Medical Microbiology and Immunology

, Volume 170, Issue 1, pp 27–35

Occurrence of toxin-producingClostridium difficile in antibiotic-associated diarrhea in Sweden

  • B. Aronsson
  • R. Möllby
  • C. E. Nord


From 1324 patients with antibiotic-associated diarrhea (AAD) 1643 stool samples were analyzed by a cell test forClostridium difficile toxin in stool filtrates and cultivation for occurrence ofC. difficile strains. In patients with no detectable toxin in their stool strains ofC. difficile were isolated in 2.2% where as when toxin was detectable, the isolation rate varied from 17% to 36%.

Furthermore, there was a correlation between toxin titre in stool filtrate and production of cytotoxinin vitro by the correspondingC. difficile strains. Five clostridial strains, not belonging to the speciesC. difficile, were found to produce typical cytotoxinin vitro. However, five strains identified asC. difficile by biochemical reactions and gas liquid chromatography, did not produce an extracellular cytotoxin. The antibiotic susceptibility patterns of theClostridium strains were investigated. No correlation was recognized between antibiotic resistance of isolatedClostridium strains and the AAD-inducing antibiotic penicillins and linco/clindamycin. Neither did cases of relapse of diarrheal disease after vancomycin treatment harbourC. difficile strains with increased resistance to vancomycin. It is concluded that the pathogenesis of antibiotic-associated enterocolitis is more complex than a mere intestinal overgrowth of resistant strains ofC. difficile.


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  1. Bartlett JG (1979) Antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1: 530–539PubMedGoogle Scholar
  2. Bartlett JG (1980) In: Kallings LO, Möllby R, Nord CE (eds) Antibiotic-associated colitis andClostridium difficile. Scand J Inf Dis Suppl 22:47Google Scholar
  3. Bolton RP, Sheriff RJ, Read AE (1980)C. difficile associated diarrhoea. A role in inflammatory bowel disease? Lancet 1:383–384CrossRefPubMedGoogle Scholar
  4. Burdon DW, Brown JD, Youngs DJ, Arabi Y, Shinagawa N, Alexander-Williams J, Keighley MRB (1979) Antibiotic susceptibility ofC. difficile. J Antimicrob Chemother 5:307–310PubMedGoogle Scholar
  5. Chang TW, Gorbach SL, Bartlett JB (1978) Neutralization ofClostridium difficile toxin byClostridium sordelli antitoxins. Infect Immun 22:418–422PubMedGoogle Scholar
  6. Dornbusch K, Nord CE, DahlbÄck A (1975) Antibiotic susceptibility ofClostridium species isolated from human infections. Scand J Inf Dis 7:127–134Google Scholar
  7. Dzink J, Bartlett JG (1980)In vitro susceptibility ofC. difficile isolates from patients with antibiotic-associated diarrhea or colitis. Antimicrob Agents Chemother 17: 695–698PubMedGoogle Scholar
  8. Ellner PD (1956) A medium promoting rapid quantitative sporulation inClostridium perfringens. J Bacteriol 71:495–496PubMedGoogle Scholar
  9. Eriksson S (1980) Antibiotic induced pseudomembranous colitis. LÄkartidningen 30/31: 2630–2631Google Scholar
  10. Falsen E, Kaijser B, Nehls L, Nygren B, Svedhem å (1980)C. difficile in relation to enteric bacterial pathogens. J Clin Microbiol 12:297–300PubMedGoogle Scholar
  11. Fekety R, Silva J, Toshniwal R, Allo M, Armstrong J, Browne R, Ebright J, Riwkin G (1979) Antibiotic-associated colitis: Effect of antibiotics onC. difficile and the disease in hamster. Rev Inf Dis 1:386–396Google Scholar
  12. Fekety R, Kim KH, Brown D, Batts DH, Cudmore MA, Silva J (1980) Epidemiology of antibiotic associated colitis: Isolation ofClostridium difficile from hospital environment. Int Conf on Nosocomial Infections, Atlanta Aug 5–8Google Scholar
  13. George RH, Symonds JM, Dimock F, Brown JD, Arabi Y, Shinagawa N, Keighley MRB, Alexander-Williams J, Burdon DW (1978) Identification ofC. difficile as a cause of pseudomembranous colitis. Brit Med J 1:695PubMedGoogle Scholar
  14. George WL, Sutter VL, Finegold SM (1977) Antimicrobial agent-induced diarrhoea — a bacterial disease. J Inf Dis 136:822–828Google Scholar
  15. George WL, Sutter VL, Finegold SM (1978) Toxigenicity and antimicrobial susceptibility ofC. difficile — a cause of antimicrobial agent-associated colitis. Curr Microbiol 1:55–58Google Scholar
  16. George WL, Sutter VL, Citron D, Finegold SM (1979) Selective and differential medium for isolaton ofC. difficile. J Clin Microbiol 9:214–219PubMedGoogle Scholar
  17. George WL, Kirby BD, Sutter VL, Finegold SM (1979) Antimicrobial susceptibility ofClostridium difficile. In: Schlessinger D (ed) Microbiology — 1979. American Society for Microbiology, Washington, USAGoogle Scholar
  18. Greenfield C, Szawathowski M, Noone P, Burroughs A, Bass N, Pounder R (1981) Is pseudomembranous colitis infectious? Lancet 1:371–372CrossRefPubMedGoogle Scholar
  19. Hall IC, O'Toole E (1935) Intestinal flora in new-born infants with a description of a new pathogenic anaerobe,Bacillus difficilis. Am J Dis Child 49:390–402Google Scholar
  20. Holdeman V, Cato EP, Moore WEC (1977) Anaerobe Laboratory Manual 4th ed. Virginia Polytechnic Institute and State University, BlacksburgGoogle Scholar
  21. Holst E, Helin I, Mårdh P-A (1981) Recovery ofClostridium difficile from children. Scand J Infect Dis 13:41–45PubMedGoogle Scholar
  22. Ionesco H (1980) Transfer de la résistance à la tétracycline chezClostridium difficile. Ann Microbiol (Inst Pasteur) 131 A:171–179Google Scholar
  23. Howard JM, Sullivan SN, Troster M (1980) Spontaneous pseudomembranous colitis. Brit Med J 281:356Google Scholar
  24. Kabins SA, Spira TJ (1975) Outbreak of clindamycin-associated colitis (letter). Ann Intern Med 83:830–831PubMedGoogle Scholar
  25. Keighley MRB, Burdon DW, Mogg GAG, George RH, Alexander-Williams J, Thompson H (1979) Pseudomembranous colitis (letter). Lancet 1:559–560CrossRefGoogle Scholar
  26. Knoop FC (1979) Clindamycin-associated enterocolitis in guinea pigs: evidence for a bacterial toxin. Infect immun 23:31–33PubMedGoogle Scholar
  27. LaMont TJ, Sonnenblick EB, Rothman S (1979) Role of clostridial toxin in the pathogenesis of clindamycin colitis in rabbits. Gastroenterology 76:356–361PubMedGoogle Scholar
  28. Lamont JT, Trnka YM (1980) Therapeutic implications ofC. difficile toxin during relapse of chronic inflammatory bowel disease. Lancet 1:381–383CrossRefPubMedGoogle Scholar
  29. Larson HE, Price AB, Honour P, Borrelio SP (1978)Clostridium difficile and the etiology of pseudomembranous colitis. Lancet 1:1063–1066CrossRefPubMedGoogle Scholar
  30. Larson HE (1979) Pseudomembranous colitis is an infection. J Infect 1:221–226CrossRefGoogle Scholar
  31. Larson HE, Price AB, Borrelio SP (1980) Epidemiology of experimental enterocolitis due toClostridium difficile. J Inf Dis 142:408–413Google Scholar
  32. Möllby R, Nord CE, Aronsson B (1980) Diagnosis ofC. difficile associated enterocolitis in Sweden. Laboratory and epidemiological aspects. Scand J Inf Dis Suppl 22:30–36Google Scholar
  33. Nord CE, Heimdahl A (1979) Effect of phenoximethylpenicillin and clindamycin on the oral, throat and faecal microflora of man. Scand J Inf Dis 11:233–242Google Scholar
  34. Peikin SR, Galdibini J, Bartlett JG (1980) Role ofC. difficile in a case of non-antibiotic -associated pseudomembranous colitis. Gastroenterology 79:948–951PubMedGoogle Scholar
  35. Rampling A, Everett WG, Sills OA (1980)Clostridium difficile and chronic inflammatory bowel disease. Lancet 1:714–715 (1980)Google Scholar
  36. Rehg JE (1980) Cecal toxin(s) from guinea pigs with clindamycin-associated colitis, neutralized by clostridium sordellii antitoxin. Infect Immun 27:387–390PubMedGoogle Scholar
  37. Scott AJ, Nicholson GI, Kerr A (1973) Lincomycin as a cause of pseudomembranous colitis. Lancet 1:1232–1234CrossRefPubMedGoogle Scholar
  38. Shuttleworth R, Taylor M, Jones DM (1980) Antimicrobial susceptibilities ofClostridium difficile. J Clin Path 33:1002–1005PubMedGoogle Scholar
  39. Thelestam M, Brönnegård M (1980) Interaction of cytopathogenic toxin fromClostridium difficile with cells in tissue culture. Scand J Inf Dis Suppl 22:16–29Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • B. Aronsson
    • 1
    • 2
  • R. Möllby
    • 1
    • 2
  • C. E. Nord
    • 1
    • 2
  1. 1.Department of BacteriologyNational Bacteriological LaboratoryStockholm
  2. 2.Department of Infectious Diseases, Karolinska InstituteRoslagstull HospitalStockholmSweden

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