MULTICENTER EVALUATION OF THE CLOSTRIDIUM-DIFFICILE TOX A B TEST/

Clostridium difficile, the primary cause of nosocomial diarrhea in the United States and many other industrialized countries, is recognized as a major health concern because of its ability to cause severe intes tinal disease leading to complications such as relapses and infections due to vancomycin-resistant enterococci. The disease results from two toxins, toxins A and B, produced by this pathogen. In this study, we evaluated the TOX A/B TEST, a new l-h enzyme immunoassay (EIA) that de tects toxins A and B. We compared the test with the tissue culture ass ay, which is recognized as the ''gold standard'' for C. difficile test ing. Evaluations were per formed in-house at TechLab, Inc. (Blacksburg , Va.) and off-site at four clinical laboratories. Of 1,152 specimens tested, 165 were positive by the TOX A/B TEST and tissue culture and 9 73 were negative by both tests. The sensitivity and specificity were 9 2.2 and 100%, respectively. The positive and negative predictive value s were 100 and 98.6%, respectively, and the correlation of the TOX A/B TEST with tissue culture was 98.8%. When discrepant samples were reso lved by culture, the sensitivity and specificity were 93.2 and 98.9%, respectively, The positive and negative predictive values were 100 and 98.8%, respectively, with a correlation of 99.0%. There were no speci mens that were positive by the TOX A/B TEST and negative by tissue cul ture. Fourteen specimens were negative by the TOX A/B TEST but positiv e by tissue culture. Of these, two were negative by toxigenic culture, five were positive by toxigenic culture, and seven were not available for further testing. There were no indeterminate results, since the t est does not have an indeterminant zone. In a separate study, 102 spec imens that were positive by tissue culture and the TOX A/B TEST were e xamined in toxin A-specific EIAs. Two specimens that presumptively con tained toxin A-negative, toxin B-positive (toxA-/toxB+) isolates were identified. One specimen was from a patient with a clinical history co nsistent with C. difficile infection. Isolates obtained from these spe cimens by selective culture on solid media and in broth tested toxA-/t oxB+ when grown in brain heart infusion dialysis flasks, which stimula te in vitro production of both toxins. Our findings show that the TOX A/B TEST is suitable as a diagnostic aid for Ci difficile disease beca use it correlates well with tissue culture and detects isolates that m ay be missed,vith toxin A-specific EIAs.