Transcript Fecal Microbiota Transplant 9.14.2013

Fecal Microbiota
Transplantation (FMT)
Spencer A. Wilson, MD
Northside Gastroenterology
September 14, 2013
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
Intestinal Microbiota
 Includes bacteria, archea (single-celled
prokaryotes), viruses, fungi and
parasites
 > 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 2005:308;1635-8
Intestinal Microbiota:
Role in Health and Disease
De Vos, WM. SelfCare 2012;3(S1):1-68
Intestinal Microbiota:
Alterations During Human Life Cycle
Ottman, N. Front Cell Infect Microbiol. 2012;2:104
Intestinal Microbiota:
Environmental Influence and Immune Response
Microbiota and Host Physiology
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 > 65 y/o
 ~ 3.2 billion dollars excess
cost of care
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
Recurrent CDI
 15-20% of patients
 Relapse
 Re-infection
 Post-CDI irritable bowel syndrome
 2nd recurrence: 40%; 3rd recurrence 60%
 Rx failure before 2003 < 10%; after 2003 ~ 20%
 Relapses can continue for years
 No universal Rx algorithm
Why Do We Get Recurrent CDI ?
 Impaired host-response
 Altered intestinal microbiome
 “Dysbiosis” = decreased microbiota
diversity
Host Immune Response to C.
difficile Infection
 IgG anti-toxin A protects against diarrhea and colitis
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 2008:197;435-8
ACG Rx Guidelines 2013
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
Recurrent CDI:
Rationale for FMT
 Avoid prolonged, repeated courses
of antibiotics
 Re-establish normal diversity of the
intestinal microbiome, thus restoring
“colonization resistance”
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
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, O&P, 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
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
Protocol for FMT in Recurrent CDI
 Stool Transplant
 Donor stool  suspension with nonbacteriostatic 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
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;
FMT in Recurrent CDI:
1st RCT of FMT vs Oral Vanco
Van Nood N et. al. NEJM 2013
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
Follow-up Survey
 77 patients > 3 months after FMT
 Duration of illness: 11 months
 Symptomatic response after FMT
 < 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
FMT for Recurrent CDI
 Drawbacks
 Aesthetically unpleasing
 No remibursement
 Cautions
 Potential transmission of pathogens
 Pros
 Re-establishes diversity of intestinal
microbiota
 Inexpensive
 Efficacy > 90%
 Rapidly effective (within hours-days)
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
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
Questions ?