What specific blood test is used to diagnose Clostridioides difficile (C. diff)?

C. difficile Is NOT Diagnosed with Blood Tests—Only Stool Testing Is Used

C. difficile infection (CDI) is diagnosed exclusively through stool sample testing, not blood draws. There is no blood test available or recommended for diagnosing C. difficile infection 1, 2.

Why Stool Testing Is Required

• C. difficile causes disease through toxins A and B that are released directly into the intestinal tract, making stool the only appropriate specimen for detecting either the organism, its toxins, or its genetic material 1, 3.
• Blood tests cannot detect C. difficile toxins, the organism itself, or its DNA, as CDI is a localized gastrointestinal infection rather than a bloodstream infection 1.

Correct Diagnostic Approach: Two-Step Stool Testing Algorithm

The recommended diagnostic approach uses a two-step algorithm on unformed stool samples 1, 2:

Step 1: High-Sensitivity Screening

• Screen first with either:
  • GDH (glutamate dehydrogenase) enzyme immunoassay with sensitivity of 90-94% 1, 4, or
  • NAAT/PCR (nucleic acid amplification test) with sensitivity of 91-92% 1, 4
• GDH is produced by all C. difficile strains (both toxigenic and non-toxigenic), making it an excellent screening marker but not diagnostic alone 1.

Step 2: Confirmatory Testing

• For positive screening results, confirm with toxin A/B detection to distinguish active infection from asymptomatic colonization 1, 3.
• Toxin A/B assays have high specificity (97-100%) but lower sensitivity (48-96% depending on the assay) 3.
• This two-step approach achieves optimal performance with 91% sensitivity, 98% specificity, and positive predictive values of 82-85% at endemic prevalence rates 1.

Critical Sample Collection Requirements

• Only test unformed stool samples from symptomatic patients with ≥3 unformed stools in 24 hours 3, 2.
• Testing formed stool or asymptomatic patients leads to false positives by detecting colonization rather than active infection 2.
• For patients with severe CDI complicated by ileus (where stool cannot be obtained), perirectal swabs may provide an acceptable alternative 2.

Common Pitfall to Avoid

• Never use toxin A/B enzyme immunoassay as a standalone test despite its high specificity, as sensitivity is too low (48-66% compared to toxigenic culture), missing nearly half of true CDI cases 1, 3.
• Single-step testing with any method has unacceptably low positive predictive values (28-77%) at endemic prevalence rates of 5-10% 1, 3.