Please select the eligibility criteria that correspond to the clinical trial below.
Title: Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection
Brief Summary: There has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in North America over the past decade. Relapsing infection is a common problem in patients treated for CDI, often requiring prolonged and expensive courses of oral vancomycin with limited alternative treatment options. This study will determine if fecal microbiota transplantation, which involves administering fecal flora from a healthy stool donor to a patient with relapsing CDI, is an effective and safe treatment.


Options:
A: Inclusion criteria:

* Recurrent C. difficile infection (identified by positivity of C. difficile toxin in stools) with severe clinical picture (defined by the ESCMID Guidelines published in 2014 - Debast et al, Clin Microbiol Infect 2014)
* Possibility to undergo standard antimicrobial therapy for recurrent C. difficile infection Approval of informed consent
* Possibility to undergo protocol diagnostic and therapeutic procedures
* Stool negativity for parasites
* Stool negativity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
* Blood negativity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).

Exclusion Criteria:

* Subjects \<18 years old
* Prior colectomy
* Negativity of C. difficile toxin in stools
* Mild clinical picture of C. difficile infection
* High risk of post-colonoscopy complications
* Other main gastrointestinal diseases (es. Crohn's disease or ulcerative colitis)
* Stool positivity for parasites
* Stool positivity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
* Blood positivity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).
* Pregnancy or breastfeeding.
* Inability to follow protocol procedures
B: Inclusion Criteria for patients:

* Patients with IBS-D according to Roma 3 criteria

Exclusion Criteria for patients:

* Immunomodulating medication
* Nocturnal abdominal pain
* Constant abdominal pain
* Alarm symptoms like rectal bleeding, weight loss, nightsweats
* Symptomatic heart/vascular/lung disease
* Renal failure
* Known food allergy
* Microscopic/collagenous colitis
* non-compliant
* BMI \<18

Inclusion criteria for donors:

* healthy volunteers

Exclusion criteria for donors

* Tattoos, imprisoning or piercing last 3 months
* Any history of chronic diarrhoea, constipation, inflammatory bowel disease, irritable bowel disease, colorectal polyps or cancer, immunosuppression, morbid obesity, metabolic syndrome, atopica, or fatigue
* positive test for hepatitis B, C, HIV, treponema pallidum
* sexual high risk habits
* antibiotic treatment in the past 3 months
C: Inclusion Criteria:

1. Adult outpatients (age ≥18 and \<75) referred to one of the study centers after suffering a third (or further) documented episode CDI and
2. who have failed to maintain CDI cure after standard therapy with oral vancomycin.

   * Previous treatment with at least one course of tapered/pulse dose vancomycin as per SHEA-IDSA C difficile treatment guidelines or -Inability to taper or stop vancomycin without developing diarrhea requiring anti-infective therapy. -

Exclusion Criteria:

* Patients who are aged 75 years or greater.
* Patients who are pregnant
* Patients who are nursing
* Patients who are incarcerated
* Patients with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving their own informed consent
* Patients who are immunocompromised specifically:
* HIV infection (any CD4 count)
* AIDS-defining diagnosis or CD4\<200/mm3
* Inherited/primary immune disorders
* Immunodeficient or Immunosuppressed due to medical condition/medication:
* Current or recent (\<3 most) treatment with anti-neoplastic agent
* Current or recent (\<3 mos) treatment with any immunosuppressant medications (including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil). Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
* Patients with a history of severe (anaphylactic) food allergy
* Patients who have previously undergone FMT
* Patients who are unwilling or unable to undergo colonoscopy
* Patients with untreated, in-situ colorectal cancer
* Patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn"s disease or microscopic colitis) or irritable bowel syndrome
* Unable to comply with protocol requirements
* Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
* Patients with acute illness or fever on the day of planned FMT will be excluded (not undergo randomization or treatment with FMT) with the option of including that subject at a future date.
D: Inclusion Criteria:

* Patients with recurrent or relapsing CDI defined as EITHER(13):

  * At least three episodes of mild-to-moderate CDI and failure of a 6-8 week taper with vancomycin with or without an alternative antibiotic (e.g. rifaximin, nitazoxanide).
  * At least two episodes of severe CDI resulting in hospitalization and associated with significant morbidity.
* Willingness to accept risk of unrelated donor stool
* Willingness to be randomized to NGT vs. colonoscopic delivery.
* Able to consent for self, or parental assent/child assent as age appropriate.

Exclusion Criteria:

* Anatomic contraindication to NGT
* Delayed gastric emptying syndrome
* Known chronic aspiration
* Contraindication to colonoscopy (ASA 4 or more)
* High risk of bacterial translocation (Immunosuppression, cirrhosis etc)
* Pregnant or breastfeeding women
* Acute unrelated infection or comorbid illness exaccerbation

Answer: C