Skip to main content

Advertisement

SpringerLink
Log in

Clostridium Difficile Infection: Risk Factors, Diagnosis and Management

  • Colon (C Burke, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Opinion statement

Clostridium difficile infection (CDI) is the leading cause of death due to gastrointestinal infections in the US and is the most common cause of nosocomial diarrhea. The emergence of a hypervirulent strain in the early 2000s has been associated with a dramatic increase in the number and severity of cases in the US, Canada, and several other countries. Most cases are related to antibiotic use, but sporadic cases occur in otherwise healthy individuals with no risk factors. Morbidity and mortality are highest in the elderly. Diagnosis is confirmed by detection of C. difficile toxin in the stools. Treatment should be stratified by severity of disease, with metronidazole use for mild disease cases and vancomycin for severe disease. Recurrent CDI occurs in 10-20 % of cases. A first recurrence can be treated with a ten-day regimen of metronidazole or vancomycin; a second recurrence is best treated by a pulsed regimen of vancomycin. In patients with multiple (three or more) recurrences, fecal microbiota transplant has a high rate of success. The most important methods of prevention are wise antibiotic policies, hand hygiene, isolation, and barrier methods in hospital and long-term care facilities (LCTF) settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. McGlone SM, Bailey RR, Zimmer SM, et al. The economic burden of Clostridium difficile. Clin Microbiol Infect. 2012;18:282–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433–41.

    Article  CAS  PubMed  Google Scholar 

  3. Sambol SP, Merrigan MM, Lyerly D, et al. Toxin gene analysis of a variant strain of Clostridium difficile that causes human clinical disease. Infect Immun. 2000;68:5480–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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). Infect Control Hosp Epidemiol. 2010;31(5):431–55. A guideline from infectious disease specialists about management of CDI.

    Article  PubMed  Google Scholar 

  5. Bauer MP, Kuijper EJ, van Dissel T. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance for Clostridium difficile infection CDI). Clin Microbiol Infect. 2009;15:1067–79.

    Article  CAS  PubMed  Google Scholar 

  6. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478–98. The most recent guidelines for C. difficile management, authored by a multidisciplinary team, including specialists from gastroenterologists, infectious disease and surgery.

    Article  CAS  PubMed  Google Scholar 

  7. Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother. 2014;69(4):881–91.

    Article  CAS  PubMed  Google Scholar 

  8. Dial S, Delaney JA, Barkun AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989–95.

    Article  CAS  PubMed  Google Scholar 

  9. Kwok CS et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011–9.

    Article  CAS  PubMed  Google Scholar 

  10. Janarthanan S et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107(7):1001–10.

    Article  CAS  PubMed  Google Scholar 

  11. Freedberg DE et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol. 2013;108(11):1794–801.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Issa M, Vijayapal A, Graham MB, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:345–51.

    Article  PubMed  Google Scholar 

  13. Jen MH, Saxena S, Bottle A, et al. Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33:1322–31.

    Article  CAS  PubMed  Google Scholar 

  14. Rea MC, O'Sullivan O, Shanahan F, et al. Clostridium difficile carriage in elderly subjects and associated changes in the intestinal microbiota. J Clin Microbiol. 2012;50:867–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Deshpande A, Pasupuleti V, Pant C, et al. Potential value of repeat stool testing for Clostridium difficile stool toxin using enzyme immunoassay? Curr Med Res Opin. 2010;26:2635–41.

    Article  PubMed  Google Scholar 

  16. Shetty N, Wren MW, Coen PG. The role of glutamate dehydrogenase for the detection of Clostridium difficile in faecal samples: a meta-analysis. J Hosp Infect. 2011;77:1–6.

    Article  CAS  PubMed  Google Scholar 

  17. Larson AM, Fung AM, Fang FC. Evaluation of tcdB real-time PCR in a three-step diagnostic algorithm for detection of toxigenic Clostridium difficile. J Clin Microbiol. 2010;48:124–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Fujitani S, George WI, Murthy AR. Comparison of clinical severity score indices for Clostridium difficile infection. Infect Control Hosp Epidemiol. 2011;32:220–8. Prospective evaluation of severity of illness provides guidance on criteria to define severe CDI.

    Article  PubMed  Google Scholar 

  19. Abougergi MS et al. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature. J Hosp Med. 2010;5(1):E1–9.

    Article  PubMed  Google Scholar 

  20. Shen B, Goldblum JR, Hull TL, et al. Clostridium difficile-associated pouchitis. Dig Dis Sci. 2006;51:2361–4.

    Article  PubMed  Google Scholar 

  21. Seril DN, Shen B. Clostridium difficile infection in patients with ileal pouches. Am J Gastroenterol. 2014;109(7):941–7.

    Article  PubMed  Google Scholar 

  22. Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg. 2007;245(2):267–72. Retrospective surgical series defines criteria associated with increased mortality in CDI.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Neal MD, Alverdy JC, Hall DE, et al. 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(3):423–7. discussion 427-9. Novel surgical approach using loop ileostomy instead of subtotal colectomy in patients requiring surgery.

    Article  PubMed  Google Scholar 

  24. Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: the use of high dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis. 2000;31:1012–7.

    Article  CAS  PubMed  Google Scholar 

  25. Bakken JS, Borody T, Brandt LJ, et al. Fecal Microbiota Transplantation (FMT) Workgroup. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044–9.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.

    Article  PubMed  Google Scholar 

  27. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53:994–1002.

    Article  PubMed  Google Scholar 

  28. Guo B, Harstall C, Louie T, Zanten S, Dieleman L (2012) Systematic review: Faecal transplantation for the treatment of Clostridium difficile-associated disease. Aliment Pharmacol Ther.

  29. Hamilton MJ, Weingarden AR, Sadowsky MJ, et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:761–7.

    Article  PubMed  Google Scholar 

  30. Petrof E, Gloor G, Vanner et al (2013) Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 3–3.

  31. Konijeti GG et al. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis. 2014;58(11):1507–14.

    Article  PubMed  Google Scholar 

  32. Owens C, Broussard E, Surawicz CM. Fecal microbiota transplantation and donor standardization. Trends Microbiol. 2013;21:443–5.

    Article  CAS  PubMed  Google Scholar 

  33. Smith M, Kelly C, Alm E (2014) How to regulate faecal transplants. Nature 506(7488)

  34. Schwartz M et al. Norovirus gastroenteritis after fecal microbiota transplantation for treatment of Clostridium difficile infection despite asymptomatic donors and lack of sick contacts. Am J Gastroenterol. 2013;108(8):1367.

    Article  PubMed  Google Scholar 

  35. De Leon LM et al. Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11(8):1036–8.

    Article  PubMed  Google Scholar 

  36. Ihunnah M, Kellu C, Fischer M et al. Fecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Immunocompromised Patients. Am Coll Gastroenterol. 2013.

  37. Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:1079–87.

    Article  PubMed  Google Scholar 

  38. Cornely OA, Crook DW, Esposito R, et al. 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;12:281–9.

    Article  CAS  PubMed  Google Scholar 

  39. Abourgergi MS, Kwon JH. Intravenous immunoglobulin for the treatment of Clostridium difficile infection: a review. Dig Dis Sci. 2011;56:19–26.

    Article  Google Scholar 

  40. Johnson S, Schriever C, Galang M, et al. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis. 2007;44:846–8.

    Article  CAS  PubMed  Google Scholar 

  41. Johnson S, Schriever C, Patel U, et al. Rifaximin redux: treatment of recurrent Clostridium difficile infection with rifaximin immediately post-vancomycin treatment. Anaerobe. 2009;15:290–1.

    Article  CAS  PubMed  Google Scholar 

  42. Garey KW, Jiang ZD, Bellard A, et al. Rifaximin in treatment of recurrent Clostridium difficile-associated diarrhea: an uncontrolled pilot study. J Clin Gastroenterol. 2009;43:91–3.

    Article  PubMed  Google Scholar 

  43. Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol. 2000;95 suppl 1:S11–3.

    Article  CAS  PubMed  Google Scholar 

  44. McFarland LV. Meta-analysis of probiotics for prevention of antibiotic associated diarrhea and treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;1010:812–22.

    Article  Google Scholar 

  45. 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;271:1913–8.

    Article  CAS  PubMed  Google Scholar 

  46. Dellit TH, Owens RC, McGowan Jr JE, et al. Infectious Diseasess Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44:159–77.

    Article  PubMed  Google Scholar 

  47. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention of Clostridium difficile–Associated Diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012;157:878–88. doi:10.7326/0003-4819-157-12-201212180-00563.

    Article  PubMed  Google Scholar 

  48. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicenter trial. Lancet. 2013;382:1249–57.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Christina M. Surawicz declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, University of Washington, 325 9th Ave., Box 359773, Seattle, WA, 98104, USA

    Christina M. Surawicz MD

Authors
  1. Christina M. Surawicz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christina M. Surawicz MD.

Additional information

This article is part of the Topical Collection on Colon

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Surawicz, C.M. Clostridium Difficile Infection: Risk Factors, Diagnosis and Management. Curr Treat Options Gastro 13, 121–129 (2015). https://doi.org/10.1007/s11938-014-0038-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-014-0038-3

Keywords

Search

Navigation