Testing for Clostridioides difficile Colitis
For patients suspected of having C. difficile colitis, the recommended testing approach is a two-step protocol using nucleic acid amplification tests (NAATs) or glutamate dehydrogenase (GDH) assay as the initial screen, followed by toxin A/B detection for positive initial screens. 1, 2
Patient Selection for Testing
Test only unformed stool samples (liquid or semi-formed stools)
Testing should be performed on patients with:
Do not test:
- Formed stools
- Asymptomatic patients
- Children under 2 years (high asymptomatic colonization rates)
- Patients who have received laxatives in the previous 48 hours
Recommended Testing Algorithms
Option 1: Two-Step Algorithm (Preferred)
- First step: NAAT (detecting toxin B gene) or GDH assay
- Second step: For positive samples, confirm with toxin A/B enzyme immunoassay (EIA)
Option 2: NAAT-Only Testing
NAAT-only testing is also recommended as a best practice for detection of the C. difficile toxin gene, with high sensitivity (80-100%) and specificity (87-99%) 2, 1
Option 3: GDH/NAAT Algorithm
This algorithm is recommended for detection of C. difficile organism/toxin gene with high diagnostic accuracy (LR+ 113.5, LR- 0.09) 2
Option 4: GDH/Toxin/NAAT Algorithm
This three-step algorithm is recommended for detection of C. difficile organism, toxin, or toxin gene with moderate strength of evidence (LR+ 155.8, LR- 0.11) 2
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 | May detect colonization, not infection |
| Toxigenic culture | High | High | Gold standard | Slow, labor-intensive |
Repeat Testing Considerations
- Repeated testing using NAAT within 7 days of a negative result has minimal additional diagnostic yield (only 3% conversion from negative to positive) 2
- Routine repeat testing during the same episode is not recommended in endemic settings 2
- Consider repeat testing only in epidemic situations or with high clinical suspicion despite negative initial testing 2
Additional Diagnostic Approaches
- Imaging: CT scan may show colonic wall thickening, "accordion sign," or "double-halo sign" (sensitivity 52%, specificity 93%) 2
- Ultrasound: May be useful in critically ill patients who cannot be transported for CT scan (shows thickened colonic wall with heterogeneous echogenicity) 2
- Endoscopy: Flexible sigmoidoscopy may be helpful when there is high clinical suspicion but negative stool tests; use sparingly due to perforation risk in fulminant colitis 2
Treatment Initiation
- Begin empiric therapy for suspected severe CDI while awaiting test results if strong clinical suspicion exists 2
- Discontinue inciting antibiotics if possible 2, 1
- For confirmed CDI, select treatment based on severity:
Common Pitfalls to Avoid
- Testing formed stools (leads to detection of asymptomatic carriers)
- Repeat testing during the same episode (low yield, waste of resources)
- "Test of cure" after treatment completion (not recommended)
- Relying solely on toxin EIA without NAAT or GDH (may miss cases due to lower sensitivity)
- Treating patients with positive tests but no diarrhea (asymptomatic colonization)
- Delaying empiric treatment in severely ill patients while awaiting test results
The two-step testing approach balances sensitivity and specificity while minimizing detection of asymptomatic carriers, leading to more appropriate treatment decisions and improved patient outcomes.