Indirect evidence from network meta-analyses of randomized controlled trials (RCTs) suggest that a pulse and taper (P-T) of vancomycin may be non-inferior to 10-days of fidaxomicin for the prevention of recurrent Clostridioides difficile infections (rCDI). The aim of this trial is:
1\) For first episodes and first recurrences of CDI, to test whether a vancomycin P-T is non-inferior to 10-days of fidaxomicin for the prevention of rCDI at 56 days
Inpatient or outpatient adults (≥18 years old) treated at the participating institutions.
First episode or first recurrence of CDI (i.e., second episode within 120 days) defined by a positive C. difficile assay (including PCR toxin gene detection, toxin enzyme immunoassay, and/or cell cytotoxicity neutralization assay) and the presence of either ≥3 unformed stools in <24 hours with a duration >24 hours, endoscopic/histologic evidence of pseudomembranous colitis, or ileus. For eligibility, CDI will be considered a first recurrence if the patient experiences 2 episodes within a 120-day timeframe; those with a first ever episode, or 2 episodes separated by more than 120 days, will be categorized as a first-episode.
Treatment with CDI-active antibiotics that will be continued throughout the trial (i.e., rifaximin for hepatic encephalopathy).
Planned or current treatment of the present episode of CDI with FMT, intravenous immunoglobulins, or other microbiome therapies (i.e., VOWST or REBYOTA).
Inability to take medications orally.
Ileostomy, colostomy, or total colectomy with ileorectal anastomosis.