Clostridium difficile testing algorithms: what is practical and feasible?

There has been renewed interest in the laboratory diagnosis of Clostridium difficile infections due in large measure to the increase in both numbers and severity of cases of this disease. For the past two decades, enzyme-immunoassays (EIAs) for the detection of first C. difficile toxin A and then toxins A and B have been the most widely used diagnostic test for diagnosis of C. difficile infections. Recently this diagnostic approach has been called into question by the recognition that a screening test which detects glutamate dehydrogenase, a cell wall antigen of C. difficile, was significantly more sensitive than toxins A and B EIAs making it an effective screening test for C. difficile infection. Although sensitive, GDH lacks specificity and so if this test was utilized, a confirmatory test to differentiate false positives from true positives was needed. Studies to date have used cytotoxin neutralization or toxigenic culture as confirmatory tests but both of these have their limitations. A testing algorithm using rapid immunochromatographic devices for detection of GDH and toxins A and B as screening tests will give an accurate test result in approximately 90% of specimens within one hour when using cytotoxin neutralization as a reference method. For the other 10% of specimens, a third test would be needed in the algorithm. This test could be cytotoxin neutralization, toxigenic culture, or PCR for toxin or toxin operon genes.