Search tips
Search criteria 


Logo of jcmPermissionsJournals.ASM.orgJournalJCM ArticleJournal InfoAuthorsReviewers
J Clin Microbiol. 1993 April; 31(4): 963–967.
PMCID: PMC263594

Comparison of three enzyme immunoassays, a cytotoxicity assay, and toxigenic culture for diagnosis of Clostridium difficile-associated diarrhea.


Enzyme immunoassays (EIAs) based on monoclonal antibodies for the detection of Clostridium difficile toxins have recently been developed for clinical use. The aim of this study was to compare three commercially available EIAs, two for toxin A (Premier C. difficile Toxin A; Meridian, Osi, Elancourt, France; and Vidas C. difficile Toxin A; bioMérieux, Marcy l'Etoile, France) and one for toxins A and B (Cytoclone A + B EIA; Cambridge Biotech Corp., Codiapharm, Evian, France), with a cytotoxicity assay and toxigenic culture for the diagnosis of C. difficile-associated diarrhea (CDAD). The study was performed with 285 fresh stools from 285 patients with suspected CDAD. In case of disagreement, the tests were repeated on a frozen aliquot of the same stool sample, and the patient's chart was reviewed. CDAD diagnosis was established in 55 cases (incidence, 19.3%). The sensitivities and specificities of the methods were, respectively, 92.7 and 100% for the cytotoxicity assay, 96.4 and 99.1% for toxigenic culture, 75.5 and 97.8% for Cytoclone, 65.4 and 99.6% for Premier, and 65.4 and 100% for Vidas. The results were uninterpretable in 3.2% of cases with Cytoclone, 0.3% with Premier, and 2.5% with Vidas. We conclude that the cytotoxicity assay and toxigenic culture remain the best methods for the diagnosis of CDAD even though they lack standardization and require 48 to 96 h to obtain the result. Despite their rapidity and simplicity, EIAs are not sensitive enough to be relied on as the sole laboratory test.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aronsson B, Granström M, Möllby R, Nord CE. Enzyme immunoassay for detection of Clostridium difficile toxins A and B in patients with antibiotic-associated diarrhoea and colitis. Eur J Clin Microbiol. 1985 Apr;4(2):102–107. [PubMed]
  • Barbut F, Caburet F, Petit JC. Evaluation d'un test immunoenzymatique (Elisa) détectant la toxine A de Clostridium difficile dans des échantillons de selles. Ann Biol Clin (Paris) 1992;50(1):31–36. [PubMed]
  • Bartlett JG, Moon N, Chang TW, Taylor N, Onderdonk AB. Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978 Nov;75(5):778–782. [PubMed]
  • Bate G. Comparison of Minitek Anaerobe II, API An-Ident, and RapID ANA systems for identification of Clostridium difficile. Am J Clin Pathol. 1986 Jun;85(6):716–718. [PubMed]
  • Bowman RA, Riley TV. Laboratory diagnosis of Clostridium difficile-associated diarrhoea. Eur J Clin Microbiol Infect Dis. 1988 Aug;7(4):476–484. [PubMed]
  • Chang TW, Lauermann M, Bartlett JG. Cytotoxicity assay in antibiotic-associated colitis. J Infect Dis. 1979 Nov;140(5):765–770. [PubMed]
  • DiPersio JR, Varga FJ, Conwell DL, Kraft JA, Kozak KJ, Willis DH. Development of a rapid enzyme immunoassay for Clostridium difficile toxin A and its use in the diagnosis of C. difficile-associated disease. J Clin Microbiol. 1991 Dec;29(12):2724–2730. [PMC free article] [PubMed]
  • Doern GV, Coughlin RT, Wu L. Laboratory diagnosis of Clostridium difficile-associated gastrointestinal disease: comparison of a monoclonal antibody enzyme immunoassay for toxins A and B with a monoclonal antibody enzyme immunoassay for toxin A only and two cytotoxicity assays. J Clin Microbiol. 1992 Aug;30(8):2042–2046. [PMC free article] [PubMed]
  • George WL, Sutter VL, Citron D, Finegold SM. Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol. 1979 Feb;9(2):214–219. [PMC free article] [PubMed]
  • Gerding DN, Olson MM, Peterson LR, Teasley DG, Gebhard RL, Schwartz ML, Lee JT., Jr Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study. Arch Intern Med. 1986 Jan;146(1):95–100. [PubMed]
  • Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile colonisation and disease. Lancet. 1990 Jul 14;336(8707):97–100. [PubMed]
  • Kelly MT, Champagne SG, Sherlock CH, Noble MA, Freeman HJ, Smith JA. Commercial latex agglutination test for detection of Clostridium difficile-associated diarrhea. J Clin Microbiol. 1987 Jul;25(7):1244–1247. [PMC free article] [PubMed]
  • Lyerly DM, Barroso LA, Wilkins TD. Identification of the latex test-reactive protein of Clostridium difficile as glutamate dehydrogenase. J Clin Microbiol. 1991 Nov;29(11):2639–2642. [PMC free article] [PubMed]
  • Lyerly DM, Krivan HC, Wilkins TD. Clostridium difficile: its disease and toxins. Clin Microbiol Rev. 1988 Jan;1(1):1–18. [PMC free article] [PubMed]
  • Lyerly DM, Phelps CJ, Wilkins TD. Monoclonal and specific polyclonal antibodies for immunoassay of Clostridium difficile toxin A. J Clin Microbiol. 1985 Jan;21(1):12–14. [PMC free article] [PubMed]
  • Lyerly DM, Sullivan NM, Wilkins TD. Enzyme-linked immunosorbent assay for Clostridium difficile toxin A. J Clin Microbiol. 1983 Jan;17(1):72–78. [PMC free article] [PubMed]
  • Lyerly DM, Wilkins TD. Commercial latex test for Clostridium difficile toxin A does not detect toxin A. J Clin Microbiol. 1986 Mar;23(3):622–623. [PMC free article] [PubMed]
  • Maniar AC, Williams TW, Hammond GW. Detection of Clostridium difficile toxin in various tissue culture monolayers. J Clin Microbiol. 1987 Oct;25(10):1999–2000. [PMC free article] [PubMed]
  • McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. 1989 Jan 26;320(4):204–210. [PubMed]
  • Mulligan ME. Epidemiology of Clostridium difficile-induced intestinal disease. Rev Infect Dis. 1984 Mar-Apr;6 (Suppl 1):S222–S228. [PubMed]
  • Peterson LR, Olson MM, Shanholtzer CJ, Gerding DN. Results of a prospective, 18-month clinical evaluation of culture, cytotoxin testing, and culturette brand (CDT) latex testing in the diagnosis of Clostridium difficile-associated diarrhea. Diagn Microbiol Infect Dis. 1988 Jun;10(2):85–91. [PubMed]
  • Poxton IR, Byrne MD. Detection of Clostridium difficile toxin by counterimmunoelectrophoresis: a note of caution. J Clin Microbiol. 1981 Sep;14(3):349–349. [PMC free article] [PubMed]
  • Shanholtzer CJ, Willard KE, Holter JJ, Olson MM, Gerding DN, Peterson LR. Comparison of the VIDAS Clostridium difficile toxin A immunoassay with C. difficile culture and cytotoxin and latex tests. J Clin Microbiol. 1992 Jul;30(7):1837–1840. [PMC free article] [PubMed]
  • Tichota-Lee J, Jaqua-Stewart MJ, Benfield D, Simmons JL, Jaqua RA. Effect of age on the sensitivity of cell cultures to Clostridium difficile toxin. Diagn Microbiol Infect Dis. 1987 Dec;8(4):203–214. [PubMed]
  • Varki NM, Aquino TI. Isolation of Clostridium difficile from hospitalized patients without antibiotic-associated diarrhea or colitis. J Clin Microbiol. 1982 Oct;16(4):659–662. [PMC free article] [PubMed]
  • Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology. 1981 Jul;81(1):5–9. [PubMed]
  • Walker RC, Ruane PJ, Rosenblatt JE, Lyerly DM, Gleaves CA, Smith TF, Pierce PF, Jr, Wilkins TD. Comparison of culture, cytotoxicity assays, and enzyme-linked immunosorbent assay for toxin A and toxin B in the diagnosis of Clostridium difficile-related enteric disease. Diagn Microbiol Infect Dis. 1986 May;5(1):61–69. [PubMed]
  • Wilkins TD. Role of Clostridium difficile toxins in disease. Gastroenterology. 1987 Aug;93(2):389–391. [PubMed]
  • Wilson KH, Kennedy MJ, Fekety FR. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile. J Clin Microbiol. 1982 Mar;15(3):443–446. [PMC free article] [PubMed]
  • Woods GL, Iwen PC. Comparison of a dot immunobinding assay, latex agglutination, and cytotoxin assay for laboratory diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol. 1990 May;28(5):855–857. [PMC free article] [PubMed]
  • Wu TC, Fung JC. Evaluation of the usefulness of counterimmunoelectrophoresis for diagnosis of Clostridium difficile-associated colitis in clinical specimens. J Clin Microbiol. 1983 Apr;17(4):610–613. [PMC free article] [PubMed]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)