

Paul Feuerstadt, MD, FACG, AGAF: That’s an excellent question. The challenge really emanates in the fact that we’re trying to do 2 things at once usually when we think about the treatment of C difficile [Clostridioides difficile]; we’re trying to suppress the organism but we’re also trying to restore the microbiota. There are 2 approaches that I think about with the management of C difficile: 1. I think about attacking the bacteria. Those are your antimicrobials: vancomycin [Vancocin], fidaxomicin [Dificid], perhaps metronidazole, although that’s falling out of favor, then 2., there’s boosting our immune system. Our immune system can take the form of 2 things: 1. It could be our bloodborne immune system, and we could do the product called bezlotoxumab, which is a fully humanized monoclonal antibody to toxin B that is given as a 1-time infusion that’s associated with reduced rates of recurrence, or 2. we can boost our microbiota with microbiota restoration therapy.

The way that I think about treating C difficile is, honestly, a little bit like raising a child. The first 18, 21 years of that child’s life we provide food, shelter, clothing, quite a warm environment for those kids; that’s the antimicrobial phase. We are suppressing the infection but we’re not necessarily completely wiping it out. Once we pull that antimicrobial off and that antimicrobial course ends, it’s up to our colonization resistance or our microbial to give C difficile that knockout punch. However, if the microbial takes a hit from another antimicrobial, it’s much more likely to recur, up to about 48% to 50% of the time.

If we envision a microbial restoration therapy, or fecal transplant as reinforcing the healthy gut flora in the process of giving C difficile the knockout punch, you’re basically enhancing that knockout punch and decreasing the likelihood for recurrence. However, if therapies are not available, or the patients don’t receive a fecal transplant, this is the concept behind that. Most patients who receive either fidaxomicin or vancomycin will respond and will get better. What we’re talking about with other therapies are those subgroups that are at greater risk: aged over 65, history of immune suppression, history of C difficile, the NAP1/B1/027 strain, severe infection, patients on PPIs [proton pump inhibitors], patients who received concomitant antimicrobials. Those are the individuals that we’re really focusing on and better understanding how we get rid of this.

Peter L. Salgo, MD: You want to evaluate all that in somebody with Clostridioides difficile in terms of your initial therapy. I’m not sure I agree with the child-raising metaphor with Clostridioides difficile, but that’s OK.

Paul Feuerstadt, MD, FACG, AGAF: The concept here is that when we approach a patient with Clostridioides difficile, with an initial episode or even recurrence, it’s thinking about their entire clinical gestalt. It’s thinking about whether they have severe infection, whether they have community versus health care, health care-associated infection, worsened outcomes, those who are more likely to need a more aggressive therapy, multiple risk factors for recurrence, those who are more likely to have an adverse outcome, therefore more likely to need an aggressive therapy, then of course severe disease. White cell count [white blood cell count] greater than 15,000 in the updated 2018 IDSA/SHEA [Infectious Diseases Society of America/Society for Healthcare Epidemiology of America] guidelines; creatinine greater than 1.5 mg/dL [milligrams per deciliter]. Those simple things—severity, health care versus community associated—that’s what guides our therapy.

In my mind, what we’re trying to do is pre the IDWeek update from a couple of weeks ago. Deciding between vancomycin and fidaxomicin to me really boiled down to those factors and risk factors for occurrence. Fidaxomicin’s sweet spot is that it is associated with statistically significant reduction and rates of recurrence. Patients who have multiple high-risk factors for recurrence would benefit from that product. Now, the IDSA/SHEA looked at 2 other pivotal studies and found that fidaxomicin was superior to vancomycin. They made the recommendation that fidaxomicin should be used preferentially, and that was a moderate level of evidence for initial infection and a low level of evidence for recurrence. One important point: in the recurrent group they recommended either 200 mg twice daily for 10 days, or 200 mg twice daily for 5 days, and then 1 tablet every other day—days 7 through 25. That was associated with a remarkably low recurrence rate of about 6.2% at 90 days, which was impressive when you’re talking about 25% recurrence rates of a standard vancomycin course.

Peter L. Salgo, MD: If you enjoyed this content, you should subscribe. We have an e-newsletter, and you can receive upcoming Peer Exchanges and other great content in your inbox—that’s right, electronically. I’ll see you next time. I’m Dr Peter Salgo. Thanks again for watching.

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