Role of Fecal Immunoassay Testing in Diagnosing C. difficile Infection
Fecal immunoassay testing should be used as part of a two-step algorithm for diagnosing Clostridioides difficile infection (CDI), with enzyme immunoassays (EIAs) for glutamate dehydrogenase (GDH) as an initial screening test followed by toxin A/B detection for confirmation. 1
Diagnostic Approach for C. difficile
When to Test
- Test only unformed stool samples from symptomatic patients with ≥3 unformed stools in 24 hours 1
- Consider testing in:
- Patients >2 years of age with diarrhea following antimicrobial use
- Patients with healthcare-associated diarrhea
- Patients with persistent diarrhea without an identified cause 1
Specimen Collection
- Fresh diarrheal stool sample (takes the shape of the container) is the preferred specimen 1
- For patients with suspected severe CDI complicated by ileus who cannot produce stool specimens, perirectal swabs may be used (sensitivity 95.7%, specificity 100%) 1
- A single stool specimen is sufficient; multiple specimens do not increase diagnostic yield 1
Testing Methods and Their Characteristics
Two-Step Algorithm
- First step: GDH EIA (high sensitivity screening test)
- Second step: Toxin A/B EIA (confirmation test)
Test Performance Characteristics
| Test | Sensitivity | Specificity | Advantages | Disadvantages |
|---|---|---|---|---|
| GDH EIA | High | Moderate | Excellent screening test | Cannot differentiate toxigenic strains |
| Toxin A/B EIA | 32-98% | 84-100% | Fast, inexpensive | Variable sensitivity |
| NAATs | 80-100% | 87-99% | High sensitivity, rapid results | May detect colonization, not just infection |
| Toxigenic culture | High | High | Gold standard | Slow, labor-intensive |
Test Interpretation
- Negative first test: Report as negative for CDI 1
- Positive first test + positive confirmatory test: Report as positive for CDI 1
- Positive first test + negative confirmatory test: Cannot differentiate between infection and colonization 1
Common Pitfalls in CDI Diagnosis
Testing formed stool: Only test unformed stool samples, as C. difficile can colonize without causing disease 1
Over-reliance on single tests: No single test is perfect; laboratory results must be interpreted in the context of clinical presentation 1
Confusing colonization with infection: A positive bacterial culture or NAAT without toxin detection may indicate colonization rather than infection 1
Repeat testing during the same episode: A single stool specimen is sufficient; multiple specimens do not increase diagnostic yield 1
Testing for cure: Avoid "test of cure" as patients may remain colonized after successful treatment 1
Clinical Context for Test Interpretation
The diagnosis of C. difficile infection requires both:
- Presence of compatible symptoms (typically diarrhea)
- Laboratory evidence of toxigenic C. difficile or its toxins in stool 1
Treatment Based on Diagnosis
Once CDI is confirmed through appropriate testing, treatment should be initiated:
- First-line treatment: Fidaxomicin 200 mg twice daily for 10 days 1, 2
- Alternative first-line: Vancomycin 125 mg four times daily for 10 days 1, 2
- For non-severe CDI only (if first-line unavailable): Metronidazole 500 mg three times daily by mouth for 10-14 days 1, 2
Recent Developments
Recent studies emphasize the importance of proper diagnostic testing for CDI, with a shift away from metronidazole as first-line therapy 2, 3. The 2024 literature continues to support the two-step algorithm for diagnosis, highlighting that no single test should be used alone 4, 5, 3.
Fecal immunoassay testing remains a cornerstone in the diagnosis of C. difficile infection, providing rapid results when used appropriately as part of a comprehensive diagnostic approach.