C difficile: A Change in First-Line Treatment and New Biologic Agent

Neil Skolnik, MD


July 06, 2021

This transcript has been edited for clarity.

I'm Dr Neil Skolnik. Today we are going to talk about the Infectious Diseases Society of America's (IDSA's) 2021 Guidelines on Management of Clostridioides difficile Infection in Adults. There are some critically important changes to know about.

Fidaxomicin as First Line

Very simply and clearly, fidaxomicin is now recommended as the preferred agent for Clostridioides difficile infection (CDI) over vancomycin. Remember, in 2017 the IDSA guidelines recommended using vancomycin over metronidazole (Flagyl). The 2021 guideline suggests that for an initial CDI, fidaxomicin should be used rather than vancomycin.

Note that this is a conditional recommendation.

A "conditional recommendation" means that the IDSA used the rigorous GRADE approach to evaluate the evidence. In that rubric, the words "we suggest" indicate a conditional recommendation. What this means, as they explicitly state, is that vancomycin remains an acceptable alternative. The committee recognized that the cost of fidaxomicin is much greater than vancomycin. Implementation of the recommendation for fidaxomicin will depend on local available resources.

The rationale for this recommendation is that although initial clinical responses are similar for both agents, fidaxomicin increases the rate of sustained response of CDI by 16% at 4 weeks after the end of therapy, compared with vancomycin.

The higher sustained clinical response associated with fidaxomicin may be especially beneficial in patients at the greatest risk for recurrence: individuals who are over 65 years of age, those with compromised immunity, and those with a history of CDI recurrence. The recommended treatment for fulminant CDI remains high-dose vancomycin.

For patients who have recurrent CDI episodes, the committee suggests fidaxomicin in either a standard or extended-pulsed regimen, rather than a standard course of vancomycin. This also is a conditional recommendation. A pooled subgroup analysis of patients with multiple recurrences showed that fidaxomicin, when compared with vancomycin, increased the sustained response at 30 days after treatment by 27%.

The guidelines state that vancomycin in a tapered and pulsed-dose regimen or vancomycin as a standard course are acceptable alternatives for a first CDI recurrence. For patients with multiple recurrences, we should use either fidaxomicin or vancomycin in a tapered or pulsed regimen, vancomycin followed by rifaximin, or fecal microbiota transplantation.

Role for a New Agent: Bezlotoxumab

Finally, another interesting new addition to the guidelines is the use of a monoclonal antibody against C difficile toxin: bezlotoxumab. Bezlotoxumab is given as a one-time infusion over 60 minutes and has a half-life of approximately 18 days. For patients with recurrent CDI within the past 6 months, the committee suggests using bezlotoxumab along with the recommended antibiotics rather than using antibiotics alone. This was a conditional recommendation, with very low certainty of evidence. Bezlotoxumab might also be considered in patients with a primary CDI episode and risk factors for CDI recurrence.

The rationale here? The addition of bezlotoxumab reduced CDI recurrence by almost 40% and reduced CDI-associated hospital readmission at 30 days by over 50%. The effect was greatest in those with the highest number of risk factors for recurrence. Caution must be used for bezlotoxumab in patients with congestive heart failure.

In summary, consider fidaxomicin as first-line therapy for CDI, with the greatest benefit in patients with recurrent infection and those at highest risk for recurrence. A monoclonal antibody, bezlotoxumab, is now available for the treatment of recurrent CDI and can be used along with either fidaxomicin or vancomycin to reduce the likelihood of CDI recurrence.

I'm Neil Skolnik, and this is Medscape.

Neil Skolnik, MD, is a professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University and associate director of the Family Medicine Residency Program at Abington – Jefferson Health. He has published over 350 articles, essays, poems, and op-eds in the medical and nonmedical literature, as well as four medical textbooks and a book of short stories. In addition, he is the host of the American Diabetes Association's monthly Diabetes Core Update podcast. Follow him or direct-message on Twitter: @NeilSkolnik

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