Comparison of Detection Methods for the Rapid Identification of Toxigenic Clostridium difficile
ON Kryvenko, LP Samuel, RJ Tibbetts. Henry Ford Hospital, Detroit, MI
Background: Clostridium difficile associated disease (CDAD) is a common nosocomial complication resulting in hospital-associated diarrhea following administration of broad-spectrum antibiotics. In spite of the growing incidence of CDAD the sensitivity of the enzyme immunoassay (EIA), the most commonly used diagnostic test, remains suboptimal. Our goal was to increase sensitivity and specificity while preserving the short turnaround time and relatively low cost of the diagnostic algorithm.
Design: We conducted a prospective study in which we analyzed 294 consecutively submitted specimens for C. diff by EIA, antigen card assay (AA), antigen/toxin combination card assay (ATA), and PCR. Discrepant results were sent out for toxigenic culture, currently the gold standard for C. diff detection.
Results: The prevalence of CDAD in tested population was 9.5%. EIA in our hands had a sensitivity ∼68%, specificity ∼98%, PPV of 76%, and NPV of 96.65%, which is in keeping with reports in the literature. The EIA had a false positive rate of 2.04% (6/294) and false negative of 3.06% (9/294) with resultant patient health risk and related medicolegal and financial issues. AA had a NPV of 100% but specificity of 82.71%. ATA combination had a PPV of 100% and a sensitivity of 64.29%. The PCR had sensitivity of 85.71% and specificity of 96.60%. The PCR testing of all ATA assay antigen positive and toxin negative results (11.22% of tested individuals) identified all cases that were falsely toxin negative. This combination of ATA and PCR achieved sensitivity of 100%, specificity of 98.87%, PPV of 90.32%, and NPV of 100%. The overall cost is 2.75 times higher than that of EIA along which is negligible compared to expenses related to wrong results.
Conclusions: The combination of ATA and PCR is a powerful diagnostic tool for screening and confirmation of CDAD. The antigen component of ATA with a NPV of 100% reliably screens out healthy individuals. The ATA has NPV of 96.38% and PPV of 100% which markedly reduces the number of confirmatory PCR tests. ATA is a rapid manual test performed without sophisticated equipment, it has a random access nature and a set of 30 tests will need 45 minutes to be completed in experienced hands. Addition of confirmatory PCR to antigen/toxin combination in cases of discrepant results allows maintaining NPV at 100% level with very high specificity while having roughly 1% of falsely positive results. The application of this combination of tests is a very cost effective diagnostic tool with dramatic improvement in patient care.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 218, Wednesday Afternoon