Re-exposure to systemic antibiotics (i.e., antibiotics absorbed into the bloodstream) is common after a Clostridioides difficile infection (CDI) and is the strongest risk factor for a recurrent episode. Oral vancomycin to prevent a recurrence during antibiotic re-exposure may reduce this risk but the data supporting this practice are limited. The aim of this trial is:
1\) Does oral vancomycin prophylaxis prevent CDI recurrences in patients with recent CDI (within 120 days) and who are re-exposed to systemic antibiotics?
The trial will compare oral vancomycin to placebo.
Participants will:
* Take the study drug (either vancomycin or placebo) twice daily for the duration of systemic antibiotics plus once daily for 7 days after completion of systemic antibiotics. * Attend an in-person or over the phone follow-up at day 56 * Respond to weekly electronic questionnaires
Inpatient or outpatient adults (≥18 years old) treated at the participating institutions.
An episode of CDI within the preceding 120 days, diagnosed by both 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.
Treatment of the qualifying CDI episode with vancomycin or fidaxomicin for ≥10 days, and achievement of clinical cure (≤3 unformed stool per 24 hours in ≥2 days10).
Receipt of ≤3 days of at least one oral or intravenous systemic antibiotic, for which therapy is planned for at least one additional consecutive day in duration.
≥72 hours of off-study vancomycin prophylaxis for the current episode of antibiotic re-exposure.
≤1 day elapsed since discontinuation of CDI treatment
Treatment of the qualifying episode of CDI with metronidazole monotherapy or intravenous immunoglobulins.
Planned treatment with or treatment of the qualifying episode of CDI with fecal microbiota transplantation (FMT), bezlotoxumab, VOWST, REBYOTA, or another microbiome agent.