Paul Feuerstadt, physician: How can we start treating? Clostridioides difficile optimal? Well, we can look at the guidelines. The guidelines of the Infectious Diseases Society of America – Society of Healthcare Epidemiologists of America were updated in 2021. Bincy, can you explain to us what the recommendations were for the treatment of a first episode of C difference?
Bincy Abraham, MD, MS: Yes. Per guidelines for the initial C difference infection, it is recommended to use fidaxomicin instead of vancomycin. They say this with moderate certainty based on the data, but that assumes we have the resources to be able to use fidaxomicin, because sometimes it’s not available. It is not on the form at the hospital, or not available, or too expensive for the patient to get from their insurance, so they do say that vancomycin is an acceptable alternative.
Paul Feuerstadt, physician: Excellent. Is metronidazole really coming into the picture? Bincy, you said before that in the IBD [inflammatory bowel disease] population, the answer is no. In general, I can say that the answer is largely no. The recommendation was to use metronidazole if nothing else is available, if the white blood cell count is less than 15,000 and the creatine is less than 1.5 mg/dL. Metronidazole has largely been phased out of the treatment algorithm. Teena, can you tell us what the recommendations were for a second episode or first rerun?
Teena Chopra, MD, MPH: Secure. If vancomycin was initially used for the first episode, there is a strong recommendation to use fidaxomicin for the first recurrence. If fidaxomicin was used in the first episode, you can use pulsed or tapered vancomycin. That is one of the recommendations for a recurrence.
Paul Feuerstadt, physician: Excellent. Tom, what about the third episode and after, or the second rerun and after?
Thomas Lodise, PharmD, PhD: Paul, fidaxomicin again. Looking at those recurrent episodes, it’s a conditional recommendation with low certainty of evidence, but I found the data quite compelling for the recommendation of fidaxomicin, as Teena mentioned, as a standard or extended pulse regimen. You’re looking through all of his randomized trials. The absolute difference in sustained response after 30 days was significantly different. Again, it was a small subset, but directionally we saw that in 90 days as well. Whenever I look at these absolute differences, Paul, I always convert them to a number to be treated. For every 10 patients you treat with fidaxomicin, with these third episodes and beyond, you get another cure. We think about the long-term consequences; the emotional, physical and mental well-being or the toll that C difference attracts these patients. For me it’s worth it. We look at these economic studies that look at quality-adjusted shares of life and the cost of an annual profit; they are all considered reasonable therapies. They also state within the guidelines that vancomycin predictably also results in a successful initial cure, even [in] patients with recurrent infections. They still offer some possibilities, vancomycin in patients, for some of the reasons Bincy mentioned, [as] if there are insurance issues. But I would argue that patients should be given the best medicine. The cost of a recurrence is $25,000, the complications are $50,000. Again, think about the numbers needed to treat fidaxomicin use; avoiding all those downstream consequences, I think, offers a lot of value to our patients.
Paul Feuerstadt, physician: I tend to agree. I think there are some important points here. First, the IDSA-SHEA guidelines used a PICO analysis (population, intervention, comparison, outcome). This was really a largely statistical analysis. Tom, you’ve done a good job bringing it back to reality, which is a number to deal with. There are a few 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 antimicrobial agent. It’s a one-time infusion and there’s really compelling data behind it between 2 clinical trials, the MODIFY I (NCT01241552) and MODIFY II (NCT01513239) trials. In all those clinical trials, the number that needed to be treated was 10 to reduce 1 recurrence overall, but more importantly, in that population over 65 years of age, that population that we see the most C difference in the clinical trials in a predefined analysis, the number needed to treat was 6. That’s compelling data to say, “Hey, you know what, bezlotoxumab should be considered in patients at high risk of recurrence. ” Within the guidelines, they recommended it for patients at high risk of recurrence, with a first recurrence or second recurrence, and afterward if they haven’t received it once. Now it has an extended half-life, with a half-life of 19 days, so it stays in the patient systems in significant amounts for about 90 days. Well, those 90 days is usually the time we spend following up on assessing patients for future recurrence. As we switched, however, we were now talking about antimicrobials, which treat the vegetative phase. We talked about bezlotoxumab, which essentially binds toxin B and reduces the inflammatory response, but we have that black box, that dysbiotic state, that second piece we need to be healthy to reduce future recurrence.
Transcript edited for clarity