Skip to main content Accessibility help

The emergence of Clostridium difficile as a pathogen of food animals

  • J. Glenn Songer (a1)


Clostridium difficile causes pseudomembranous colitis in humans, usually after disruption of the bowel flora by antibiotic therapy. Factors mediating the frank disease include the dose and toxigenicity of the colonizing strain, its ability to adhere to colonic epithelium, the concurrent presence of organisms that affect multiplication and toxin production or activity, and the susceptibility of the host. Toxins A (an enterotoxin) and B (a cytotoxin) play the major role in pathogenesis and the detection of toxins in gut contents is the gold standard for diagnosis. Disease in horses takes the form of often-fatal foal hemorrhagic enteritis. Nosocomial, antibiotic-associated, disease is increasingly common in adult horses. Enteric clinical signs are reported in ostriches, companion animals and recently calves. Clostridium difficile colitis is now a common diagnosis in neonatal pigs in the USA and elsewhere. Clinical features include onset at 1–5 days of age, sometimes with dyspnea, mild abdominal distension and scrotal edema, and commonly with yellow, pasty diarrhea. There is mesocolonic edema grossly, with microscopic diffuse colitis, mucosal edema, crypt distension, epithelial necrosis and superficial mucosal erosion. Neutrophil infiltration of the lamina propria is common, and fibrin and numerous rod-shaped bacteria are observed on the surface. About two-thirds of litters and one-third of piglets will be affected (based upon positive toxin tests), although this appears to vary with the season. The case fatality rate is probably low if considering only direct effects of C. difficile infection. The significance of toxin-positive non-diarrheic pigs and the nature of the interaction of toxins A and B with enterocytes are unknown. Given the widespread occurrence of the disease, there is substantial effort to develop immunoprophylactic products.


Corresponding author


Hide All
Aktories, K (1997a). Bacterial toxins that target Rho proteins. Journal of Clinical Investigation 99: 827829.
Aktories, K (1997b). Rho proteins: targets for bacterial toxins. Trends in Microbiology 5: 282288.
Aldeen, WE, Bingham, M, Aiderzada, A, Kucera, J, Jense, S and Carroll, KC (2000). Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools. Diagnostic Microbiology and Infectious Disease 36: 211213.
Alfa, MJ, Kabani, A, Lyerly, D, Moncrief, S, Neville, LM, Al-Barrak, A, Harding, GK, Dyck, B, Olekson, K and Embil, JM (2000). Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile -associated diarrhea. Journal of Clinical Microbiology 38: 27062714.
Allo, M, Silva, J, Fekety, R, Rifkin, GD and Waskin, H (1979). Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin [sound recording]. Gastroenterology (Glendale, Calif.) 76: 351355.
Aronsson, B, Granstrom, M, Mollby, R and Nord, CE (1985). Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. Infection 13: 97101.
Barbut, F, Richard, A, Hamadi, K, Chomette, V, Burghoffer, B and Petit, JC (2000). Epidemiology of recurrences or reinfections of Clostridium difficile -associated diarrhea. Journal of Clinical Microbiology 38: 23862388.
Bartlett, JG (1992). Antibiotic-associated diarrhea. Clinical Infectious Diseases 15: 573581.
Bartlett, JG, Onderdonk, AB and Cinseros, RL (1977). Clindamycin-associated colitis due to a toxin-producing species of clostridium in hamsters. Journal of Infectious Diseases 136: 701705.
Bartlett, JG, Chang, TTW, Gurwith, M, Gorbach, SL and Onderdonk, AB (1978). Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. New England Journal of Medicine 298: 531534.
Bongaerts, GP and Lyerly, DM (1994). Role of toxins A and B in the pathogenesis of Clostridium difficile disease. Microbial Pathogenesis 17: 112.
Borriello, SP and Wilcox, MH (1998). Clostridium difficile infections of the gut: the unanswered questions. Journal of Antimicrobial Chemotherapy 41 Supplement C: 6769.
Braun, V, Hundsberger, T, Leukel, P, Sauerborn, M and von Eichel-Streiber, C (1996). Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene 181: 2938.
Corthier, G, Muller, MC, Wilkins, TD, Lyerly, D, L'Haridon, R (1991). Protection against experimental pseudomembranes colitis in gnotobiotic mice by use of monoclonal antibodies against Clostridium difficile toxin A. Infection and Immunity 59: 11921195.
Fekety, R and Shah, AB (1993). Diagnosis and treatment of Clostridium difficile colitis. Journal of the American Medical Association 269: 7175.
Fekety, R, Kim, KH, Brown, D, Batts, DH, Cudmore, M, Silva, J Jr (1981). Epidemiology of antibiotic-associated colitis: isolation of Clostridium difficile from the hospital environment. American Journal of Medicine 70: 906908.
Fekety, R, McFarland, LV, Surawicz, CM, Greenberg, RN, Elmer, GW and Mulligan, ME (1997). Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients in a prospective, randomized, double-blinded trial. Clinical Infectious Diseases 24: 324333.
Frey, SM and Wilkins, TD (1992). Localization of two epitopes recognized by monoclonal antibody PCG-4 on Clostridium difficile toxin A. Infection and Immunity 60: 24882492.
Giannasca, PJ, Zhang, Z-X, Lei, W-D, Boden, JA, Giel, MA, Monath, TP, Thomas, WD Jr (1999). Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters. Infection and Immunity 67: 527538.
Johnson, D, Clabots, CR and Linn, FV (1990). Nosocomial Clostridium difficile colonisation and disease. Lancet 336: 97100.
Johnson, S and Gerding, DN (1998). Clostridium difficile -associated diarrhea. Clinical Infectious Diseases 26: 10271036.
Johnson, S, Samore, MH and Farrow, KA (1999). Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. New England Journal of Medicine 341: 16451651.
Jones, MA and Hunter, D (1983). Isolation of Clostridium difficile from pigs. Veterinary Record 112: 253.
Kelly, CP and LaMont, JT (1998). Clostridium difficile infection. Annual Review of Medicine 49: 375390.
Kelly, CP, Pothoulakis, C, Orellana, J and LaMont, JT (1992). Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A–receptor binding. Gastroenterology 102: 3540.
Kelly, CP, Pothoulakis, C and LaMont, JT (1994). Clostridium difficile colitis. New England Journal of Medicine 330: 257262.
Kelly, CP, Pothoulakis, C and Vavva, F (1996). Anti- Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins. Antimicrobial Agents and Chemotherapy 40: 373379.
Kelly, CP, Chetham, S and Keates, S (1997). Survival of anti- Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract. Antimicrobial Agents and Chemotherapy 41: 236241.
Ketley, JM, Mitchell, TJ, Candy, DC, Burdon, DW and Stephen, J (1987). The effects of Clostridium difficile crude toxins and toxin A on ileal and colonic loops in immune and non-immune rabbits. Journal of Medical Microbiology 24: 4152.
Kim, PH, Iaconis, JP and Rolfe, RD (1987). Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infection and Immunity 55: 29842992.
Kink, JA and Williams, JA (1998). Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile -associated disease in a hamster model of infection. Infection and Immunity 66: 20182025.
Klipfel, AA, Schein, M, Fahoum, B and Wise, L (2000). Acute abdomen and Clostridium difficile colitis: still a lethal combination. Digestive Surgery 17: 160163.
Kyne, L, Warny, M, Qamar, A and Kelly, CP (2000). Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. New England Journal of Medicine 342: 390397.
Kyne, L, Warny, M and Qamar, A (2001). Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357: 189193.
Larson, HE, Parry, JV, Price, AB, Davies, DR and Tyrrell, DA (1977). Underdescribed toxin in pseudomembranous colitis. British Medical Journal 1: 12461248.
Leung, DY, Kelly, CP and Boguniewicz, M (1991). Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. Journal of Pediatrics 118: 633637.
Limaye, AP, Turgeon, DK, Cookson, BT and Fritsche, TR (2000). Pseudomembranous colitis caused by a toxin A(–) B(+) strain of Clostridium difficile. Journal of Clinical Microbiology 38: 16961697.
Lyerly, DM, Frey, SM and Wilkins, TD (1990). Vaccination against lethal Clostridium difficile enteritis with a nontoxigenic recombinant peptide of toxin A. Current Microbiology 21: 2933.
Lyerly, DM, Bostwick, EF, Binion, SB and Wilkins, TD (1991). Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate. Infection and Immunity 59: 22152218.
McFarland, LV, Mulligan, ME, Kwok, RY and Stamm, WE (1989). Nosocomial acquisition of Clostridium difficile infection. New England Journal of Medicine 320: 204210.
Moncrief, JS, Barroso, LA and Wilkins, TD (1997). Positive regulation of Clostridium difficile toxins. Infection and Immunity 65: 11051108.
Moncrief, JS, Zheng, L, Neville, LM and Lyerly, DM (2000). Genetic characterization of toxin A–negative, toxin B–positive Clostridium difficile isolates by PCR. Journal of Clinical Microbiology 38: 30723075.
O'Connor, D, Hynes, P, Cormican, M, Collins, E, Corbett-Feeney, G and Cassidy, M (2001). Evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of Clostridium difficile-associated diarrhea. Journal of Clinical Microbiology 39: 28462849.
Olson, MM, Shanholtzer, CJ, Lee, JT and Gerding, DN Jr (1994). Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982–1991. Infection Control and Hospital Epidemiology 15: 371381.
Post, KW and Songer, JG (2001). Antimicrobial susceptibility of Clostridium difficile isolated from neonatal pigs with enteritis, In: Proceedings, 44th Annual Meeting of the American Association of Veterinary Laboratory Diagnosticians p. 65
Post, KW, Glock, RD, Holtcamp, A, Jost, BH and Glenn Songer, J (2000). Reproduction of Clostridium difficile associated enteritis by experimental inoculation of piglets. In: Proceedings, 43rd Annual Meeting of the American Association of Veterinary Laboratory DiagnosticiansBirmingham AL.
Post, KW, Songer, JG, Jost, BH, Glock, RD and Holtcamp, A (2001). The emergence of Clostridium difficile as a cause of porcine neonatal enteritis. In: Proceedings, 32nd Annual Meeting of the American Association of Swine VeterinariansNashville TN.
Post, KW, Jost, BH and Songer, JG (2002). Evaluation of the Clostridium difficile TOX A/B test for the diagnosis of neonatal swine enteritis. Journal of Veterinary Diagnostic Investigation 14: 258259.
Pothoulakis, C and LaMont, JT (1993). Clostridium difficile colitis and diarrhea. Gastroenterology Clinics of North America 22: 623637.
Poxton, IR, McCoubrey, J and Blair, G (2001). The pathogenicity of Clostridium difficile. Clinical Microbiology and Infection 7: 421427.
Price, AB and Davies, DR (1977). Pseudomembranous colitis. Journal of Clinical Pathology 30: 112.
Riegler, M, Pothoulakis, C and Hamilton, G (1995). Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. Journal of Clinical Investigation 95: 20042011.
Ryan, ET, Butterton, JR, Smith, RN, Carroll, PA, Crean, TI and Calderwood, SB (1997). Protective immunity against Clostridium difficile toxin A induced by oral immunization with a live, attenuated Vibrio cholerae vector strain. Infection and Immunity 65: 29412949.
Salcedo, J, Keates, S and Pothoulakis, C (1997). Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 41: 366370.
Schellenberg, D, Bonington, A, Champion, CM, Lancaster, R, Webb, S and Main, J (1994). Treatment of Clostridium difficile diarrhoea with brewer's yeast. Lancet 343: 171172.
Songer, JG (1996). Clostridial enteric diseases of domestic animals: a review. Clinical Microbiology Reviews 9: 216234.
Songer, JG (2001). A practical approach to clostridial infections. In: Emerging Infections and Molecular Pathogenesis. Annual Meeting of the American College of Veterinary Pathologists, Salt Lake City, UT, December 2–5.
Songer, JG, Post, KW, Larson, DJ, Jost, BH and Glock, RD (2000a). Clostridium difficile as a cause of porcine neonatal enteritis. In: Proceedings, 43rd Annual Meeting of the American Association of Veterinary Laboratory DiagnosticiansBirmingham AL.
Songer, JG, Post, KW, Larson, DJ, Jost, BH and Glock, RD (2000b). Enteric infection of neonatal swine with Clostridium difficile. Swine Health and Production 8: 185189.
Teasley, DG, Gerding, DN and Olson, MM (1983). Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhea and colitis. Lancet 2: 10431046.
Tjellstrom, B, Stenhammar, L, Eriksson, S and Magnusson, KE (1993). Oral immunoglobulin A supplement in treatment of Clostridium difficile enteritis [letter]. Lancet 341: 701702.
Viscidi, R, Laughon, BE and Yolken, R (1983). Serum antibody response to toxins A and B of Clostridium difficile. Journal of Infectious Diseases 148: 93100.
von Eichel-Streiber, C, Boquet, P, Sauerborn, M and Thelestam, M (1996). Large clostridial cytotoxins: a family of glycosyltransferases modifying small GTP-binding proteins. Trends in Microbiology 4: 375382.
Ward, SJ, Douce, G, Dougan, G and Wren, BW (1999a). Local and systemic neutralizing antibody responses induced by intranasal immunization with the nontoxic binding domain of toxin A from Clostridium difficile. Infection and Immunity 67: 51245132.
Ward, SJ, Douce, G, Fingueiredo, D, Dougan, G and Wren, BW (1999b). Immunogenicity of a Salmonella typhimurium aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A. Infection and Immunity 67: 21452152.
Warny, M, Vaerman, JP, Avesani, V and Delmee, M (1994). Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infection and Immunity 62: 384389.
Warny, M, Fatimi, A and Bostwick, EF (1999). Bovine immunoglobulin concentrate– Clostridium difficile retains C. difficile toxin neutralising activity after passage through the human stomach and small intestine. Gut 44: 212217.
Waters, EH, Orr, JP, Clark, EG and Schaufele, CM (1998). Typhlocolitis caused by Clostridium difficile in suckling piglets. Journal of Veterinary Diagnostic Investigation 10: 104108.
Whittier, S, Shapiro, DS and Kelly, WF (1993). Evaluation of four commercially available enzyme immunoassays for laboratory diagnosis of Clostridium difficile-associated diseases. Journal of Clinical Microbiology 31: 28612865.
Wilcox, MH (1996). Cleaning up Clostridium difficile infection. Lancet 348: 767768.
Wilcox, MH, Fawley, WN, Settle, CD and Davidson, A (1998). Recurrence of symptoms in Clostridium difficile infection: relapse or reinfection? Journal of Hospital Infection 38: 93100.
Wren, BW, Russell, RR and Tabagchali, S (1991). Antigenic cross-reactivity and functional inhibition by antibodies to Clostridium difficile toxin A, Streptococcus mutans glucan-binding protein and a synthetic peptide. Infection and Immunity 59: 31513155.
Yaeger, M (2001). Clostridium difficile and other emerging enteric diseases. In: Iowa Swine Disease Conference, Iowa State UniversityAmes, IANovember 9–10, 2001.
Yaeger, M, Funk, N and Hoffman, L (2002). A survey of agents associated with neonatal diarrhea in Iowa swine including Clostridium difficile and porcine reproductive and respiratory syndrome virus. Journal of Veterinary Diagnostic Investigation 14: 281287.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed