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Clin Colon Rectal Surg 2020; 33(02): 092-097
DOI: 10.1055/s-0040-1701233
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection

Yao-Wen Cheng
1   Department of Gastroenterology, University of California San Francisco, San Francisco, California
,
Monika Fischer
2   Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
› Author Affiliations
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Publication History

Publication Date:
25 February 2020 (online)

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Abstract

Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as “Clostridioides difficile”) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.

Keywords

Clostridium difficile - colitis - toxic megacolon - fecal microbiota transplantation - colonoscopy - colectomy
 

  • References

  • 1 Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation?. Am J Gastroenterol 2012; 107 (11) 1755 , author reply 1755–1756
    PubMedGoogle Scholar
  • 2 Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prévot 1938. Anaerobe 2016; 40: 95-99
    CrossrefPubMedGoogle Scholar
  • 3 Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol 2016; 13 (09) 508-516
    CrossrefPubMedGoogle Scholar
  • 4 McFarland LV, Surawicz CM, Greenberg RN. , et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 271 (24) 1913-1918
    CrossrefPubMedGoogle Scholar
  • 5 Chang JY, Antonopoulos DA, Kalra A. , et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis 2008; 197 (03) 435-438
    CrossrefPubMedGoogle Scholar
  • 6 Wilson KH, Perini F. Role of competition for nutrients in suppression of Clostridium difficile by the colonic microflora. Infect Immun 1988; 56 (10) 2610-2614
    CrossrefPubMedGoogle Scholar
  • 7 Le Lay C, Dridi L, Bergeron MG, Ouellette M, Fliss IL. Nisin is an effective inhibitor of Clostridium difficile vegetative cells and spore germination. J Med Microbiol 2016; 65 (02) 169-175
    CrossrefPubMedGoogle Scholar
  • 8 Rea MC, Sit CS, Clayton E. , et al. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile . Proc Natl Acad Sci U S A 2010; 107 (20) 9352-9357
    CrossrefPubMedGoogle Scholar
  • 9 Weingarden AR, Dosa PI, DeWinter E. , et al. Changes in colonic bile acid composition following fecal microbiota transplantation are sufficient to control Clostridium difficile germination and growth. PLoS One 2016; 11 (01) e0147210
    CrossrefPubMedGoogle Scholar
  • 10 Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014; 157 (01) 121-141
    CrossrefPubMedGoogle Scholar
  • 11 Surawicz CM, Brandt LJ, Binion DG. , et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108 (04) 478-498 , quiz 499
    CrossrefPubMedGoogle Scholar
  • 12 McDonald LC, Gerding DN, Johnson S. , et al. Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66 (07) 987-994
    CrossrefPubMedGoogle Scholar
  • 13 Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013; 108 (04) 500-508
    CrossrefPubMedGoogle Scholar
  • 14 Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 2011; 53 (10) 994-1002
    CrossrefPubMedGoogle Scholar
  • 15 Cammarota G, Masucci L, Ianiro G. , et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015; 41 (09) 835-843
    CrossrefPubMedGoogle Scholar
  • 16 Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect 2009; 58 (06) 403-410
    CrossrefPubMedGoogle Scholar
  • 17 Cornely OA, Crook DW, Esposito R. , et al; OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis 2012; 12 (04) 281-289
    CrossrefPubMedGoogle Scholar
  • 18 Cammarota G, Ianiro G, Tilg H. , et al; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017; 66 (04) 569-580
    CrossrefPubMedGoogle Scholar
  • 19 Lee CH, Steiner T, Petrof EO. , et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2016; 315 (02) 142-149
    CrossrefPubMedGoogle Scholar
  • 20 Jiang ZD, Ajami NJ, Petrosino JF. , et al. Randomised clinical trial: faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy. Aliment Pharmacol Ther 2017; 45 (07) 899-908
    CrossrefPubMedGoogle Scholar
  • 21 Staley C, Hamilton MJ, Vaughn BP. , et al. Successful resolution of recurrent Clostridium difficile infection using freeze-dried, encapsulated fecal microbiota; pragmatic cohort study. Am J Gastroenterol 2017; 112 (06) 940-947
    CrossrefPubMedGoogle Scholar
  • 22 Panchal P, Elliott RJ, Budree S. , et al. 1010 - scaling access to fecal microbiota transplantation for recurrent Clostridium difficle infection in the United States: a geospatial time-series analysis from 2013 to 2017. Gastroenterology 2018; 154 (06) (Suppl. 01) S-190-S-191
    PubMedGoogle Scholar
  • 23 Furuya-Kanamori L, Doi SAR, Paterson DL. , et al. Upper versus lower gastrointestinal delivery for transplantation of fecal microbiota in recurrent or refractory Clostridium difficile infection: a collaborative analysis of individual patient data from 14 studies. J Clin Gastroenterol 2017; 51 (02) 145-150
    CrossrefPubMedGoogle Scholar
  • 24 Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P. ; West Midlands Research Collaborative. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg 2012; 99 (11) 1501-1513
    CrossrefPubMedGoogle Scholar
  • 25 Steele SR, McCormick J, Melton GB. , et al. Practice parameters for the management of Clostridium difficile infection. Dis Colon Rectum 2015; 58 (01) 10-24
    CrossrefPubMedGoogle Scholar
  • 26 Kulaylat AS, Kassam Z, Hollenbeak CS, Stewart Sr DB. A surgical Clostridium-associated risk of death score predicts mortality after colectomy for Clostridium difficile . Dis Colon Rectum 2017; 60 (12) 1285-1290
    CrossrefPubMedGoogle Scholar
  • 27 Hensgens MP, Dekkers OM, Goorhuis A, LeCessie S, Kuijper EJ. Predicting a complicated course of Clostridium difficile infection at the bedside. Clin Microbiol Infect 2014; 20 (05) O301-O308
    CrossrefPubMedGoogle Scholar
  • 28 Na X, Martin AJ, Sethi S. , et al. A multi-center prospective derivation and validation of a clinical prediction tool for severe Clostridium difficile infection. PLoS One 2015; 10 (04) e0123405
    CrossrefPubMedGoogle Scholar
  • 29 van der Wilden GM, Chang Y, Cropano C. , et al. Fulminant Clostridium difficile colitis: prospective development of a risk scoring system. J Trauma Acute Care Surg 2014; 76 (02) 424-430
    CrossrefPubMedGoogle Scholar
  • 30 Beauregard-Paultre C, Chakra CNA, McGeer A. , et al. External validation of clinical scores to predict complications of Clostridium difficile infection. Open Forum Infect Dis 2017; 4: S402-S402
    PubMedGoogle Scholar
  • 31 Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg 2011; 254 (03) 423-427 , discussion 427–429
    CrossrefPubMedGoogle Scholar
  • 32 Fashandi AZ, Martin AN, Wang PT. , et al. An institutional comparison of total abdominal colectomy and diverting loop ileostomy and colonic lavage in the treatment of severe, complicated Clostridium difficile infections. Am J Surg 2017; 213 (03) 507-511
    CrossrefPubMedGoogle Scholar
  • 33 Cheng YW, Fischer M. the present status of fecal microbiota transplantation and its value in the elderly. Curr Treat Options Gastroenterol 2017; 15 (03) 349-362
    CrossrefPubMedGoogle Scholar
  • 34 Zainah H, Hassan M, Shiekh-Sroujieh L, Hassan S, Alangaden G, Ramesh M. Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection. Dig Dis Sci 2015; 60 (01) 181-185
    CrossrefPubMedGoogle Scholar
  • 35 Agrawal M, Aroniadis OC, Brandt LJ. , et al. The long-term efficacy and safety of fecal microbiota transplant for recurrent, severe, and complicated Clostridium difficile infection in 146 elderly individuals. J Clin Gastroenterol 2016; 50 (05) 403-407
    CrossrefPubMedGoogle Scholar
  • 36 Weingarden AR, Hamilton MJ, Sadowsky MJ, Khoruts A. Resolution of severe Clostridium difficile infection following sequential fecal microbiota transplantation. J Clin Gastroenterol 2013; 47 (08) 735-737
    CrossrefPubMedGoogle Scholar
  • 37 Fischer M, Sipe BW, Rogers NA. , et al. Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate. Aliment Pharmacol Ther 2015; 42 (04) 470-476
    CrossrefPubMedGoogle Scholar
  • 38 Fischer M, Sipe B, Cheng YW. , et al. Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: a promising treatment approach. Gut Microbes 2017; 8 (03) 289-302
    CrossrefPubMedGoogle Scholar
  • 39 Ianiro G, Masucci L, Quaranta G. , et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions. Aliment Pharmacol Ther 2018; 48 (02) 152-159
    CrossrefPubMedGoogle Scholar
  • 40 Hocquart M, Lagier J-C, Cassir N. , et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis 2018; 66 (05) 645-650
    CrossrefPubMedGoogle Scholar
  • 41 Cammarota G, Ianiro G, Magalini S, Gasbarrini A, Gui D. Decrease in surgery for Clostridium difficile infection after starting a program to transplant fecal microbiota. Ann Intern Med 2015; 163 (06) 487-488
    CrossrefPubMedGoogle Scholar
  • 42 Cheng Y-W, Phelps E, Rogers N. , et al. Fecal Microbiota Transplant Decreases Mortality in Patients with Severe and Severe-Complicated Clostridium difficile Infection, Including Cases Not Eligible for Colectomy. World Congress of Gastroenterology at ACG; 2017 ; Orlando, FL. Clin Gastro Hepato 2020. Epub ahead of print
    PubMedGoogle Scholar
  • 43 Seder CW, Villalba Jr MR, Robbins J. , et al. Early colectomy may be associated with improved survival in fulminant Clostridium difficile colitis: an 8-year experience. Am J Surg 2009; 197 (03) 302-307
    CrossrefPubMedGoogle Scholar
  • 44 Andremont A. Too early to recommend early fecal microbiota transplantation in patients with severe Clostridium difficile infection, or not too early?. Clin Infect Dis 2018; 66 (05) 651-652
    CrossrefPubMedGoogle Scholar
  • 45 Brandt LJ, Borody TJ, Campbell J. Endoscopic fecal microbiota transplantation: “first-line” treatment for severe Clostridium difficile infection?. J Clin Gastroenterol 2011; 45 (08) 655-657
    CrossrefPubMedGoogle Scholar
  • 46 Byar DP, Schoenfeld DA, Green SB. , et al. Design considerations for AIDS trials. N Engl J Med 1990; 323 (19) 1343-1348
    CrossrefPubMedGoogle Scholar
  • 47 Yazdanpanah Y, Horby P, van Griensven J. , et al. Drug assessment in the Ebola virus disease epidemic in west Africa. Lancet Infect Dis 2015; 15 (11) 1258-1258
    PubMedGoogle Scholar
  • 48 Allegretti JR, Kassam Z, Osman M, Budree S, Fischer M, Kelly CR. The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection. Gastrointest Endosc 2018; 87 (01) 18-29
    CrossrefPubMedGoogle Scholar
  • 49 Ananthakrishnan AN, McGinley EL, Saeian K, Binion DG. Temporal trends in disease outcomes related to Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17 (04) 976-983
    CrossrefPubMedGoogle Scholar
  • 50 Jen MH, Saxena S, Bottle A, Aylin P, Pollok RC. Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33 (12) 1322-1331
    CrossrefPubMedGoogle Scholar
  • 51 Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut 2008; 57 (02) 205-210
    CrossrefPubMedGoogle Scholar
  • 52 Fischer M, Kao D, Kelly C. , et al. Fecal microbiota transplantation is safe and efficacious for recurrent or refractory Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis 2016; 22 (10) 2402-2409
    CrossrefPubMedGoogle Scholar
  • 53 Khoruts A, Rank KM, Newman KM. , et al. Inflammatory bowel disease affects the outcome of fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 2016; 14 (10) 1433-1438
    CrossrefPubMedGoogle Scholar
  • 54 Qazi T, Amaratunga T, Barnes EL, Fischer M, Kassam Z, Allegretti JR. The risk of inflammatory bowel disease flares after fecal microbiota transplantation: systematic review and meta-analysis. Gut Microbes 2017; 8 (06) 574-588
    CrossrefPubMedGoogle Scholar
  • 55 Len O, Rodríguez-Pardo D, Gavaldà J. , et al; Spanish Research Network for the Study of Infection in Transplantation. Outcome of Clostridium difficile-associated disease in solid organ transplant recipients: a prospective and multicentre cohort study. Transpl Int 2012; 25 (12) 1275-1281
    CrossrefPubMedGoogle Scholar
  • 56 Gellad ZF, Alexander BD, Liu JK. , et al. Severity of Clostridium difficile-associated diarrhea in solid organ transplant patients. Transpl Infect Dis 2007; 9 (04) 276-280
    CrossrefPubMedGoogle Scholar
  • 57 Boutros M, Al-Shaibi M, Chan G. , et al. Clostridium difficile colitis: increasing incidence, risk factors, and outcomes in solid organ transplant recipients. Transplantation 2012; 93 (10) 1051-1057
    CrossrefPubMedGoogle Scholar
  • 58 Dubberke ER, Burdette SD. ; AST Infectious Diseases Community of Practice. Clostridium difficile infections in solid organ transplantation. Am J Transplant 2013; 13 (Suppl. 04) 42-49
    CrossrefPubMedGoogle Scholar
  • 59 Kelly CR, Ihunnah C, Fischer M. , et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 2014; 109 (07) 1065-1071
    CrossrefPubMedGoogle Scholar
  • 60 Cheng Y-W, Phelps EL, Ganipini V. , et al. Tu1875 - fecal microbiota transplantation for the treatment of clostridium difficile infection is efficacious and safe in solid organ transplant recipients. Am J Transplantation. PMID 300085388
    PubMedGoogle Scholar