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Fecal Microbiota Transplantation (FMT)

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Title: Fecal Microbiota Transplantation (FMT)


1
Fecal Microbiota Transplantation (FMT)
  • Spencer A. Wilson, MD
  • Northside Gastroenterology
  • September 14, 2013

2
(No Transcript)
3
Overview
  • Intestinal microbiome and host physiology
  • Dysbiosis of the microbiome and C. difficile
    infection (CDI)
  • Standard Rx of CDI
  • FMT for restitution of colonization resistance
  • Rx of recurrent/refractory CDI
  • The future of FMT

4
Intestinal Microbiota
  • Includes bacteria, archea (single-celled
    prokaryotes), viruses, fungi and parasites
  • gt 50 bacterial phyla described
  • Majority anaerobic
  • Constitute 60 of dry weight of feces
  • Bacteroides, Firmicutes, Actinobacteria,
    Proteobacteria
  • 1014 bacterial cells ? 10 times greater than
    number of human cells in our body

Eckburg, PB et al. Science 20053081635-8
5
Intestinal MicrobiotaRole in Health and Disease
De Vos, WM. SelfCare 20123(S1)1-68
6
Intestinal MicrobiotaAlterations During Human
Life Cycle
Ottman, N. Front Cell Infect Microbiol. 20122104
7
Intestinal MicrobiotaEnvironmental Influence
and Immune Response
8
Microbiota and Host Physiology
9
C. difficile Infection (CDI)
  • 1996 2009 in U.S., rates of CDI doubled
  • 3 million cases per year
  • Unadjusted fatality rate
  • 1.2 (2000) ? 2.3 (2004)
  • Majority gt 65 y/o
  • 3.2 billion dollars excess cost of care

10
C. difficile Manifestations
  • Carrier state
  • C. difficile - associated diarrhea (CDAD)
  • C. difficile colitis
  • Pseudomembranous colitis
  • Fulminant Colitis / Toxic megacolon
  • Atypical (e.g., sepsis, ascites)
  • Recurrent disease

11
Recurrent CDI
  • 15-20 of patients
  • Relapse
  • Re-infection
  • Post-CDI irritable bowel syndrome
  • 2nd recurrence 40 3rd recurrence 60
  • Rx failure before 2003 lt 10 after 2003 20
  • Relapses can continue for years
  • No universal Rx algorithm

12
Why Do We Get Recurrent CDI ?
  • Impaired host-response
  • Altered intestinal microbiome
  • Dysbiosis decreased microbiota diversity

13
Host Immune Response to C. difficile Infection
  • IgG anti-toxin A protects against diarrhea and
    colitis

14
Decreased Diversity of Fecal Microbiome in
Recurrent CDI
  • Decreased phylogenic richness in recurrent CDI
  • Bacteroidetes reduced in recurrent but not single
    episode CDI

  • Chang JY, et al. J
    Infect Dis 2008197435-8

15
ACG Rx Guidelines 2013
16
Fecal Microbiota Transplantation (FMT)
  • Definition Instillation of stool from a healthy
    person into a sick person to cure a certain
    disease
  • Rationale A perturbed imbalance in our
    intestinal microbiota (dysbiosis) is associated
    with or causes disease and can be corrected with
    re-introduction of donor feces

Brandt LJ ACG Meeting Oct. 2012
17
Recurrent CDI Rationale for FMT
  • Avoid prolonged, repeated courses of antibiotics
  • Re-establish normal diversity of the intestinal
    microbiome, thus restoring colonization
    resistance

18
Early History of FMT
  • 4th Century
  • Oral human fecal suspension (yellow soup) for
    severe diarrheal illnesses
  • 17th Century Veterinary medicine
  • Fecal transfer for horses with diarrhea
  • 1958 FMT enema
  • Eismann, et al. 4 patients with pseudomembranous
    colitis
  • Dramatic response within 48 hours

19
Protocol for FMT in Recurrent CDI
  • Choose donor
  • Spouse/partner
  • 1st degree relative
  • Household contact
  • Universal donor
  • Donor exclusions
  • Antibiotic use within 3 months
  • Diarrhea, constipation, IBS, IBD, colorectal CA,
    immunocompromised, anti-neoplastic drugs,
    obesity, metabolic syndrome, atopy, high-risk
    behaviors
  • Donor testing
  • Stool culture, listeria, OP, C. diff, H.
    pylori Ag, Giardia Ag, cryptosporium Ag,
    acid-fast stain (cyclospora, isospora), Rotavirus
  • Blood Hep A, Hep B, Hep C, syphilis, HIV

Brandt LJ ACG Meeting Oct. 2012
20
Protocol for FMT in Recurrent CDI
  • Recipient
  • D/C antibiotics 2-3 days prior to procedure
  • Large volume bowel prep evening before FMT
  • Loperamide before procedure
  • Donor
  • Gentle laxative (e.g. MOM) evening before FMT
  • Freshly passed stool is used within 6-8 hours
  • Stool need not be refrigerated

Brandt LJ ACG Meeting Oct. 2012
21
Protocol for FMT in Recurrent CDI
  • Stool Transplant
  • Donor stool ? suspension with non-bacteriostatic
    saline
  • Filtered through gauze into canister
  • Use of hood (level 2 biohazard)
  • 60 cc catheter tip syringe connected to suction
    tubing
  • Volume of 300 mL instilled into ileum and/or
    ascending colon
  • Patient to hold stool for 4-6 hours

Brandt LJ ACG Meeting Oct. 2012
22
Current History of FMT in Recurrent C.
difficile infection
Kleger, A Schnell, J Essig, A Wagner, M
Bommer, M Seufferlein, T Härter, G Fecal
Transplant in Refractory Clostridium difficile
Colitis Dtsch Arztebl Int 2013 110(7) 108-15
23
FMT in Recurrent CDI 1st RCT of FMT vs Oral
Vanco
Van Nood N et. al. NEJM 2013
24
FMT in Recurrent CDI 1st RCT of FMT vs Oral
Vanco
Trial stopped early as deemed unethical to
continue
Van Nood N et. al. NEJM 2013
25
Follow-up Survey
  • 77 patients gt 3 months after FMT
  • Duration of illness 11 months
  • Symptomatic response after FMT
  • lt 3 days in 74
  • Primary cure rate 91
  • Secondary cure rate 98.7
  • 97 of patients would have another FMT for
    recurrent CDI
  • 58 would chose FMT as their prefered Rx

Brandt LJ, et al. Am J Gastroenterol 2012
26
FMT for Recurrent CDI
  • Drawbacks
  • Aesthetically unpleasing
  • No remibursement
  • Cautions
  • Potential transmission of pathogens
  • Pros
  • Re-establishes diversity of intestinal microbiota
  • Inexpensive
  • Efficacy gt 90
  • Rapidly effective (within hours-days)

27
Indications for FMT for CDI
  • For recurrent, refractory dz YES
  • For severe dz arguably yes
  • As first-line therapy arguably yes
  • For post-C. difficile IBS - possibly

28
Future Direction of FMT
  • Universal donor
  • Processed and frozen until use
  • RePOOPulate
  • Artificial stool synthetic alternative
  • Indications
  • Severe, complicated CDI ? 1st occurrence
  • Other GI IBD, IBS, constipation
  • Non-GI DM, obesity, Parkinson, MS, ITP, Autism?
  • Route of administration
  • LGI transplant better than UGI ?
  • Safety

29
Questions ?
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