Secondary Prevention of Clostridioides Difficile Using Vancomycin

Inclusion Criteria 1. Inpatient or outpatient adults (≥18 years old) treated at the participating institutions. 2. 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. 3. 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). 4. 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. Clinical Exclusion Criteria 1. ≥72 hours of off-study vancomycin prophylaxis for the current episode of antibiotic re-exposure. 2. ≤1 day elapsed since discontinuation of CDI treatment 3. Treatment of the qualifying episode of CDI with metronidazole monotherapy or intravenous immunoglobulins. 4. Planned treatment with or treatment of the qualifying episode of CDI with fecal microbiota transplantation (FMT), bezlotoxumab, VOWST, REBYOTA, or another microbiome agent. 5. Inability to take medications orally. 6. Ileostomy, colostomy, or total colectomy with ileorectal anastomosis. 7. Severe intolerance or allergy to oral vancomycin. 8. Lack of achievement of clinical cure during the treatment of the qualifying CDI episode 9. 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). 10. 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. 11. Patients admitted to a palliative care ward or who are anticipated to die within 8 weeks of enrollment from another illness. 12. The qualifying antibiotic is non-systemic (i.e., topical) or is not considered a significant risk factor for CDI including: single-dose antibiotics, as well as macrolides, nitrofurantoin, intravenous vancomycin, metronidazole, tetracyclines, and oral fosfomycin. If two or more systemic antibiotics are given (i.e., ceftriaxone and azithromycin), as long as at least one of the systemic antibiotics does not meet exclusion criteria, then the patient will still be eligible. 13. Concomitant receipt of rifaximin (e.g., for hepatic encephalopathy). 14. Receipt of ≥2 courses of vancomycin prophylaxis since the qualifying episode of CDI or \<2 weeks since the last course of vancomycin prophylaxis. 15. Treating team declined participation. Administrative Exclusion Criteria 1. Prior enrollment in this trial. 2. Inability to consent and without a healthcare proxy. 3. Lack of health insurance. 4. Anticipated transfer to a site not involved in this trial or to a palliative care ward. 5. Patient declared anticipated inability to participate in study follow-up or lack of means for contact in the outpatient setting.