R3 민준기 Pf. 이창균

Introduction 1978 – Clostridium difficile major cause of diarrhea – Pseudomembranous colitis associated with the use of antimicrobial agents 1996 ~ 2003 – US National Hospital Discharge Survey statistics – C. difficile infection(CDI) prevalence rate 0.61 / 1, – US acute care facilities – CDI prevalence rate of 13.1 / 1,000

Recurrent CDI Difficult and increasingly common challenges associated with CDI Complicates management of IBD – additional independent risk factor for CDI Risk factors for recurrence – Older age – antibiotic use – renal insufficiency, immune deficiency – antacid medications

Fecal microbiota transplantation(FMT) = Fecal bacteriotherapy Fastest reconstitution of a normal composition of colon microbial communities. Prompt and sustained engraftment of donor fecal bacteria in a patient with recurrent CDI

Procedure is rarely performed!! Lack of wider practice of FMT (Practical barrier) – Lack of reimbursement for donor screening – Difficulty in material preparation – Aesthetic concerns – Pharmaceutical industry has shown little interest Large part due to the wide availability of donor material complex composition

To overcome some of the associated challenges Patient-identified individual donors  rigorously screened “ universal ” volunteer donors Fresh donor fecal materials  a more standardized laboratory protocol done using frozen fecal extracts

Method

Patients 43 patients who received FMT for recurrent CDI at the University of Minnesota Fairview Medical Center Inclusion criteria for FMT – history of symptomatic, toxin-positive, infection by C. difficile – at least two documented subsequent recurrences despite use of standard antibiotic therapy. – At least one failed antibiotic regimen a minimum of a 6-week course of tapered or pulsed vancomycin dosage at least a 1-month vancomycin course followed by a minimum of 2-week rifaximin

Donor identification and screening Patient-identified individual donors – Mothers (n=2) – Daughter (n=1) – Sons (n=3) – Wife (n=1) – Husband (n=1) – Friends (n=2) – Donors underwent serologic testing for HIV and Hepatitis B and C Stool testing C. difficile toxin B examination for ova and parasites Giardia and Cryptosporidium antigens. Exclusion Criteria gastrointestinal comorbidities use of antibiotics within 3 months metabolic syndrome Autoimmunity allergic diseases

Donor identification and screening volunteer donors Advantages of this change – removing the burden of donor identification from the patient – improving the efficiency and costs related to donor screening – more consistent supply of donor fecal microbiota – Ability to impose extensive and stringent exclusion criteria on donor selection

Donor material preparation

Material obtained from volunteer donors Blendered  slurry  sieves(0.25mm)  centrifuges(6000G) for 15min  resuspended – administered immediately – amended with glycerol  frozen (-80 ℃ ) for 1- 8wks thawing 2-4hrs before procedure Fecal material extract – Nearly orderless – Reduced viscosity & color & texture – effortless loading without risk of clotting

Follow up Formally followed in clinic 1 – 2 months after the procedure Clearance of CDI – resolution of diarrhea – negative stool testing for C. difficile at 2 months following FMT

Statistical analysis Non-categorical data – unpaired Student’s t -test Categorical data – Fisher’s exact test

Results

Demographics CD 6 UC 4 lymphocytic colitis 4

Response to treatment

Conclusion

Discussion(Limitations ) It was not a rigorous clinical trial designed to test efficacy of a particular FMT methodology vs. another – Can not conclude from this experience alone that the fresh and frozen preparations are equivalent.