Placebo Controlled Study of Fecal Microbiota Transplant (FMT) for a First or Second Episode of C. Difficile Infection in Adults Using a Frozen Encapsulated Inoculum

Inclusion Criteria: * Patients with two episodes of Clostridium dificile infection defined as having resolved symptoms after an initial microbiologically confirmed diagnosis of C. difficile, who have completed a course of antibiotics, and have a second positive test (toxin or PCR) obtained for a relapse of diarrhea symptoms by treating providers. Subjects with a positive "test of cure" stool sample (NOT advised by SHEA guidelines) in the absence of relapsed symptoms of CDI, or those who never improved their symptoms on the initial course of antibiotics will not be eligible. (Subjects who do not have a response to antibiotics may have other or additional diagnoses which are not likely to be helped by FMT.) * Willingness to accept risk of unrelated donor stool. * Age 18 or above. We do not believe there is a reason to have an upper age limit as long as patients can consent and can swallow large capsules. The elderly are disproportionately affected by CDI in terms of incidence, severity and affect on quality of life given limited mobility. * Able to consent for self. * Subjects are not expected to receive additional antibiotics for other indications in the next 8 weeks. * Patients on a standard chemotherapeutic regimen for solid tumors, where significant duration of neutropenia is NOT expected in the 2 weeks following FMT may be enrolled with the agreement of their oncologist. * Pt must be willing to have baseline Hepatitis B and C screening, and HIV screening (as required by the FDA for past studies). Those known to be seropositive for any of these illnesses need not be retested. These illnesses do not exclude subjects a priori, we simply wish to document initial sero-status. * Subjects who have completed a second course of antibiotics may be enrolled up to 7 days after completing their second course of antibiotics for C. difficile Exclusion Criteria: * Delayed gastric emptying syndrome * Known chronic aspiration * Swallowing dysfunction or oral-motor dyscoordination, or inability or unwillingness to swallow multiple large capsules * Pregnant women; we have previously and will continue to include postpartum and breastfeeding women. Women of child bearing potential have a urine or serum human chorionic gonadotropin test at enrollment. * Patients with an acute illness unrelated to CDI or an acute exacerbation of underlying co-morbid condition * Neutropenia (ANC \<500) currently or expected within 2 weeks of FMT. (must have count within 7 d in relevant subjects, i.e. those with recent chemotherapy) * Subjects on high dose steroids (\>40 mg daily) * Subjects on multiple/combination immunosuppressive regimens including high dose corticosteroids, calcineurin inhibitors, lymphocyte depleting biologic agents, anti-tumor necrosis factor agents. Subjects on a stable dose of a SINGLE immunosuppressive agent like steroids, rituximab, infliximab, other anti-TNF agents, with approval of the treating physician may be enrolled. These subjects may be at greatest risk of complications and hospitalization if another relapse of CDI occurs and may benefit. * Patients with decompensated cirrhosis, advanced HIV/AIDS, recent bone marrow transplant, other cause of severe immunodeficiency. * Patients with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs) * Ongoing systemic antibiotics for other infections (these people are better maintained on suppressive vancomycin and transplanted later). Subjects may have recently completed a course of antibiotics for another indication. * Advanced HIV/AIDS with cluster of differentiation 4 cells (CD4) count less than 50. * Allergy to chocolate/cocoa or gelatin, or unwillingness to ingest gelatin (in placebo capsules).