What does a positive Clostridioides difficile (C. diff) lab result indicate?

Understanding C. difficile Lab Results

A positive Clostridioides difficile (C. diff) lab result indicates the presence of toxigenic C. difficile in the stool sample, which may cause C. difficile infection (CDI) in symptomatic patients with diarrhea, but requires clinical correlation as it can also represent asymptomatic colonization in patients without significant diarrhea. 1

Types of C. difficile Tests and Their Interpretation

Nucleic Acid Amplification Tests (NAATs)

• Detect genes for toxin production (tcdB)
• Very high sensitivity (95%) and specificity (98%) 1
• Positive likelihood ratio of 46 (patient with C. difficile is 46 times more likely to have a positive result) 1, 2
• Negative likelihood ratio of 0.05 (patient with C. difficile is 20 times less likely to have a negative result) 1, 2
• Cannot distinguish between infection and colonization

Enzyme Immunoassays (EIAs)

• Toxin A/B EIAs: Detect free toxins in stool
• Lower sensitivity (66-73%) but good specificity (92%) 1
• Positive result strongly correlates with active disease

Glutamate Dehydrogenase (GDH) Tests

• Detect C. difficile presence but not toxin production
• High sensitivity but cannot distinguish toxigenic from non-toxigenic strains

Multi-step Algorithms

• GDH/NAAT: Sensitivity 91%, Specificity 99% 1
• GDH/Toxin/NAAT: Sensitivity 89%, Specificity 99% 1

Clinical Interpretation of Results

When a C. diff Test is Positive

1. Confirm clinical symptoms:

   • Patient should have ≥3 unformed stools in 24 hours 1
   • Without diarrhea, a positive result likely represents colonization, not infection

2. Consider the test method:

   • NAAT positive only: May indicate colonization or infection
   • Toxin EIA positive: Strongly suggests active infection
   • Multi-step algorithm positive: Higher positive predictive value for true infection

3. Risk factors to consider:

   • Recent antibiotic exposure
   • Age ≥65 years
   • Hospitalization or healthcare facility exposure
   • Immunocompromised status
   • Previous C. difficile infection

Important Caveats

• Do not repeat testing within 7 days during the same diarrheal episode as this only increases diagnostic yield by approximately 2% 1
• Do not test formed stools as C. difficile testing should only be performed on unformed stool samples 1
• Do not test for cure after treatment as patients may remain positive for weeks after symptoms resolve

Diagnostic Algorithms

Recommended Testing Approach

1. First step: Verify patient has ≥3 unformed stools in 24 hours
2. Second step: Choose one of these testing strategies:
   • NAAT alone (highest sensitivity)
   • Two-step algorithm: GDH screen followed by toxin EIA or NAAT
   • Three-step algorithm: GDH screen, followed by toxin EIA, with NAAT as arbitrator for discordant results

Interpretation of Multi-step Results

• GDH+/Toxin+: Active CDI likely
• GDH+/Toxin-/NAAT+: Possible CDI or colonization
• GDH-: C. difficile unlikely (high negative predictive value)

Clinical Management Based on Results

• Positive test + appropriate symptoms: Treat for CDI with oral vancomycin or fidaxomicin (not metronidazole) 3
• Positive test without significant diarrhea: Do not treat; likely represents colonization
• Negative test with high clinical suspicion: Consider repeat testing only if clinical picture changes significantly

Remember that C. difficile is the most common healthcare-associated infection in the United States 4, and proper interpretation of test results is crucial for appropriate management and prevention of unnecessary treatment.