Gut Microbiota Transplant Pro Position Christina Surawicz, MD, MACG Professor of Medicine University of Washington Seattle WA
My Focus Recurrent Clostridium difficile infection No uniformly successful therapy One recurrence 10-20% 18 % in Europe in 2008 (Bauer et al Lancet 2011; 337: 63-73) After one recurrence, rates rise to 40-65% (McFarland et al, Am J Gastroenterol 2002;97:1769-1775)
History of Fecal Bacteriotherapy Dr. Faming Zhang, MD, PhD, Nanjing Medical University, Nanjing China Should we standardize the 1700-year old fecal microbiota transplant? Letter to the editor: Am J Gastroenterol 2012, in press
Dong jin Dynasty China, 4 th Century Ge Hong, traditional Chinese medicine doctor, used human fecal suspension given orally to treat food poisoning and severe diarrhea
Results Results were a Medical Miracle Brought patients back from severe illness Reported in 1 st Chinese handbook of emergency medicine
Ming Dynasty 16 th Century Li Shizhen used, with success, Fermented or fresh or dried or infant feces Treatment of GI illness, including diarrhea Called yellow soup for esthetic reasons Reported in Compendium of Materia Medica
Europe 17 th Century Veterinary medicine transfaunation Reported by the Italian anatomist Fabricis Aquapendente
US: 2 Surgical Series Fecal enemas to treat pseudomembranous enterocolitis - 4 patients with success (Eisman et al, Surgery 1958; 44:854-9) Another case series Severe PMC fecal enemas successful (Bowden et al, Amer Surgeon 1981; 47:178-83)
Successful Treatment of RCDI Fecal enemas 1 case RCDI (Schwan et al Lancet 1983; 2:845) Rectal instillates of microbes, a mixture of 10 aerobic and anaerobic species in 6 pts with RCDI (Tvede and Rask Madsen Lancet 1989 1:1156-60)
Quotes from myself Year 1998 Fecal enemas to treat RCDI is just a measure of how desperate patients and their doctors are. Year 2012 FMT is my last resort in therapy, when all else fails, but has been very effective in curing RCDI.
Why the Change? No other effective therapy Vancomycin long term? Many patients young Results speak for themselves
RCDI - Fecal Microbiota Transplant Case report healthy spouse donor stool to right colon via colonoscopy (Persky and Brandt, Am J Gastroenterol 2000; 95:3283-5) Stool Per NG tube 16/18 cured (Aas et al, Clin Inf Dis 2003; 36:58--85) 11/15 cured (Macconachie et al, QJM 2009; 102: 781-4) Enemas given at home (Silverman et al Clin Gastro Hep 2010; 8: 471-3)
Results of FMT for Recurrent CDI- Systematic Review 317 patients, 26 papers, stool delivered by all routes 92% success 89% after one treatment 5% after retreatment Lowest response rate with NGT-76% (Gough et al, Clin Inf Dis, 2011; 53:994-1002)
My Experience- 34 patients 1 recurred with antibiotic Treated with probiotics, resolved 2 re-transplanted with different donor with success 2 with Crohn s C. difficile gone but still with symptoms (active Crohn s) 2 with enemas alone EVERY PATIENT S C DIFFICILE HAS BEEN ERADICATED
Long Term Follow Up of Colonoscopic FMT for RCDI Larry Brandt Bronx, NY Colleen Kelly Providence, RI Mark Mellow Oklahoma City, OK Neil Stollman Berkley, CA Chris Surawicz Seattle, WA (Am J Gastro, March 27, 2012)
Results 77 patients - 56 women Duration - 11 months average Age 22-88 (65 mean) Resolution within 6 days commonly 91% immediate cure, 98% secondary cure Of 7 failures 2 retransplanted 4 retreated 53% would have it as a 1 st treatment if recurred
Patient Comments 49 year old woman 2007 I will always do fecal transplant. I could not leave my house. Flying to Seattle almost killed me I had not eaten to prevent accidents. The fecal transplant saved my life immediately and permanently.
Patient Comments Mother of 18 year old woman last month My daughter thanks God for you every day we are heading out for a week long camping trip, first this year, she now feels she can leave the house without C. difficile following her.
Many Unanswered Question Does it Really Work? NIH funded study Randomized controlled trial begins October 15, 2012 Drs. Colleen Kelly (Brown University, RI) Lawrence Brandt (A Einstein University, NYC)
Unanswered Questions If it Works 1. Is it safe? 2. Donor Screening criteria and who pays 3. Best route, how much Frozen OK? Donor pool? 4. Are there other alternatives?
Other Uses? Severe CDI anecdotal cases IBD IBS Obesity Autism Multiple Sclerosis IBD + CDI All speculative
Why is it Important? It tells us how important the microbiome is
Thank you