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Why I Favor Treatments That Prevent Recurrence of Clostridioides Difficile Infection

Paul Feuerstadt, MD, FACG, AGAF

Assistant Clinical Professor of Medicine
Attending Gastroenterologist

Department of Gastroenterology
Yale University School of Medicine
PACT-Gastroenterology Center
Hamden, Connecticut

Paul Feuerstadt, MD, FACG, AGAF, has disclosed that he has received funds for speakers bureau participation from Ferring, Merck, and Takeda; consulting fees from Ferring; and funds for advisory board participation from Ferring and Takeda.

View ClinicalThoughts from this Author

Released: February 11, 2022

For some time, I have favored treatments that minimize the risk of Clostridioides difficile infection (CDI) recurrence, and this approach is now consistent with the current 2021 Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) guidelines. Specifically, I have favored fidaxomicin over vancomycin, largely phased out treatments such as metronidazole, incorporated bezlotoxumab for patients at greater risk for recurrence, and included fecal microbiota transplantation for patients with either 3 episodes of CDI or ≥2 recurrences. Therefore, for me personally, the 2021 guideline updates validated what I had been doing previously, and I am hopeful that this update will motivate others to do the same.

Considering the Risks
I believe the most important elements to consider regarding the management of initial and recurrent CDI are risk factors. Risk factors include age older than 65 years, any form of immune compromise (eg, chronic kidney disease, HIV, and inflammatory bowel disease), medication exposures (eg, antimicrobials, proton pump inhibitors, and histamine blockers), whether patients live and spend significant amounts of time in skilled nursing facilities or hospitals, and whether patients have a hypervirulent strain.

Considering and contextualizing these risk factors can help with triage and choosing between fidaxomicin and vancomycin. Because fidaxomicin is associated with lower rates of recurrence, this agent is a better choice for patients at increased risk for recurrence. For me, ≥2 risk factors for recurrence cement the need for fidaxomicin—especially the core risk factor of age older than 65 years plus 1 other risk factor—but I also think we should preferentially use fidaxomicin for initial treatment. European Society of Clinical Microbiology and Infectious Diseases guidelines also recommend the initial use of fidaxomicin because it is a narrow-spectrum antibiotic, so it has minimal effect on the surrounding microbiota, and it decreases the collateral damage from the treatment of C difficile, therefore reducing associated rates of recurrence.

With ≥2 risk factors for recurrence present, I also would strongly consider using bezlotoxumab to further reduce the rate of recurrence and break that vicious cycle in which patients can ultimately get caught. Since the publication of the updated IDSA/SHEA guidelines in September 2021, what has really been exciting for me is seeing more patients coming to clinic having received bezlotoxumab and fidaxomicin. Seeing patients who have failed certain treatments is challenging, but I know that with more patients receiving appropriate therapies earlier in the treatment course, fewer will end up in the cycle of refractory and recurrent disease—and that means patients will have better outcomes.

Real-world Data in Support of the Updated Guidelines
I often am asked about the data supporting the use of fidaxomicin earlier in the treatment algorithm—for both initial infection and for recurrent infection—and the data behind bezlotoxumab. Although I do explain the pivotal phase III trials, my colleagues want to know that there are real-world data and that the trial results have been validated in this setting.

Therefore, I frequently cite a study by Goldenberg and colleagues that assessed real-world experience with fidaxomicin in Britain. This trial looked at recurrence rates 1 year before and 1 year after fidaxomicin use. Despite the various healthcare systems using fidaxomicin in different ways, each healthcare system showed a statistically significant reduction in recurrence rates.

We also have recent real-world data considering bezlotoxumab. Although it is recommended to administer this agent within approximately 1 week of initiating antimicrobial therapy, Westman and colleagues presented real-world data at the American College of Gastroenterology 2021 meeting showing that bezlotoxumab infused within 48 hours of receiving the final dose of antibiotic for recurrent CDI was effective at reducing rates of recurrence.

Data From IDWeek 2021 in Support of the Updated Guidelines
The 2017 IDSA CDI guidelines update included recommendations to phase out metronidazole as a preferred antibiotic in favor of either fidaxomicin or vancomycin for first-line treatment of CDI. At IDWeek 2021, Dubberke and colleagues compared the prescribing patterns of a Medicare population (older than 65 years of age) the year before the 2017 guidelines were issued vs the year after the guidelines were issued and found that healthcare professionals were following the guidelines, as evidenced by the change in prescribing patterns showing that the use of metronidazole plummeted while vancomycin use skyrocketed.

Unfortunately, the investigators found that CDI recurrence rates were slightly increased at 4 weeks (P = .001) and at 8 weeks (P <.0001) pre vs post guideline update, possibly because vancomycin did not elicit meaningfully improved outcomes compared with metronidazole. Although uncommonly used, fidaxomicin demonstrated superior recurrence and sustained recurrence rates compared with either vancomycin or metronidazole. The study by Dubberke and colleagues therefore validates that fidaxomicin should be the preferred therapy, as it is associated with reduced rates of recurrence and less effect on the microbiota when patients are receiving treatment, and therefore patients are more likely to eradicate the spore phase and have improved outcomes.

I think the most important concept addressed in the updated guidelines is the focus on reducing future recurrence. Knowing the risk factors for recurrence and triaging patients with the greatest risk will give practitioners the best opportunity to target therapy to those at greatest risk, reduce future recurrence, and avoid the cycle of repeating recurrences. Of importance, treatment of initial infection is our best opportunity to avoid that cycle because, at that point, patients’ microbiota are depleted but not yet devastated.

Your Thoughts?
In your practice, have you changed how you manage your patients with initial CDI? Join the conversation by posting in the discussion section.

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