Test Announcements

LabDx introduces an improved algorithm for Clostridium difficile associated disease diagnosis using the C.DIFF QUIK CHEK COMPLETE™ test which simultaneously detects C. difficile glutamate dehydrogenase (GDH) and both A and B toxins of C. difficile.

Background:
Clostridium difficile is the leading cause of diarrhea in hospitalized patients and the disease is becoming increasingly community acquired. A recent report from the federal Agency for Healthcare Research and Quality shows an increase in the incidence of Clostridium difficile Associated Disease of 200% between 2000 and 2005. This sharp spike follows a 74% increase in the number of cases recorded between 1993 and 2000.

Advantages of antigen tests
Recent studies reveal that toxin-only tests suffer from false negative results with sensitivities reported in the range of 36%-64%. Tests for the common antigen have high sensitivity (98%-100%) as the antigen is produced in large amounts and a high predictive negative value (99%) which mean that patients who test negative can be considered free from C. difficile with 99% certainty. Results are available within 30 minutes for the rapid membrane test.

Announcing changes in testing as an aid in Clostridium difficile diagnosis
When a test for C. difficile (order code CATAB) is selected, all fecal samples will be tested simultaneously for C. difficile glutamate dehydrogenase (common antigen) and both toxins A and B of C. difficile. This new test method will increase sensitivity and will allow a definitive diagnosis in more than 90% of samples with >99% certainty.

Order Code for C. difficile antigen and toxin (CATAB) should be ordered on the LabDx test requisition form.

Results will be recorded as follows

Positive for Clostridium difficile antigen, Positive for Clostridium difficile Toxins A/B
C. difficile is present and producing toxins (prevalence varies with sample population and is usually 5-10%).

Negative for Clostridium difficile antigen, Negative for Clostridium difficile Toxins A/B
C. difficile is not present in the sample.

Positive for Clostridium difficile antigen, Negative for Clostridium difficile Toxins A/B
C. difficile is present, no toxin was detectable.

This last result could be due to infection with a non-toxigenic strain (20 % of C. difficile strains are non-toxigenic) or the level of toxin in the sample was below the level of detection.

If the patient is symptomatic:

1. The American College of Gastroenterology guidelines for the diagnosis and management of CDAD suggest that a positive test for intestinal inflammation such as a test for elevated lactoferrin (LE UKO EZ VUE) is sufficient to warrant therapy in a symptomatic patient.

2. Another sample can be ordered as toxin levels increase during the course of the disease (in untreated patients) and may not have been present in sufficient amounts to be detected in the first specimen.

3. A more sensitive toxin test such as PCR can be performed, when clinically indicated.

References:

1. Wren, et. al., Laboratory Diagnosis of Clostridium difficile infection. An evaluation of tests for faecal toxin, glutamate dehydrogenase, lactoferrin and toxigenic culture in the diagnostic laboratory. British J. Biomedical Science 2009 66(1)
2. Gilligan, P. Is a Two-Step Glutamate Dehydrogenase Antigen Cytotoxicity Neutralization Assay Algorithm Superior to the Premier Toxin A and B Enzyme Immunoassay for Lab Detection of Clostridium difficile? J. Clin. Microbiol. April 2008 p. 1523-1525.
3. Fenner, L et. al., Rapid and Reliable Diagnostic Algorithm for Detection of Clostridium difficile. J. Clin Microbiol Jan 2008 p. 328-330
4. Ticehurst, J., Aird, D., Dam, L., Borek, A., Hargrove, J., Carroll, K.2006
Effective Detection of Toxigenic Clostridium difficile by a Two Step Algorithm Including Tests for Antigen and Cytotoxin. J. Clin. Microbiol. 44:1145-49
5. Snell, H., M. Ramos, S. Longo, M. John and Z. Hussain. 2004. Performance of the TechLab C. DIFF CHEK-60 Enzyme Immunoassay (EIA) in Combination with the C.difficile Tox A/B II EIA Kit, the Triage C.difficile Panel Immunoassay, and a Cytotoxin Assay for Diagnosis of Clostridium difficile-Associated Diarrhea. J. Clin. Microbiol. 42:4863-4865.
6. Barbut, F., V. Lalande, G. Daprey, P. Cohen, N. Merle, and B. Burghoffer. 2000. Usefulness of simultaneous detection of toxin A and glutamate dehydrogenase for the diagnosis of Clostridium difficile- associated diarrhea. Eur. J. Clin. Microbiol. Infect. Dis. 19:481-484.
7. Vanpoucke, H., T. De Baere, G.Claeys, M. Vaneechoutte, and G. Verschraegen. 2000. Evaluation of six commercial assays for the rapid detection of Clostridium difficile toxin and/or antigen in stool specimens. Clin. Microbiol. Infect. 7:55-64
8. Lee, S. D., D. K. Turgeon, C. W. Ko, T. R. Frische and C. M. Surawicz.2003 Clinical Correlation of Toxin and Common Antigen Enzyme Immunoassay Testing in Patients With Clostridium difficile Disease. Am. J. Gastro. 98:1569-1572
9. Zheng, L., C. W. Genheimer, D. M. Lyerly, Z. Hussain, J. Van Broek, M. Delmee. Multicenter Evaluation of a Rapid Test for Detection of Clostridium difficile in Fecal Specimens. Poster C-030, ASM Orlando, 2006.
10. Milburn, S., R. C. Reyes, M. A. John, D. Ayotte, A. Covacich, R. Lannigan, Z. Hussain. Evaluation of C.DIFF QUIK CHEK and Tox A/B QUIK CHEK for Diagnosis of Clostridium difficile-Associated Diarrhea. Poster C-030 ASM Orlando, May 2006.
11. Lyerly, D. M., L. Zheng, C. Genheimer, S. Sigmon, A. Lewis, K. Long, J. Chance. Detection of Clostridium difficile in Fecal Specimens Using a New Rapid Antigen Test, the C.DIFF QUIK CHEK. Poster C-029, ASM Orlando, May 2006.
12. Zheng. L., S.F. Keller, D. M. Lyerly, R. J. Carman, C.W. Gegenheimer, C.A. Gleaves, S. J. Kohlhepp, S. Young, S. Perez, and K. Ye. 2004. Multicenter Evaluation of a New Screening Test That Detects Clostridium difficile in Fecal Specimens. J. Clin. Microbiol. 42:3837-3840