The American Gastroenterological Association (AGA) recently released guidance focusing on Clostridioides difficile (C difficile) infection management. The AGA clinical practice update, Management of Clostridioides difficile Infection in Adults, features 14 best practice advice statements that provide guidance on the prevention of C difficile infection, including guidance on classification, first-line therapy options, managing recurrence, and more. 

The AGA specifically designates the management of C difficile infection as a topic of high clinical importance. The disease affects more than 360,000 patients in the United States annually. The purpose of this AGA clinical practice update is to provide evidence-based advice to clinicians with patients who have or may have C difficile infection.

For a complete look at all fourteen best practice statements and their associated rationale, view the full-text version of the AGA clinical practice update.

Key Best Practice Statements from the 2026 AGA Clostridioides difficile Infection Clinical Practice Update:
  • Clinicians should classify hospitalized patients with C difficile infection as having nonsevere, severe, or fulminant disease at diagnosis. White blood cell count >15,000 cells/uL and/or creatinine >1.5 × baseline are indicative of severe C difficile infection and increased risk for recurrence and poor outcomes. Patients with additional findings of shock, ileus, or megacolon have fulminant C difficile infection, which can be fatal. 
  • 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.
  • First C difficile infection recurrence (second episode) within eight weeks of completing anti–C difficile infection therapy should be treated with either a tapering course of vancomycin or fidaxomicin. Treatment of C difficile infection should include a risk assessment for C difficile infection recurrence and consideration of microbiota restoration therapy to prevent recurrence
  • Fecal microbiota-based therapies (fecal microbiota spores, live-brpk, fecal microbiota, live-jslm, or conventional fecal microbiota transplant) should be offered after treatment of a second recurrence (third C difficile infection episode). Microbiota restoration therapy may be considered after treatment of an initial infection or first recurrence in patients who are at high risk for further recurrence or in patients whose initial C difficile infection episode was particularly morbid or difficult to treat. 
  • 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. 
  • 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. 
  • Individuals with a history of C difficile infection should be specifically counseled to avoid unnecessary antibiotic therapy.

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