Managing C. difficile Infection in Patients With IBD: Gastroenterology | May 2026

• Clostridioides difficile infection (CDI) remains one of the most important triggers of disease flares, hospitalization, treatment failure, colectomy, and mortality in patients with inflammatory bowel disease.
• Every patient with IBD presenting with new or worsening diarrhea should be evaluated for CDI, particularly those with colonic disease, ileal pouches, or end ileostomies.
• Symptoms alone cannot reliably distinguish CDI from an IBD flare, making stool testing essential.
• The AGA recommends a multistep toxin-based diagnostic algorithm rather than PCR alone, because asymptomatic C. difficile colonization is common in IBD.
• A positive PCR without toxin detection may represent colonization rather than active infection and should be interpreted cautiously.
• Fidaxomicin is now the preferred first-line treatment for initial CDI in IBD because it reduces recurrence and preserves gut microbiota.
• Oral vancomycin remains an acceptable alternative when fidaxomicin is unavailable or cost-prohibitive.
• Metronidazole should no longer be used for CDI treatment in patients with IBD.
• Patients with severe colitis, systemic toxicity, marked leukocytosis, hemodynamic instability, or suspected sepsis should be strongly considered for hospitalization.
• One of the most important practice changes is that IBD therapy should not routinely be stopped during CDI.
• Biologics, immunomodulators, and small molecules should generally be continued when clinically indicated.
• Corticosteroids may also be initiated or continued when there is concern for concurrent moderate-to-severe IBD activity.
• If symptoms fail to improve within 48–72 hours of CDI treatment, clinicians should evaluate for:

Active IBD flare

Cytomegalovirus infection

Alternative causes of colitis

• Endoscopic assessment should be considered when uncertainty persists.
• For recurrent CDI, microbiome restoration therapies have moved to the forefront of management.
• Patients with IBD who experience at least one recurrence of CDI should be offered microbiome-based therapy, including:

FDA-approved fecal microbiota products

Fecal microbiota transplantation (where available)

• Emerging microbiome therapies demonstrate high efficacy and acceptable safety even in patients receiving immunosuppressive therapy.
• Probiotics are not recommended for either primary or secondary prevention of CDI in IBD.
• Oral vancomycin prophylaxis may be considered in selected high-risk patients with prior CDI who require systemic antibiotics.
• The update emphasizes that successful management requires simultaneous treatment of both CDI and underlying IBD rather than viewing them as competing diagnoses.

Bottom line: The major messages of the AGA 2026 update are: use fidaxomicin first-line, continue necessary IBD therapy during CDI, avoid probiotics, use toxin-based testing strategies, and strongly consider microbiome-based therapies after the first recurrence of CDI.