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

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Presentation on theme: "Fecal Microbiota Transplantation (FMT) Spencer A. Wilson, MD Northside Gastroenterology September 14, 2013 Spencer A. Wilson, MD Northside Gastroenterology."— Presentation transcript:

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

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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  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  > 50 bacterial phyla described  Majority anaerobic  Constitute 60% of dry weight of feces  Bacteroides, Firmicutes, Actinobacteria, Proteobacteria  bacterial cells  10 times greater than number of human cells in our body  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  bacterial cells  10 times greater than number of human cells in our body Eckburg, PB et al. Science 2005:308;1635-8

5 Intestinal Microbiota: Role in Health and Disease De Vos, WM. SelfCare 2012;3(S1):1-68

6 Intestinal Microbiota: Alterations During Human Life Cycle Ottman, N. Front Cell Infect Microbiol. 2012;2:104

7 Intestinal Microbiota : Environmental 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 > 65 y/o  ~ 3.2 billion dollars excess cost of care  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

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  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  2 nd recurrence: 40%; 3 rd recurrence 60%  Rx failure before 2003 < 10%; after 2003 ~ 20%  Relapses can continue for years  No universal Rx algorithm  15-20% of patients  Relapse  Re-infection  Post-CDI irritable bowel syndrome  2 nd recurrence: 40%; 3 rd recurrence 60%  Rx failure before 2003 < 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  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 2008:197;435-8  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

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  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”  Avoid prolonged, repeated courses of antibiotics  Re-establish normal diversity of the intestinal microbiome, thus restoring “colonization resistance”

18 Early History of FMT  4 th Century:  Oral human fecal suspension (“yellow soup”) for severe diarrheal illnesses  17 th 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  4 th Century:  Oral human fecal suspension (“yellow soup”) for severe diarrheal illnesses  17 th 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  1 st 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  Choose donor  Spouse/partner  1 st 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

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  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  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): ;

23 FMT in Recurrent CDI: 1 st RCT of FMT vs Oral Vanco Van Nood N et. al. NEJM 2013

24 FMT in Recurrent CDI: 1 st RCT of FMT vs Oral Vanco Van Nood N et. al. NEJM 2013 *** Trial stopped early as deemed unethical to continue

25 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  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

26 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)  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)

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