Clinical Infectious Diseases Advance Access published December 7, 2012

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Clinical Infectious Diseases Advance Access published December 7, 2012 1 Physician Attitudes Towards the Use of Fecal Transplantation for Recurrent Clostridium Difficile Infection in a Large Metropolitan City Zhi-Dong Jiang 1,*, Ly Hoang 2, Todd Lasco 3, Kevin Garey 3,4, Herbert L. DuPont 1,2,3,4,5 1 University of Texas School of Public Health, Houston, TX 2 University of Texas Medical School, Houston, TX 3 ST Luke s Episcopal Hospital, Houston, TX 4 University of Houston, Houston, TX 5 Baylor College of Medicine, Houston, TX * Corresponding Author: Zhi-Dong Jiang, MD, PhD, 1200 Herman Pressler Rm 741, Houston, TX 77030, Ph: 7135009371, Email: zhi-dong.jiang@uth.tmc.edu The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e mail: journals.permissions@oup.com

2 In the United States and Canada there has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in the last decade 1. It is now estimated that between 500,000 and 700,000 cases of CDI occur in U.S. hospital annually with an estimated hospital excess cost of care of about 3.2 billion dollars 2,3. With the increase in risk of developing CDI, high rates of disease recurrence is being seen without the availability of adequate treatment 5,6. It is now accepted that disruption of the normal balance of colonic microbiota secondary to antibiotic use facilitates the development of CDI and improvements in the quality and quantity of flora is associated with recovery of infection and disease recurrence. Studies have shown that patients with recurrent CDI have decreased anaerobic bacteroidetes and firmicutes in their stool compared to patients recovering from single episodes of CDI 14. Numerous case reports and retrospective case series have demonstrated benefit of fecal transplantation (FT) in patients with severe or recurrent CDI with cure rates over 90% 7-12. FT involves administration of a suspension of feces obtained from a healthy individual into the colon of a patient with recurrent CDI to promote normalization of flora and inhibition of the infecting C. difficile 8. Probiotics have been used widely for patients with CDI in efforts to repair the disruption of microbiota leading to prevention and control of CDI 15, however the available probiotics have been shown to have a limited effect failing to reach the efficacy of fecal transplantation from a healthy volunteer. Despite growing evidence supporting safety 13 and efficacy 7-12 of FT in CDI this form of treatment is not widely available. The aim of the study was to determine physician attitudes

3 towards the use of FT in the city of Houston to see if there was sufficient local interest to support development of a treatment center. Using a questionnaire mailed to city wide gastroenterologists and infectious diseases specialists listed in a roster maintained by the Harris County Medical Association, we attempted to assess physicians willingness to provide patients with recurrent or refractory CDI to a local center for FT therapy. Two hundred sixty-four surveys were sent to 187 gastroenterologists (GI) and to 77 infectious diseases (ID) specialists in Harris County (Houston), Texas. Rate of response for the survey was 34% (89 completed/returned) overall. Fifty-five (29%) of the GI doctors and 32 (42%) of the ID specialists completed a survey (Table). A majority of the responding physicians from the two medical groups were supportive of the creation of a local FT center (35/55 = 64% for GI physicians and 22/32 = 69% for ID physicians, p=0.628). A high percent of responding gastroenterologists (49/55, 89%) and infectious diseases specialists (26/32, 81%) indicated that they would refer patients to a newly developed local FT center. We are encouraged to pursue the development of a FT center in Houston and would like to encourage other academic units outside our city to develop FT programs to improve therapy of local patients and to engage in studies of pathophysiology of successful CDI management. Improvements in FT efficiency is likely to be seen by using frozen fecal aliquots or lyophilized fecal samples from a single donor for multiple patients. Mechanisms of FT effects should follow studies to characterize the colonic microbiome in patients with CDI and CDI recurrence by metagenomic methods. We all should be working toward a more acceptable and replicable form

4 of non-fecal therapy of refractory cases of CDI using selective flora, cocktails of probiotics or manufactured bacterial flora metabolic products. The authors have no reported conflicts of interest.

5 Table Need Fecal Transplantation Center Wide Specialist Refer Patients to Fecal Transplantation Center City Wide Yes (%) No (%) Neutral (%) Yes (%) No (%) Gastroenterologist (N=55) 35 (64) 4 (7) 16 (29) 49 (89) 6 (11) Infectious Diseases Specialist (N=32) 22 (69) 5 (16) 5 (16) 26 (81) 6 (19) Downloaded from http://cid.oxfordjournals.org/ at Pennsylvania State University on March 5, 2016

6 REFERENCES 1. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerging infectious diseases 2006;12:409-15. 2. Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2002;34:346-53. 3. O'Brien JA, Lahue BJ, Caro JJ, Davidson DM. The emerging infectious challenge of clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America 2007;28:1219-27. 4. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America 2010;31:431-55. 5. McFarland LV. Alternative treatments for Clostridium difficile disease: what really works? Journal of medical microbiology 2005;54:101-11. 6. McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America 1999;20:43-50.

7 7. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989;1:1156-60. 8. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Journal of clinical gastroenterology 2010;44:354-60. 9. Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. Journal of clinical gastroenterology 2010;44:567-70. 10. Yoon SS, Brandt LJ. Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients. Journal of clinical gastroenterology 2010;44:562-6. 11. Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2010;8:471-3. 12. You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Annals of internal medicine 2008;148:632-3. 13. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2011;53:994-1002. 14. Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. The Journal of infectious diseases 2008;197:435-8.

8 15. Gorbach SL. Probiotics and gastrointestinal health. The American journal of gastroenterology 2000;95:S2-4. 16. McFarland LV, Surawicz CM, Greenberg RN, et al. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. The American journal of gastroenterology 1995;90:439-48. 17. Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2000;31:1012-7. 18. Wullt M, Hagslatt ML, Odenholt I. Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scandinavian journal of infectious diseases 2003;35:365-7. 19. Lawrence SJ, Korzenik JR, Mundy LM. Probiotics for recurrent Clostridium difficile disease. Journal of medical microbiology 2005;54:905-6.