M Fischer et al. Clin Gastroenterol Hepatol 2026; 24: 2359-2369. AGA Clinical Practice Update on Management of Clostridioides difficile Infection in Adults: Expert Review

This article provides 14 “Best Practice Advice” statements. Since this is geared to adults, some are not applicable for the pediatric age group. I have highlighted five of them:

• #4: Fidaxomicin (200 mg twice daily oral for 10 days) is a narrower spectrum agent, and given lower recurrence rates, is favored as first-line therapy for nonfulminant C difficile infection. However, given practical considerations, vancomycin (125 mg 4 times daily oral for 10 days) is also acceptable therapy. Metronidazole should not be used outside of fulminant disease.
• #6: Following treatment of C difficile infection, clinicians should not perform routine test of cure. Stool testing should only be performed for persistent worsening of diarrheal symptoms.
• #9: Prolonged, low dose, suppressive vancomycin regimen (125 mg daily) for secondary prophylaxis may be considered in patients with multiple recurrent episodes who are not candidates for fecal microbiota-based therapies due to ongoing comorbidities, limited life expectancy, or ongoing/frequent systemic antibiotics or who have failed multiple courses of fecal microbiota-based therapy.
• #10: Fulminant C difficile infection should be managed by a multidisciplinary team (gastroenterology/infectious disease, surgery, medicine/critical care) and treated with high-dose vancomycin 500 mg every 6 hours (oral or enteral), with metronidazole 500 mg intravenously every 8 hours, and if ileus is present, rectal vancomycin 500 mg every 6 hours should be added.
• #12: Use of vancomycin is not advised during systemic antibiotic administration to prevent C difficile infection. Probiotics are not advised to prevent an initial or recurrent C difficile infection. To promote restoration of healthy gut microbiota, patients should be instructed to consume a healthy diet including a variety of fruits and vegetables, rich in both soluble and insoluble fiber. ” Although some guidelines suggest OVP in high-risk patients, these recommendations were conditional and based on low-quality evidence.²⁰“

For recurrent CDI, “experts recommend treating a first recurrence with an agent different from that used initially.” One option discussed by authors and in the treatment algorithms (Figure 2) includes use of a vancomycin taper. After a course of vancomycin 125 mg QID x 14 days, a typical taper would be BID x 14 days, then daily x 14 days, then every 3rd day x 14 days. An alternative is a fidaxomicin EXTEND (200 mg BID days 1-5, then every other day, days 7-25 days.

My take: This is a useful reminder of current best practices for C diff infection (in adults). Updated guidelines in pediatrics would be helpful.

Related blog posts:

• Dr. Stacy Kahn: Clostridioides difficile 2026
• AGA Clinical Practice Update:  Clostridioides difficile Infection in Inflammatory Bowel Disease
• Discordant Clostridiodes difficile Testing In Patients with Inflammatory Bowel Disease
• Breaking Down the New mRNA Vaccine for C. difficile
• Clostridioides difficile Treatment in 2026
• Fidaxomicin Treatment of Clostridioides difficile in Children and Adolescents
• C difficile three-fer: Overdiagnosis with Multiplex Testing, Fidaxomicin Pediatric Approval, & Changing Incidence
• “Diagnostic Stewardship” –Reducing Unnecessary Clostridioides difficile Treatment by Changing Testing Approach (2024)
• OpenBiome Suspending FMT Shipments (2024)
• ACG Clostridium Difficile Guidelines Plus One (2021)

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