Laboratory diagnosis of Clostridium difficile infection (CDI) in a patient on antibiotics with pseudomembranous colitis should include detection of toxins. What is the GOLD STANDARD diagnostic method and which toxins should be specifically detected?
- A Stool culture on CCFA agar — definitive gold standard
- B EIA detecting only toxin A (enterotoxin)
- C Glutamate dehydrogenase (GDH) antigen detection — confirmatory test
- D Cell cytotoxicity neutralization assay (CCNA) detecting toxin B (cytotoxin) ✓
Explanation
The cell cytotoxicity neutralization assay (CCNA) is the historical gold standard for CDI diagnosis, detecting the cytopathic effect of toxin B (cytotoxin) neutralizable by antitoxin on cell cultures — high sensitivity and specificity. Toxin B is 10× more potent than toxin A and is the primary mediator of colitis. EIA for toxin A alone misses toxin A-negative/toxin B-positive strains. GDH EIA is a sensitive screening test (not confirmatory) that detects all C. difficile including non-toxigenic strains. Current guidelines recommend NAAT (PCR) for genes tcdA/tcdB in combination with toxin EIA.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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