Clostridium difficile is the major cause of nosocomial diarrhoea and is associated with significant morbidity and mortality. The diarrhoea is classically bloody, which can be a useful indicator of infection, but has limitations in that many other causes of diarrhoea can produce bloody stools and many cases of C. difficile gastroenteritis are not associated with bloody stools. The major indicators of C. difficile testing is recent or current antibiotic use, or a nosocomial setting.
C. difficile usually produces two toxins, toxin A which is an enterotoxin and toxin B which is a cytotoxin and both appear to be involved in disease. Non toxigenic strains are common and are not associated with disease, but are an important consideration for laboratory testing protocols. Strains that are toxin A negative, but toxin B positive have been reported and cause disease that is essentially the same as strains with both toxins, but toxin A positive, toxin B negative strains have not been reported.
Cytotoxin assay: This test involves the use of cell culture to detect the presence of cytotoxin in faecal specimens. It is a relatively slow test that is technically demanding and required ongoing maintenance of the cells even when tests are not being done. It is a very sensitive and specific test, and is considered the "Gold Standard".
Culture: C. difficile can be cultured using selective and differential media and then identified reliably using relatively simple phenotypic tests or even a latex agglutination. The problem with this approach, is that it is slow (48-72 hrs) and that it does not differentiate between toxin producing (significant) and non toxin producing (not significant) isolates.
GDH: Stools can be screened for C. difficile associated Glutamate Dehydrogenase (GDH) antigen, either by EIA or by latex agglutination. This enzyme is not specific for toxin producing C. difficile and can also be produced by other clostridia: so the test is not specific. As a test it is probably quite sensitive, and a negative result is reasonable grounds to exclude C. difficile as a cause of diarrhoea.
Toxin EIA: EIA techniques to detect either or both of toxin A and toxin B. It is best to use tests that detect both toxin A and B because of the presence of occasional strains that are toxin A negative. These tests have the advantage of being easily automated, but all suffer from relatively low sensitivity in comparison to either cytotoxin or culture with toxin testing. The tests are reasonably specific and a positive test in a patient with consistent clinical findings would be diagniostic.
For More information: