Secondary Prevention of Clostridioides Difficile Using Vancomycin

Inclusion Criteria: * Inpatient or outpatient adults (≥18 years old) treated at the participating institutions. * An episode of CDI within the preceding 120 days (rationale in 2.4), diagnosed by both a positive C. difficile assay (including PCR toxin gene detection47, toxin enzyme immunoassay, and/or cell cytotoxicity neutralization assay29) and the presence of either ≥3 unformed stools in \<24 hours with a duration \>24 hours, endoscopic/histologic evidence of pseudomembranous colitis, or ileus29. * Treatment of the qualifying CDI episode with vancomycin or fidaxomicin for ≥10 days, clinical cure (≤3 unformed stool per 24 hours in ≥2 days10) by the conclusion of therapy, and ≥1 day has elapsed since cessation of CDI treatment. * Receipt of ≤3 days of at least one oral or intravenous systemic antibiotic for the treatment of an intercurrent confirmed or suspected bacterial infection, for which therapy is planned for at least one additional consecutive day in duration. Exclusion Criteria: * 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, or REBYOTA. * Inability to take medications orally or crushed by nasogastric tube. * Prior total colectomy. * Severe intolerance or allergy to oral vancomycin. * Lack of achievement of clinical cure during the treatment of the qualifying CDI episode * Ongoing or \<1 day since receiving CDI treatment or ongoing or \<1 days since receipt of CDI-active antibiotics, including oral vancomycin, oral or intravenous metronidazole, or fidaxomicin. * The qualifying antibiotic is solely for prophylaxis (e.g., once daily trimethoprim sulfamethoxazole) or the patient is anticipated to require systemic antibiotics for \>4 weeks (e.g., lifelong suppressive therapy or for the treatment of left-sided endocarditis or a deep-seated abscess). * Patients on ongoing systemic antibiotics since the completion of treatment for the qualifying episode of CDI that have not been interrupted by at least one day. * Patients admitted to a palliative care ward or is anticipated to die within 3 months of enrollment from another illness. * The qualifying antibiotic is non-systemic or is not considered a significant risk factor for CDI including: topical antibiotics, azithromycin, clarithromycin, nitrofurantoin, intravenous vancomycin, minocycline, tetracycline, doxycycline, and oral fosfomycin. * Prior enrollment in this trial. * Inability to consent without a healthcare proxy. * Lack of health insurance. * Anticipated transfer to a site not involved in this trial or to a palliative care ward. * Patient declared anticipated inability to participate in study follow-up or lack of means for contact in the outpatient setting.