Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 years and older.
4. Admitted to UVA hospital, or seen as an outpatient, or seen at Carilion hospital.
5. Presence of diarrhea*
6. Episode of C. difficile infection, non-severe or severe uncomplicated.
7. Within 120 hours of receiving standard therapy (oral vancomycin or fidaoxmicin).
8. Must be able to provide informed consent in person or electronically, or if not able to have a LAR to provide consent, in person or remotely via virtual or electronic means.

Exclusion Criteria:

1. At enrollment, presence of any of the following:

   1. Hypotension or shock
   2. Megacolon or moderate to severe ileus
   3. Acute abdomen
   4. Admission to intensive care unit

2. Inability to tolerate oral or enteral medication

3. Presence of other known infectious etiology of diarrhea

4. COVID-19 co-infection at the time of CDI diagnosis.

5. Absolute neutrophil count <500 mcl

6. Within 100 days of hematologic or solid organ transplant

   • Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or other etiology of non-infectious diarrhea. For patients with history of IBD, allow enrollment if disease is well-controlled and stable (not in flare).

7. Enrollment in another investigational drug trial

8. Current use of alternative treatment for CDI (e.g. antibiotics other than vancomycin or fidaxomicin; IVIg; fecal transplant).

9. On probiotics and not willing to discontinue.

10. Cirrhosis or in participants with ALT > 3X normal

11. End stage renal disease, unless on dialysis(HD or PD) or creatinine clearance or estimated GFR of <30mL/min even after adequate hydration

12. Life expectancy of < 6 months.