This expert review was commissioned by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The review was developed from expert opinion and a review of the published literature. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. The review underwent internal peer review by the Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. BEST PRACTICE ADVICE STATEMENTS BEST PRACTICE ADVICE 1: Prevention of C difficile infection should include proper barrier protection and disinfection with United States Environmental Protection Agency-approved sporicidal agents in health care settings. Patients should be counseled on the importance of handwashing and to consider disinfecting areas of the home potentially contaminated with C difficile spores, to prevent reinfection. Reassurance should be provided that C difficile infection transmission to unaffected family members is uncommon. BEST PRACTICE ADVICE 2: C difficile infection is a clinical diagnosis that requires compatible symptoms (typically acute diarrhea, following antibiotics) in combination with supportive laboratory testing. Multistep testing is preferred for best diagnostic accuracy; however, patients with discordant testing who have a high clinical suspicion for C difficile infection should be treated. BEST PRACTICE ADVICE 3: 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. BEST PRACTICE ADVICE 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. BEST PRACTICE ADVICE 5: Cholestyramine and other bile acid-binding agents should not be used as monotherapy or concurrently with oral vancomycin or fidaxomicin. Psyllium fiber can be used to bulk stools in patients who have recovered from the infection. BEST PRACTICE ADVICE 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. BEST PRACTICE ADVICE 7: First C difficile infection recurrence (second episode) within 8 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. BEST PRACTICE ADVICE 8: 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. BEST PRACTICE ADVICE 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. BEST PRACTICE ADVICE 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. BEST PRACTICE ADVICE 11: Multi-dose fecal microbiota transplantation (fresh-directed donors, or institutional stool banks) delivered via lower endoscopy, should be considered in individuals with fulminant C difficile infection. Fecal microbiota, live-jslm (Rebyota), and fecal microbiota spores, live-brpk (Vowst) have not been studied and are not approved for treatment of severe and/or fulminant C difficile infection. Due to high risk of C difficile infection recurrence, patients who recover from severe or fulminant C difficile infection should be maintained on a suppressive vancomycin regimen until a final fecal microbiota transplantation can be administered as an outpatient. BEST PRACTICE ADVICE 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. BEST PRACTICE ADVICE 13: During the treatment of C difficile infection or the prevention of its recurrence, the use of proton pump inhibitors should be evaluated. If a legitimate indication exists for their use, proton pump inhibitor discontinuation is not necessary. BEST PRACTICE ADVICE 14: Individuals with a history of C difficile infection should be specifically counseled to avoid unnecessary antibiotic therapy.
