Skip to main content
Canadian Family Physician logoLink to Canadian Family Physician
. 2004 Nov;50:1536-40, 1543-5.

Clostridium difficile-associated colitis.

Mark W Hull 1, Paul L Beck 1
PMCID: PMC2214524  PMID: 15597970

Abstract

OBJECTIVE: To review the basic microbiology, pathogenesis of disease, and diagnosis of the nosocomial pathogen Clostridium difficile and to examine therapies recommended by the Canadian Task Force on Preventive Health Care. QUALITY OF EVIDENCE MEDLINE: was searched using MeSH headings. Controlled trials for therapy were sought, but case-control studies and observational reviews were included. MAIN MESSAGE: Clostridium difficile causes approximately 20% of cases of diarrhea associated with antibiotics, including clindamycin and the second- and third-generation cephalosporins. Diarrhea is usually mild, but can be severe; extreme cases develop toxic megacolon. Diagnosis is dependent on demonstrating presence of clostridial toxin in stool specimens or of pseudomembranes through sigmoidoscopy. First-line therapy for C. difficile diarrhea is restricted to metronidazole. Second-line therapy for treatment failure is vancomycin. For relapse, a second course of metronidazole is recommended; tapering courses of vancomycin and probiotics are used for multiple recurrences. CONCLUSION: Clostridium difficile is an important nosocomial pathogen requiring prudent use of antibiotics and strict infection-control policies to prevent large health care costs.

Full Text

The Full Text of this article is available as a PDF (327.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alfa M. J., Kabani A., Lyerly D., Moncrief S., Neville L. M., Al-Barrak A., Harding G. K., Dyck B., Olekson K., Embil J. M. Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile-associated diarrhea. J Clin Microbiol. 2000 Jul;38(7):2706–2714. doi: 10.1128/jcm.38.7.2706-2714.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anand A., Glatt A. E. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis. 1993 Jul;17(1):109–113. doi: 10.1093/clinids/17.1.109. [DOI] [PubMed] [Google Scholar]
  3. Bartlett J. G. Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism. Clin Infect Dis. 1994 May;18 (Suppl 4):S265–S272. doi: 10.1093/clinids/18.supplement_4.s265. [DOI] [PubMed] [Google Scholar]
  4. Bartlett John G. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334–339. doi: 10.1056/NEJMcp011603. [DOI] [PubMed] [Google Scholar]
  5. Bolton R. P., Culshaw M. A. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut. 1986 Oct;27(10):1169–1172. doi: 10.1136/gut.27.10.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Buggy B. P., Fekety R., Silva J., Jr Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomycin and rifampin. J Clin Gastroenterol. 1987 Apr;9(2):155–159. doi: 10.1097/00004836-198704000-00009. [DOI] [PubMed] [Google Scholar]
  7. Clabots C. R., Johnson S., Olson M. M., Peterson L. R., Gerding D. N. Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis. 1992 Sep;166(3):561–567. doi: 10.1093/infdis/166.3.561. [DOI] [PubMed] [Google Scholar]
  8. Cleary R. K. Clostridium difficile-associated diarrhea and colitis: clinical manifestations, diagnosis, and treatment. Dis Colon Rectum. 1998 Nov;41(11):1435–1449. doi: 10.1007/BF02237064. [DOI] [PubMed] [Google Scholar]
  9. Cronberg S., Castor B., Thorén A. Fusidic acid for the treatment of antibiotic-associated colitis induced by Clostridium difficile. Infection. 1984 Jul-Aug;12(4):276–279. doi: 10.1007/BF01645961. [DOI] [PubMed] [Google Scholar]
  10. Dudley M. N., McLaughlin J. C., Carrington G., Frick J., Nightingale C. H., Quintiliani R. Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial. Arch Intern Med. 1986 Jun;146(6):1101–1104. [PubMed] [Google Scholar]
  11. Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 1997 May;92(5):739–750. [PubMed] [Google Scholar]
  12. Fekety R., McFarland L. V., Surawicz C. M., Greenberg R. N., Elmer G. W., Mulligan M. E. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997 Mar;24(3):324–333. doi: 10.1093/clinids/24.3.324. [DOI] [PubMed] [Google Scholar]
  13. Fekety R., Silva J., Kauffman C., Buggy B., Deery H. G. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med. 1989 Jan;86(1):15–19. doi: 10.1016/0002-9343(89)90223-4. [DOI] [PubMed] [Google Scholar]
  14. Gebhard R. L., Gerding D. N., Olson M. M., Peterson L. R., McClain C. J., Ansel H. J., Shaw M. J., Schwartz M. L. Clinical and endoscopic findings in patients early in the course of clostridium difficile-associated pseudomembranous colitis. Am J Med. 1985 Jan;78(1):45–48. doi: 10.1016/0002-9343(85)90460-7. [DOI] [PubMed] [Google Scholar]
  15. Gerding D. N. Disease associated with Clostridium difficile infection. Ann Intern Med. 1989 Feb 15;110(4):255–257. doi: 10.7326/0003-4819-110-4-255. [DOI] [PubMed] [Google Scholar]
  16. Gerding D. N., Johnson S., Peterson L. R., Mulligan M. E., Silva J., Jr Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995 Aug;16(8):459–477. doi: 10.1086/648363. [DOI] [PubMed] [Google Scholar]
  17. Jacobs A., Barnard K., Fishel R., Gradon J. D. Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 2001 Mar;80(2):88–101. doi: 10.1097/00005792-200103000-00002. [DOI] [PubMed] [Google Scholar]
  18. Jobe B. A., Grasley A., Deveney K. E., Deveney C. W., Sheppard B. C. Clostridium difficile colitis: an increasing hospital-acquired illness. Am J Surg. 1995 May;169(5):480–483. doi: 10.1016/S0002-9610(99)80199-8. [DOI] [PubMed] [Google Scholar]
  19. Johnson S., Samore M. H., Farrow K. A., Killgore G. E., Tenover F. C., Lyras D., Rood J. I., DeGirolami P., Baltch A. L., Rafferty M. E. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med. 1999 Nov 25;341(22):1645–1651. doi: 10.1056/NEJM199911253412203. [DOI] [PubMed] [Google Scholar]
  20. Kelly C. P., Pothoulakis C., LaMont J. T. Clostridium difficile colitis. N Engl J Med. 1994 Jan 27;330(4):257–262. doi: 10.1056/NEJM199401273300406. [DOI] [PubMed] [Google Scholar]
  21. Kuijper E. J., de Weerdt J., Kato H., Kato N., van Dam A. P., van der Vorm E. R., Weel J., van Rheenen C., Dankert J. Nosocomial outbreak of Clostridium difficile-associated diarrhoea due to a clindamycin-resistant enterotoxin A-negative strain. Eur J Clin Microbiol Infect Dis. 2001 Aug;20(8):528–534. doi: 10.1007/s100960100550. [DOI] [PubMed] [Google Scholar]
  22. Kyne L., Farrell R. J., Kelly C. P. Clostridium difficile. Gastroenterol Clin North Am. 2001 Sep;30(3):753-77, ix-x. doi: 10.1016/s0889-8553(05)70209-0. [DOI] [PubMed] [Google Scholar]
  23. Larson H. E., Barclay F. E., Honour P., Hill I. D. Epidemiology of Clostridium difficile in infants. J Infect Dis. 1982 Dec;146(6):727–733. doi: 10.1093/infdis/146.6.727. [DOI] [PubMed] [Google Scholar]
  24. Levy D. G., Stergachis A., McFarland L. V., Van Vorst K., Graham D. J., Johnson E. S., Park B. J., Shatin D., Clouse J. C., Elmer G. W. Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting. Clin Ther. 2000 Jan;22(1):91–102. doi: 10.1016/s0149-2918(00)87980-1. [DOI] [PubMed] [Google Scholar]
  25. Lyerly D. M., Neville L. M., Evans D. T., Fill J., Allen S., Greene W., Sautter R., Hnatuck P., Torpey D. J., Schwalbe R. Multicenter evaluation of the Clostridium difficile TOX A/B TEST. J Clin Microbiol. 1998 Jan;36(1):184–190. doi: 10.1128/jcm.36.1.184-190.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McFarland L. V., Mulligan M. E., Kwok R. Y., Stamm W. E. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. 1989 Jan 26;320(4):204–210. doi: 10.1056/NEJM198901263200402. [DOI] [PubMed] [Google Scholar]
  27. McFarland L. V., Surawicz C. M., Greenberg R. N., Fekety R., Elmer G. W., Moyer K. A., Melcher S. A., Bowen K. E., Cox J. L., Noorani Z. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994 Jun 22;271(24):1913–1918. [PubMed] [Google Scholar]
  28. McFarland Lynne V., Elmer Gary W., Surawicz Christina M. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002 Jul;97(7):1769–1775. doi: 10.1111/j.1572-0241.2002.05839.x. [DOI] [PubMed] [Google Scholar]
  29. Merz C. S., Kramer C., Forman M., Gluck L., Mills K., Senft K., Steiman I., Wallace N., Charache P. Comparison of four commercially available rapid enzyme immunoassays with cytotoxin assay for detection of Clostridium difficile toxin(s) from stool specimens. J Clin Microbiol. 1994 May;32(5):1142–1147. doi: 10.1128/jcm.32.5.1142-1147.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mitchell T. J., Ketley J. M., Burdon D. W., Candy D. C., Stephen J. Biological mode of action of Clostridium difficile toxin A: a novel enterotoxin. J Med Microbiol. 1987 May;23(3):211–219. doi: 10.1099/00222615-23-3-211. [DOI] [PubMed] [Google Scholar]
  31. Morris J. B., Zollinger R. M., Jr, Stellato T. A. Role of surgery in antibiotic-induced pseudomembranous enterocolitis. Am J Surg. 1990 Nov;160(5):535–539. doi: 10.1016/s0002-9610(05)81024-4. [DOI] [PubMed] [Google Scholar]
  32. Nelson D. E., Auerbach S. B., Baltch A. L., Desjardin E., Beck-Sague C., Rheal C., Smith R. P., Jarvis W. R. Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins. Infect Control Hosp Epidemiol. 1994 Feb;15(2):88–94. doi: 10.1086/646867. [DOI] [PubMed] [Google Scholar]
  33. Olson M. M., Shanholtzer C. J., Lee J. T., Jr, Gerding D. N. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol. 1994 Jun;15(6):371–381. doi: 10.1086/646934. [DOI] [PubMed] [Google Scholar]
  34. Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol. 2000 Jan;95(1 Suppl):S11–S13. doi: 10.1016/s0002-9270(99)00809-6. [DOI] [PubMed] [Google Scholar]
  35. Pothoulakis C. Pathogenesis of Clostridium difficile-associated diarrhoea. Eur J Gastroenterol Hepatol. 1996 Nov;8(11):1041–1047. doi: 10.1097/00042737-199611000-00003. [DOI] [PubMed] [Google Scholar]
  36. Riegler M., Sedivy R., Pothoulakis C., Hamilton G., Zacherl J., Bischof G., Cosentini E., Feil W., Schiessel R., LaMont J. T. Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest. 1995 May;95(5):2004–2011. doi: 10.1172/JCI117885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Synnott K., Mealy K., Merry C., Kyne L., Keane C., Quill R. Timing of surgery for fulminating pseudomembranous colitis. Br J Surg. 1998 Feb;85(2):229–231. doi: 10.1046/j.1365-2168.1998.00519.x. [DOI] [PubMed] [Google Scholar]
  38. Teasley D. G., Gerding D. N., Olson M. M., Peterson L. R., Gebhard R. L., Schwartz M. J., Lee J. T., Jr Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov 5;2(8358):1043–1046. doi: 10.1016/s0140-6736(83)91036-x. [DOI] [PubMed] [Google Scholar]
  39. Tedesco F. J., Gordon D., Fortson W. C. Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis. Am J Gastroenterol. 1985 Nov;80(11):867–868. [PubMed] [Google Scholar]
  40. Triadafilopoulos G., Hallstone A. E. Acute abdomen as the first presentation of pseudomembranous colitis. Gastroenterology. 1991 Sep;101(3):685–691. doi: 10.1016/0016-5085(91)90526-q. [DOI] [PubMed] [Google Scholar]
  41. Tvede M., Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet. 1989 May 27;1(8648):1156–1160. doi: 10.1016/s0140-6736(89)92749-9. [DOI] [PubMed] [Google Scholar]
  42. Wanahita Anna, Goldsmith Elizabeth A., Musher Daniel M. Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile. Clin Infect Dis. 2002 May 23;34(12):1585–1592. doi: 10.1086/340536. [DOI] [PubMed] [Google Scholar]
  43. Warny M., Keates A. C., Keates S., Castagliuolo I., Zacks J. K., Aboudola S., Qamar A., Pothoulakis C., LaMont J. T., Kelly C. P. p38 MAP kinase activation by Clostridium difficile toxin A mediates monocyte necrosis, IL-8 production, and enteritis. J Clin Invest. 2000 Apr;105(8):1147–1156. doi: 10.1172/JCI7545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wenisch C., Parschalk B., Hasenhündl M., Hirschl A. M., Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996 May;22(5):813–818. doi: 10.1093/clinids/22.5.813. [DOI] [PubMed] [Google Scholar]
  45. Young G. P., Ward P. B., Bayley N., Gordon D., Higgins G., Trapani J. A., McDonald M. I., Labrooy J., Hecker R. Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Gastroenterology. 1985 Nov;89(5):1038–1045. doi: 10.1016/0016-5085(85)90206-9. [DOI] [PubMed] [Google Scholar]
  46. de Lalla F., Nicolin R., Rinaldi E., Scarpellini P., Rigoli R., Manfrin V., Tramarin A. Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. Antimicrob Agents Chemother. 1992 Oct;36(10):2192–2196. doi: 10.1128/aac.36.10.2192. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

RESOURCES