Skip to main content

Advertisement

Log in

Superiority of the DNA Amplification Assay for the Diagnosis of C. difficile Infection: A Clinical Comparison of Fecal Tests

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Clostridium difficile infection (CDI) is a major infectious concern, accounting for substantial morbidity and resource utilization. Advances in microbiological and molecular techniques have resulted in an increasing number of testing options for CDI. A glutamate dehydrogenase (GDH) enzyme immunoassay (EIA) and a DNA amplification (DNA-A) test for the diagnosis of CDI have recently become commercially available.

Aims

The aim of this prospective study was to compare the test performance characteristics of the traditional diagnostic modality for CDI diagnosis, the toxin A/B (TOX) EIA, with those of the GDH EIA and DNA-A test, utilizing enriched toxigenic culture (TGC) as the gold standard. Clinical variables predictive of CDI were also studied.

Methods

Participants fulfilled one or more criteria placing them at increased risk for CDI. Each stool sample was tested by each of the methods mentioned above. Clinical data parameters were collected via a 12-month review of the electronic medical record prior to the index date of the first stool test.

Results

A total of 272 stool samples from 144 admissions of 139 patients were evaluated for CDI. The sensitivity and positive predictive value (PPV) of the TOX EIA were 86.1 and 58.4 %, respectively, whereas the sensitivity and PPV of the GDH EIA and DNA-A test were 100 %. 1.8 % of the GDH tests yielded inconclusive results. Using TGC as the gold standard, nosocomial exposure with emphasis on nursing home residence, history of previous CDI, and female gender were predictive of CDI.

Conclusions

Test performance characteristics of the DNA-A test and GDH EIA were superior to those of the traditional TOX EIA. The GDH test is limited by inconclusive test results and requires a multi-step diagnostic algorithm. Therefore, the DNA-A test should be implemented as the diagnostic method of choice for CDI. CDI clinical predictors are important for diagnostic decision-making.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile related hospitalizations and case-fatality rate, United States 2000–2005. Emerg Infect Dis. 2008;14:929–931.

    Article  PubMed  Google Scholar 

  2. Kyne L, Hamel MB, Plavaram R, et al. Healthcare costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis. 2002;34:346–353.

    Article  PubMed  Google Scholar 

  3. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors, and management. Nat Rev Gastroenterol Hepatol. 2011;8:17–26.

    Google Scholar 

  4. U.S. Department of Health and Human Services. HCUPnet [online]. Available at: http://hcupnet.ahrq.gov/. Accessed 2010.

  5. Dubberke ER, Wertheimer AI. Review of current literature on the economic burden of Clostridium difficile and C. difficile infection. Infect Control Hosp Epidemiol. 2009;30:57–66.

    Article  PubMed  Google Scholar 

  6. Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhea, and colitis. World J Gastroenterol. 2009;15:1554–1580.

    Google Scholar 

  7. Carroll KC, Bartlett JG. Biology of Clostridium difficile: implications for epidemiology and diagnosis. Ann Rev Microbiol. 2011;65:501–521.

    Google Scholar 

  8. Rupnik M. Heterogeneity of large clostridial toxins: importance of Clostridium difficile toxinotypes. FEMS Microbiol Rev. 2008;32:541–555.

    Article  PubMed  CAS  Google Scholar 

  9. Doing KM, Hintz MS, Keefe C, et al. Reevaluation of the Premier Clostridium difficile toxin A and B immunoassay with comparison to glutamate dehydrogenase common antigen testing evaluation Bartels cytotoxin and ProdeseProGastro Cd polymerase chain reaction as confirmatory procedures. Diagn Microbiol Infect Dis. 2010;66:129–134.

    Article  PubMed  CAS  Google Scholar 

  10. Larson AM, Fung AM, Fang FC. Evaluation of the tcdB real-time PCR in a three-step diagnostic algorithm for detection of toxigenic Clostridium difficile. J Clin Microbiol. 2010;48:124–130.

    Article  PubMed  CAS  Google Scholar 

  11. Kvach EJ, Ferguson D, Riska PF, et al. Comparison of BD GeneOhmCdiff real-time PCR assay with a two-step algorithm and a toxin A/B enzyme-linked immunosorbent assay for diagnosis of toxigenic Clostridium difficile infection. J Clin Microbiol. 2010;48:109–114.

    Article  PubMed  CAS  Google Scholar 

  12. Peterson LR, Manson RU, Paule SM, et al. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis. 2007;45:1152–1160.

    Article  PubMed  CAS  Google Scholar 

  13. Stamper PD, Alcabasa R, Aird D, et al. Comparison of a commercial real-time PCR assay for tcdB detection to a cell culture cytotoxicity assay and toxigenic culture for direct detection of toxin-producing Clostridium difficile in clinical samples. J Clin Microbiol. 2009;47:373–378.

    Article  PubMed  CAS  Google Scholar 

  14. Stamper PD, Babiker W, Alcabasa R, et al. Evaluation of a new commercial TaqMan PCR assay for direct detection of the Clostridium difficile toxin B gene in clinical stool specimens. J Clin Microbiol. 2009;47:3846–3850.

    Article  PubMed  CAS  Google Scholar 

  15. Sloan LM, Duresko BJ, Gustafson DR, et al. Comparison of a real-time PCR for detection of the tcdC gene with four toxin immunoassays and culture in diagnosis of Clostridium difficile infection. J Clin Microbiol. 2008;46:1996–2001.

    Article  PubMed  CAS  Google Scholar 

  16. Barbut F, Braun M, Burghoffer B, et al. Rapid detection of toxigenic strains of Clostridium difficile in diarrheal stools by real-time PCR. J Clin Microbiol. 2009;47:1276–1277.

    Article  PubMed  CAS  Google Scholar 

  17. Eastwood K, Else P, Charlett A, et al. Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J Clin Microbiol. 2009;47:3211–3217.

    Article  PubMed  Google Scholar 

  18. Novak-Weekley SM, Marlowe EM, Miller JM, et al. Clostridium difficile testing in the clinical laboratory by use of multiple testing algorithms. J Clin Microbiol. 2010;48:889–893.

    Article  PubMed  Google Scholar 

  19. Meridian Bioscience. Meridian illumigene assay package insert and product information. Available at: http://www.meridianbioscience.com/diagnostic-products/c-difficile/illumigene-molecular-diagnostic-system/illumigene-c-difficile. 2011. Accessed 19 Oct 2011.

  20. Currie B. Real-time PCR testing for CDI improves outcomes and reduces costs. MLO Med Lab Obs. 2009;41:18–20.

    PubMed  Google Scholar 

  21. Mellow M, Kanatzar A, Brandt L, et al. Long term follow-up of colonoscopic fecal microbiota transplant (FMT) for recurrent C. difficile infection (RCDI). Podium Presentation at American College of Gastroenterology 2011 National Meeting. Washington, DC.

  22. Loo VG, Bourgault A, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Eng J Med. 2011;365:1693–1703.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Funding for laboratory testing provided by Mount Sinai Medical Center, Miami Beach, FL. No other funding sources identified.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jodie A. Barkin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barkin, J.A., Nandi, N., Miller, N. et al. Superiority of the DNA Amplification Assay for the Diagnosis of C. difficile Infection: A Clinical Comparison of Fecal Tests. Dig Dis Sci 57, 2592–2599 (2012). https://doi.org/10.1007/s10620-012-2200-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2200-x

Keywords

Navigation