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Pathogenesis and Clinical Manifestations of Clostridium difficile Diarrhea and Colitis

  • R. J. Farrell
  • J. T. LaMont
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 250)

Abstract

Clostridium difficile is a spore-forming, gram-positive anaerobic bacillus discovered in 1935 as a commensal organism in the fecal flora of healthy newborn infants (Hall and O’Toole 1935). The organism was given its name because it grew very slowly in culture and was difficult to isolate in pure culture. Its presence in the stool of 50% of healthy neonates suggested that C. difficile was a commensal not a pathogen, even though it was toxigenic in broth culture. Not long after its original description, C. difficile passed into obscurity until its rediscovery some four decades later. Antibiotic-associated pseudomembranous colitis became prevalent in the 1960s and 1970s with the introduction into clinical practice of broad-spectrum antibiotics. The frequent association of clindamycin and lincomycin therapy with pseudomembranous colitis led to the term “clindamycin colitis” (Tedesco et al. 1974). A breakthrough occurred in 1978 when C. difficile was identified as the source of a cytotoxin found in the stool of patients with pseudomembranous colitis (Bartlett et al. 1978). During the two decades since its rediscovery, a great deal has been learned about the pathophysiology, epidemiology, and management of C. difficile diarrhea, yet many challenges remain. At present this organism continues to infect up to 20% of individuals admitted to hospital, making C. difficile colitis the most common enteric infection in hospital practice (Kelly et al. 1994).

Keywords

Pseudomembranous Colitis Toxic Megacolon Colonic Microflora Fulminant Colitis Osmotic Diarrhea 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anand A, Glatt AE (1993) Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 17: I09Google Scholar
  2. Aronsson B, Molby R, Nord CE (1985) Antimicrobial agents and Clostridium difficile in acute disease: epidemiological data from Sweden, 1984 1982.1 Infect Dis 151: 476Google Scholar
  3. Barbut F, Meynard.IL, Guiget M, Avesani V, Bochet MV, Meyohas MC, Delmee M, Tilleul P, Frottier J, Petit.IC (1997) Clostridium difficile-associated diarrhea in HIV-infected patients: epidemiology and risk factors. J Acquir Immune Delle Syndr Hum Retrovirol 16(3):176–181Google Scholar
  4. Bartlett JG (1981) Antimicrobial agents implicated in Clostridium difficile toxin-associated diarrhea of colitis. Johns Hopkins Med J 149 (1): 6–9PubMedGoogle Scholar
  5. Bartlett J(ì, (’hang TW, Gurwith M, Gorhach SL, Onderdonk AD (1978) Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med 298: 531–534Google Scholar
  6. Bignardi GE (1998) Risk factors for Clostridium difficile infection. J Hosp Infect 40(l):I- 15Google Scholar
  7. Bolton RP, Sherrill RJ, Read AE (1980) Clostridium difficile associated diarrhea: a role in inflammatory bowel disease? Lancet 1: 383 384Google Scholar
  8. Borriello SP (1990) The influence of the normal flora on Clostridium difficile colonisation of the gut. Ann Med 22: 61–67PubMedCrossRefGoogle Scholar
  9. Castagliuolo I, Kcates AC, Wang CC, Pasha A, Valenick L, Kelly CI’. Nikulasson ST, LaMont JT, Pothoulakis C (1998) Clostridium difficile toxin A stimulates macrophage-inflammatory protein-2 production in rat intestinal epithelial cells. J Immunol 160(12):6039–6045Google Scholar
  10. Do AN, Fridkin SK, Yechouron A, Banerjec SN. Killgore GE, Bourgault AM, Jolivet M, Jarvis WR (1998) Risk factors for early recurrent Clostridium difficile-associated diarrhea. Clin Infect Dis 26(4): 954 959Google Scholar
  11. Fekety R, King KH. Brown D, Batts DEI, Cudmore M, Silva Jr J (1981) Epidemiology of antibiotic-associated colitis; isolation of Clostridium difficile from the hospital environment. Am J Med 70:906–908Google Scholar
  12. Fekerty R, McFarland LV, Surawiez CM, Greenberg RN, Elmer GW, Mulligan ME (1997) Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis 24 (3): 324–333CrossRefGoogle Scholar
  13. Fishman E, Kavuru M, Jones B, Kuhlman,LE, Merine DS, Lillimore KD, Siegelman SS (1991) CT of pseudomembranous colitis: Radiologie, clinical, and pathologic correlation. Radiology 180: 157 161Google Scholar
  14. Freiman JP, Graham DJ, Green L(1989) Pseudomembranous colitis associated with single-dose cephalo-sporin prophylaxis. JAMA 262(7):902Google Scholar
  15. Golledge CL, McKenzie T, and Riley TV (1989) Extended spectrum cephalosporins and Clostridium difficile. J Antitnicroh Chemother 23: 929–931CrossRefGoogle Scholar
  16. Hall IC, O’Toole E (1935) Intestinal flora in newborn infants with description of a new pathogenic anaerobe. Am.1 Dis Child 49: 390–402Google Scholar
  17. Hecht G, Koutsouris A, Pothoulakis C, LaMont JT, Madam,IL (1992) Clostridium cli/ficile toxin B disrupts the harrier function of T84 monolaycrs. Gastroenterology 102: 416–423Google Scholar
  18. Hirschhorn LR, Trnka Y, Onderdonk A, Lee ML, Platt R (1994) Epidemiology ofconununily-acquired Clostridium difficile-associated diarrhea. J Infect Dis 169: 127 133Google Scholar
  19. Hornbuckle K, Chak A, Lazarus HM, Cooper GS, Kutteh LA, Gucalp R, Carlisle PS, Sparano J. Parker P, Salata RA (1998) Determination and validation of a predictive model for (dos/rid/um difici/e diarrhea in hospitalized oncology patients. Ann Oncol 9 (3): 307–311PubMedCrossRefGoogle Scholar
  20. Jafri SF, Marshall JB (1996) Ascites associated with antibiotic-associated pscudomembranous colitis. South Med J 89 (10): 1014–1017PubMedCrossRefGoogle Scholar
  21. Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR. Gerling DN (1990a) Nosocomial Clostridium difficile colonisation and disease. Lancet 336:97–100Google Scholar
  22. Johnson S, Gerding DN, Olson MM, Weiler MD. Hughes RA, Clabots (’.R, Peterson FR (1990ó) Prospective, controlled study of vinyl glove use to interrupt Clostridium dì%/ui/e nosocomial transmission. Am J Med 88: 137–140Google Scholar
  23. Just 1, Selzer.1, Wilm M, von Eichel-Streiher C, Mann M, Aktories K (1995a) Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375: 500–503Google Scholar
  24. Just 1, Wilm M, Selzer J, Rex G, von Eichel-Streiher C. Mann M, Aktories K (19950) The enleroto.xin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins..1 Biol Chain 270: 13932 13936Google Scholar
  25. Keates AC, Castagliuolo I, Qiu B, N1kulasson S, Sengupta A. Pothoulakis (’ (1998) (’(iRP upregalation in dorsal root ganglia and ileal mucosa during (Ynstridium difficile toxin A-induced enteritis. Am J Physiol 274(I Pt 1 TG 196–202Google Scholar
  26. Kelly CP, Pothoulakis C, Orellana J, LaMont JT (1992) Human colonic aspirates containing immunoglobulin A antibody to Clostridium dif/ici/e toxin A inhibit toxin A-receptor binding. Gastroenterology I(12: 35–40Google Scholar
  27. Kelly CP, LaMont JT (1993) Treatment of Clostridium difficile diarrhea and colitis. In: Wolfe. MM (ed) Gastrointestinal Pharmacotherapy. pp 199–212. Philadelphia: SaundersGoogle Scholar
  28. Kelly CP, Becker S, E.inevsky JK, Joshi MA, O’Keane IC, Dickey 1W. LaMont J’E. Pothoulakis C (1994ä) Neutrophil recruitment in Clostridium di/fie/ 1 /e toxin A enteritis in the rabbit..1 (’lin Ltvest 93(3):1257–1265Google Scholar
  29. Kelly CP, Pothoulakis C, LaMont JT (19940) Clostridium dificily colitis. N Engl J Med 330:257 262 Kelly CP (1996) Immune response to Clostridium c/ifficile’ infection. Fur J Gastroenterol Hepalol 8: 1048 1053Google Scholar
  30. Kim KH, Fekety R, Batts DH, Brown D, Cudmore M, Silva.Jr J, Waters D (1981) Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis 143: 42–50.PubMedCrossRefGoogle Scholar
  31. Kim KH, DuPont HL, Pickering LK (1983) Outbreaks of diarrhea associated with Clostridium di%/icily and its toxin in day-care centers: Evidence of person-to-person spread..J Pediatr 1(12:376Google Scholar
  32. Kim KH laconis JP, Rolfe RD (1987) Immunization of adult hamsters against Clmtridium dt//ui/e-associated ileocecitis and transfer of protection to infant hamsters. Infect Immun 55: 2984–29912Google Scholar
  33. Kralovich KA, Sacsner J, Karmy-,Jones RA, Eggenberger.IC (1997) Pseudomemhranous colitis with associated fulminant ileitis in the defunctionalized limb of a jejunal-ileal bypass: case report. Dis Colon Rectum 40 (5): 622–4Google Scholar
  34. LaMont JT, Trnka YM (1980) Therapeutic implications of Clostridium difficile toxin during relapse of chronic inflammatory bowel disease. Lancet 1: 381–383PubMedCrossRefGoogle Scholar
  35. Larson HE, Barclay FE, Honour P, Hill ID (1982) Epidemiology of Clostridium difficile in infants. J Infect Dis 146: 727PubMedCrossRefGoogle Scholar
  36. Leung DY, Kelly CP, Boguniewicz M, Pothoulakis C. LaMont TI’, Flores A (1991) Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 118: 633–637PubMedCrossRefGoogle Scholar
  37. Libby JM,.lortner BS, Wilkins TD (1982) Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. Infect Immun 36: 822–829Google Scholar
  38. Marx CE, Morris A, Wilson ML, Reiter LB (1993) Fecal leukocytes ni stool specimens submitted for Clostridium difficile toxin assay. Diagn Microhiol Infect Dis 16 (4): 313–315CrossRefGoogle Scholar
  39. McFarland LV, Mulligan ME, Kwok RY, Stamm WE (1989) Nosocomial acquisition of Clostridium difficile infection. N Eng1 J Med 320: 204–210CrossRefGoogle Scholar
  40. McFarland LV, Surawicz (’M, Stamm WE (1990) Risk factors for Clostridium difficile carriage and C. diffici/e-associated diarrhea in a cohort of hospitalized patients. Infect Dis 162: 678–684Google Scholar
  41. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer (ìW, Moyer KA, Melcher SA, Bowen SE, Cox IL, Noorani Z (1994) A randomized placebo-controlled trial of Sorchurunncev boulai - dii in combination with standard antibiotics for Clostridium difficile disease. JAMA 271: 1913–1918Google Scholar
  42. Morris LL, Villalba MR, Glover JL (1994) Management of pseudomembranous colitis. Am Surg 60: 548–552PubMedGoogle Scholar
  43. Mulligan ME, Miller SD, McFarland LV, Fung HC, Kwok RY (1993) Elevated levels of serum im-munoglobulins in asymptomatic carriers of Clostridium difficile. Clin Infect Dis 16 Suppl 4: 5239–244Google Scholar
  44. Nolan NP, Kelly CP, Humphreys JF, Cooney C, O’Connor R, Walsh TN, Weir DG, O’Briain DS (1987) An epidemic of pseudomembranous colitis: importance of person to person spread. Gut 28: 1467–1473PubMedCrossRefGoogle Scholar
  45. Pothoulakis C (1996) Pathogenesis of Clostridium dfficile-associated diarrhoea. Eur J Gastroenterol flepatol 8: 1041–1047CrossRefGoogle Scholar
  46. Pothoulakis C, Castagliuolo I, LaMont JT (1998) Neurons and mast cells modulate secretory and inflammatory responses to enterotoxins. News in Physiological Sciences 13: 58–63PubMedGoogle Scholar
  47. Price AB, Davies DR (1977) Pseudomembranous colitis. J Clin Pathol 30: 1 - I2PubMedCrossRefGoogle Scholar
  48. Ramaswamy R, Grover H, Corpuz M, Daniels P, Pitchumoni CS (1996) Prognostic criteria in Clostridium difficile colitis. Am J Gastroenterol 91 (3): 460–464PubMedGoogle Scholar
  49. Rao SS, Edwards CA, Austen CJ, Bruce C, Reed NW (1988) Impaired colonic fermentation of carbohydrates after ampicillin. Gastroenterology 94 (4): 928–932PubMedGoogle Scholar
  50. Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Zacherl J, Bischof G, Cosentini E, Feil W, Schiessel R, LaMont JT (1995) Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro..1 Clin Invest 95: 2004–2011Google Scholar
  51. Rubin MS, Bodenstein LE, Kent KC’ (1995) Severe Clostridium difficile colitis. Dis Colon Rectum 38: 350–354PubMedCrossRefGoogle Scholar
  52. Saginur R, Hawley CR, Bartlett JG (1980) Colitis associated with metronidazole therapy. J Infect Dis 141: 772–774PubMedCrossRefGoogle Scholar
  53. Salcedo J, Keaces S, Pothoulakis C, Castagliuolo I, LaMont JT, Kelly CP (1997) Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 41 (3): 366–370PubMedCrossRefGoogle Scholar
  54. Shim JK, Johnson S, Samore MH, Bliss DZ, Gerding DN (1998) Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhea. Lancet 351 (9103): 633–6PubMedCrossRefGoogle Scholar
  55. Shortland JR, Spencer RC, Williams JL (1983) Pseudomembranous colitis associated with changes in an ileal conduit. J Clin Pathol 36 (10): 1184–7PubMedCrossRefGoogle Scholar
  56. Snyder ML (1940) The normal fecal flora between two weeks and one year of age: serial studies. J Infect Dis 65: 1CrossRefGoogle Scholar
  57. Tedesco FJ, Barton RW, Alpers DH (1974) Clindamycin-associated colitis. A prospective study. Ann Intern Med 81: 429–433Google Scholar
  58. Tedesco Fi, Corless JK, Brownstein RE (1982) Rectal sparing in antibiotic-associated pseudomembranous colitis: a prospective study. Gastroenterology 83: 1259–1260PubMedGoogle Scholar
  59. Thomson G, Clark ALI, Hare K, Spilg WG (1981) Pseudomembranous colitis after treatment with metronidazole. Br Med J 282: 864–865CrossRefGoogle Scholar
  60. Truong M, Atri M, Bret PM, Reinhold C, Kintzen G, Thibodeau M, Aldis AE, Chang Y (1998) Sonographie appearances of benign and malignant conditions of the colon. Am J Roentgenol 170 (6): 1451–1455CrossRefGoogle Scholar
  61. Tsutaoka B, Hansen J, Johnson D, Holodniy M (1994) Antibiotic-associated pseudomembranous enteritis due to Clostridium difficile. Clin Infect Dis 18 (6): 982–984PubMedCrossRefGoogle Scholar
  62. Tvede M, Rask-Madsen J (1989) Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1: 1156–1160PubMedCrossRefGoogle Scholar
  63. Viscidi R, Bartlett JG (1981) Antibiotic-associated pseudomembranous colitis in children. Pediatrics 67: 381PubMedGoogle Scholar
  64. Viscidi R, Willey S, Bartlett JG (1981) Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 81: 5–9PubMedGoogle Scholar
  65. Viscidi R, Laughon BE, Yolken R, Bo-Linn P, Moench T, Ryder RW, Bartlett JG (1983) Serum antibody response to toxins A and B of Clostridium dr}f’rlle. J Infect Dis 148: 93–100PubMedCrossRefGoogle Scholar
  66. Von Eichel-Streiber C, Boquet P, Souerborn M, Thalestam M (1996) Large clostridial cytotoxins-a family of glycosyltransferases modifying small GTP-binding proteins. Trnds Microhiol 4 (l0): 375–382CrossRefGoogle Scholar
  67. Warny M, Vaerman JP, Avesani V, Delmee M (1994) Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun 62: 384–389PubMedGoogle Scholar
  68. Welch DE, Marks MI (1982) Is Clostridium difficile pathogenic in infants’? J Paediatrics 100:392 Wershil BK, Castagliuolo I, Pothoulakis C (1998) Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. Gastroenterology 114 (5): 956–964Google Scholar
  69. Zuckerman E, Kanel G, Ha C, Kahn J, Gottesman BS, Korula J (1997) Low albumin gradient ascites complicating severe pseudomembranous colitis. Gastroenterology 112 (3): 991–994PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • R. J. Farrell
    • 1
  • J. T. LaMont
    • 1
  1. 1.Division of GastroenterologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA

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