Impact of Intestinal Colonization with Clostridioides difficile on Clinical Outcomes in Alcohol-associated Hepatitis.

Test only patients with symptoms suggestive of active CDI (≥3 unformed stools in 24 hours); testing patients with formed stool is rarely clinically indicated. Use a testing algorithm including both a highly sensitive and a highly specific modality to distinguish colonization from active infection (conditional recommendation, low quality evidence): begin with a highly sensitive test (GDH or NAAT), and if positive proceed to the more specific toxin EIA. A sensitive-test-positive/toxin-EIA-negative result means not CDI or colonization, a false-negative EIA, or toxin below detection, it requires clinical evaluation, and treatment should not be withheld when clinical suspicion is high, because no test is perfect and the diagnosis is a clinical one. Classify as severe when WBC ≥15,000 cells/mm3 or serum creatinine >1.5 mg/dL; classify as fulminant when severe criteria are met plus hypotension or shock, or ileus, or megacolon. INITIAL NONSEVERE EPISODE, ACG gives two co-equal strong recommendations, not a preference: oral vancomycin 125 mg 4 times daily for 10 days (strong recommendation, low quality) OR oral fidaxomicin 200 mg twice daily for 10 days (strong recommendation, moderate quality); oral metronidazole 500 mg 3 times daily for 10 days may be considered for an initial nonsevere episode in LOW-RISK patients (strong recommendation, moderate quality), ACG explicitly retains metronidazole as an appropriate alternative for lower-risk patients (younger outpatients with minimal comorbidities, cost-sensitive environments). SEVERE CDI, vancomycin 125 mg 4 times daily for 10 days (strong, low quality) or fidaxomicin 200 mg twice daily for 10 days (conditional, very low quality). FULMINANT CDI, adequate volume resuscitation plus oral vancomycin 500 mg every 6 hours for the first 48-72 hours (strong recommendation, very low quality); combination therapy with parenteral metronidazole 500 mg every 8 hours can be considered (conditional, very low); for patients with ileus, adding vancomycin enemas 500 mg every 6 hours may be beneficial (conditional, very low); FMT is suggested for severe and fulminant CDI refractory to antibiotic therapy, particularly when patients are poor surgical candidates (strong recommendation, low quality). Surgical options (total colectomy with end ileostomy vs diverting loop ileostomy with colonic lavage and intraluminal vancomycin) depend on clinical circumstances and surgeon judgment. FIRST RECURRENCE, tapering/pulsed-dose vancomycin after an initial course of fidaxomicin, vancomycin, or metronidazole (strong recommendation, very low quality), or fidaxomicin after an initial course of vancomycin or metronidazole (strong recommendation, moderate quality). SECOND OR FURTHER RECURRENCE, treat with FMT to prevent further recurrences (strong recommendation, moderate quality), delivered by colonoscopy or capsules (strong, moderate), with enema suggested only if other methods are unavailable (conditional, low); repeat FMT is suggested for recurrence within 8 weeks of an initial FMT (conditional, very low). Suppressive oral vancomycin may be used to prevent further recurrences in rCDI patients who are not FMT candidates, who relapsed after FMT, or who require ongoing/frequent antibiotics (conditional, very low). Bezlotoxumab is suggested for prevention of CDI recurrence in patients at HIGH RISK OF RECURRENCE (conditional recommendation, moderate quality), ACG ties it to recurrence risk, not to a specific recurrence number. Antisecretory therapy should not be discontinued in patients with CDI provided there is an appropriate indication for its use (strong, very low). IBD, test for C. difficile in patients with IBD presenting with an acute flare associated with diarrhea (strong, low); vancomycin 125 mg 4 times daily for a MINIMUM OF 14 DAYS in patients with IBD and CDI (strong, very low); FMT should be considered for recurrent CDI in IBD (strong, very low). Vancomycin is recommended for pregnant, peripartum, and breastfeeding patients; vancomycin or fidaxomicin first line if immunocompromised. Do NOT test for cure: routine testing in asymptomatic patients after treatment is not recommended, because persistent shedding occurs in 56% of patients who had resolution of diarrhea as long as 4 weeks after completing treatment.