Emerging Treatment Options for Recurrent C. Difficile Infection - Episode 10

Treatment Options for C. difficile Infection (CDI)

September 14, 2022
Paul Feuerstadt, MD

Thomas Lodise, PharmD, PhD

Teena Chopra, MD, MPH

Bincy Abraham, MD, MS

Experts review treatment options for first, second and recurring episodes of C. difficile infection (CDI).

Paul Feuerstadt, MD: How can we go about treating Clostridioides difficile optimally? Well, we can lookat the guidelines. The Infectious Diseases Society of America—Society of Healthcare Epidemiologists of America guidelines were updated in 2021. Bincy, can you walk us through what the recommendations were for treatment of a first episode of C diff?

Bincy Abraham, MD, MS: Yes. Per guidelines for the initial C diff infection, it’s recommended to use fidaxomicin instead of vancomycin. They say this with moderate certainty based on the data, but that’s assuming we have the resources to be able to use fidaxomicin, because sometimes it’s not available. It’s not on formulary in the hospital, or unavailable, or too expensive for the patient to get from their insurance, so they do say that vancomycin is an acceptable alternative.

Paul Feuerstadt, MD: Excellent. Does metronidazole really enter the picture any longer? Bincy, you had mentioned earlier that in the IBD [inflammatory bowel disease] population, the answer is no. I can say generally the answer is largely no. The recommendation was to use metronidazole if nothing else is available, if the white cell count is less than 15,000 and the creatine is less than 1.5 mg/dL. Metronidazole has been largely phased out of the treatment algorithm. Teena, can you walk us through what the recommendations were for a second episode or first recurrence?

Teena Chopra, MD, MPH: Sure. If vancomycin was used initially for the first episode, there is a strong recommendation to use fidaxomicin for the first recurrence. If fidaxomicin was used in the first episode, then either you can use pulsed or tapered vancomycin. That is one of the recommendations for a recurrence.

Paul Feuerstadt, MD: Excellent. Tom, what about third episode and beyond, or second recurrence and beyond?

Thomas Lodise, PharmD, PhD: Paul, fidaxomicin again. Looking at those recurrent episodes, it’s a conditional recommendation with low certainty of evidence, but I’ve found data rather compelling for the recommendation of fidaxomicin, as Teena mentioned, as either standard or extended pulse regimen. You look across all its randomized trials. The absolute difference in sustained response at 30 days was significantly different. Again, it was a small subset, but directionally, we saw that in 90 days as well. Anytime I look at these absolute differences, Paul, I always convert them to a number needed to treat. For every 10 patients you treat with fidaxomicin, with these third episodes and beyond, you’re going to gain one more cure. We think about the long-term consequences; the emotional, physical, and mental well-being or tolls that C diff puts on these patients. To me, it’s worth it. We look at these economic studies that look at quality-adjusted life shares and the cost of a year gain; they’re all considered reasonable therapies. Also, they do state within the guidelines, vancomycin also predictably results in a successful initial cure, even [in] patients with recurrent infections. They still provide some opportunities, vancomycin in patients, for some of the reasons that Bincy mentioned, [as] if there’s insurance concerns. But I would argue patients should get the best drug. The cost of recurrence is $25,000, the complications is $50,000. Again, think about those numbers needed to treat use of fidaxomicin; avoiding all those downstream consequences, I think, provides a lot of value for our patients.

Paul Feuerstadt, MD: I tend to agree. I think there’s several important points here. First is that the IDSA—SHEA guidelines used a PICO (population, intervention, comparison, outcome) analysis. This was really a largely statistical analysis. Tom, you did a nice job of boiling it down to the reality, which is number needed to treat. There are a couple of concepts here. One, fidaxomicin is in; two, metronidazole is largely out; and three, bezlotoxumab. What is bezlotoxumab? It is a fully humanized monoclonal antibody that is given in addition to a standard-of-care antimicrobial. It’s a one-time infusion, and it has really compelling data behind it between 2 clinical trials, the MODIFY I (NCT01241552) and MODIFY II (NCT01513239) studies. Across those clinical trials, the number needed to treat was 10 to reduce 1 recurrence overall, but importantly, in that age over 65 population, that population that we see the most C diff in, across the clinical trials in an a priori set analysis, the number needed to treat was 6. That’s compelling data to say: “Hey, you know what, bezlotoxumab should be thought of for patients at high risk for recurrence.” Within the guidelines, they recommended it for patients at high risk for recurrence, with a first recurrence or second recurrence and beyond if they haven’t received it once already. Now it does have an extended half-life, with a half-life of 19 days, so it stays within patient systems for about 90 days in appreciable quantities. Well, that 90 days is usually the time that we spend in follow-up assessing patients for future recurrence.

Transcript edited for clarity