Rapid C. difficile Tests
The rapid tests for diagnosing C. difficile infection include enzyme immunoassays (EIAs) for glutamate dehydrogenase (GDH), EIAs for toxins A and B, and nucleic acid amplification tests (NAATs/PCR) that detect toxin genes directly from stool specimens. 1
Primary Rapid Test Categories
Glutamate Dehydrogenase (GDH) Tests
- GDH enzyme immunoassays serve as rapid screening tests with high sensitivity (90-94%) but cannot distinguish between toxigenic and non-toxigenic C. difficile strains 2
- GDH is produced by all C. difficile strains, making it useful for ruling out infection but requiring confirmatory testing when positive 1, 2
- Turnaround time is rapid, typically 1-2 hours 1
Toxin A/B Enzyme Immunoassays (EIAs)
- Well-type EIAs detecting both toxins A and B demonstrate mean sensitivity of 82% and specificity of 97% 2
- Membrane-type EIAs show lower sensitivity of 72% but maintain high specificity of 98% 2
- Commercial examples include TOX A/B QUIK CHEK (sensitivity 95.7%, specificity 100%), ImmunoCard Toxins A&B (sensitivity 91.3%, specificity 100%), and Xpect C. difficile toxin A/B (sensitivity 91.3%, specificity 100%) 3
- Results available within 1.5-4 hours 1, 4
Nucleic Acid Amplification Tests (NAATs)
- Real-time PCR assays detect C. difficile toxin genes with sensitivity of 91-99% and specificity of 87-99% 1, 2
- Commercial NAAT platforms include:
- Xpert C. difficile (sensitivity 99%, specificity >99%) 5
- Simplexa C. difficile Universal Direct (sensitivity 95%, specificity >99%) 5
- Illumigene C. difficile (sensitivity 93%, specificity >99%) 5
- BDmax Cdiff (sensitivity 92%, specificity >99%) 5
- revogene C. difficile assay (sensitivity 97.1%, specificity 98.9%) 6
- Turnaround time ranges from 45 minutes to 2.5 hours depending on platform 5
Critical Limitation: No Single Rapid Test Is Adequate Alone
Never rely on any single rapid test as a standalone diagnostic method because toxin EIAs have unacceptably low sensitivity (48-66% when compared to toxigenic culture), and NAATs cannot distinguish active infection from asymptomatic colonization 2, 4, 7
The Two-Step Algorithm Problem
- At endemic CDI prevalence of 5-10%, toxin A/B assays have positive predictive values of only 28-77%, meaning up to 72% of positive results could be false positives 2, 4
- NAAT alone may detect asymptomatic colonization in up to 7% of hospitalized patients, leading to overdiagnosis and unnecessary treatment 1, 7
Recommended Diagnostic Approach
Use a two-step algorithm: screen first with GDH or NAAT, then confirm positive results with toxin A/B detection 1, 2
Step 1: High-Sensitivity Screening
- Perform either GDH EIA (sensitivity 90-94%) or NAAT (sensitivity 91-99%) 1, 2
- If negative, CDI is effectively ruled out with negative predictive value of 98-99% 2, 4
Step 2: Confirmatory Testing
- For positive screening results, confirm with toxin A/B EIA to distinguish active infection from colonization 1, 2
- This combined approach achieves sensitivity of 91%, specificity of 98%, positive predictive value of 82-85%, and negative predictive value of 98-99% 2
Alternative Algorithm
- Some laboratories use GDH screening followed by toxin EIA, with discordant results (GDH positive/toxin negative) reflexed to NAAT or toxigenic culture 1
- This three-step approach provides results for approximately 92% of samples within 4 hours, with only 8% requiring cell cytotoxicity assay 1
Common Pitfalls to Avoid
- Never test formed stool specimens as this detects colonization rather than infection and leads to false positive diagnoses 7
- Do not use toxin A-only assays as they miss 18-39% of true CDI cases that produce only toxin B 2
- Avoid repeat testing during the same diarrheal episode unless in an epidemic setting, as this increases false positives without improving detection in endemic situations 1
- Do not order testing on asymptomatic patients or use results to determine cure, as up to 7% of hospitalized patients are asymptomatically colonized 1