We recommend against probiotics for the prevention of C. difficile infection (CDI) in patients being treated with antibiotics.

We recommend against probiotics for the prevention of CDI recurrence.

CDI testing algorithms should include both a highly sensitive and a highly specific testing modality to help distinguish colonization from active infection.

We recommend that oral vancomycin 125 mg 4 times daily for 10 d be used to treat an initial episode of nonsevere CDI.

We recommend that oral fidaxomicin 200 mg twice daily for 10 d be used for an initial episode of non-severe CDI.

Oral metronidazole 500 mg 3 times daily for 10 d may be considered for treatment of an initial non-severe CDI in low-risk patients.

As initial therapy for severe CDI, we recommend vancomycin 125 mg 4 times a day for 10 d.

As initial therapy for severe CDI, we recommend fidaxomicin 200 mg twice daily or 10 d.

Patients with fulminant CDI should receive medical therapy that includes adequate volume resuscitation and treatment with 500 mg of oral vancomycin every 6 hr daily for the first 48–72 hr. Combination therapy with parenteral metronidazole 500 mg every 8 hr can be considered.

For patients with an ileus, the addition of vancomycin enemas (500 mg every 6 hr) may be beneficial.

We suggest fecal microbiota transplantation (FMT) be considered for patients with severe and fulminant CDI refractory to antibiotic therapy, particularly, when patients are deemed poor surgical candidates.

We suggest tapering/pulsed dose vancomycin for patients experiencing a first recurrence after an initial course of fidaxomicin, vancomycin, or metronidazole.

We recommend fidaxomicin for patients experiencing a first recurrence after an initial course of vancomycin or metronidazole.

We recommend patients experiencing their second or further recurrence of CDI be treated with FMT to prevent further recurrences.

We recommend FMT be delivered through colonoscopy or capsules for treatment of rCDI; we suggest delivery by enema if other methods are unavailable.

We suggest repeat FMT for patients experiencing a recurrence of CDI within 8 wk of an initial FMT.

For patients with rCDI who are not candidates for FMT, who relapsed after FMT, or who require ongoing or frequent courses of antibiotics, suppressive oral vancomycin may be used to prevent further recurrences.

Oral vancomycin prophylaxis may be considered during subsequent systemic antibiotic use in patients with a history of CDI who are at high risk of recurrence to prevent further recurrence.

We suggest bezlotoxumab be considered for prevention of CDI recurrence in patients who are at high risk of recurrence.

We suggest against discontinuation of antisecretory therapy in patients with CDI, provided there is an appropriate indication for their use.

We recommend C. difficile testing in patients with inflammatory bowel disease (IBD) presenting with an acute flare associated with diarrhea.

We suggest vancomycin 125 mg p.o. 4 times a day for a minimum of 14 d in patients with IBD and CDI.

FMT should be considered for recurrent CDI in patients with IBD.