What is the treatment approach for a patient with a Clostridioides difficile (C. diff) Glutamate Dehydrogenase (GDH) positive result but negative for other antigens?

Treatment Approach for C. difficile GDH Positive and Other Antigens Negative

No antibiotic treatment is indicated for patients with C. difficile GDH positive but toxin negative results, as this represents colonization rather than active infection in the absence of symptoms. 1

Understanding the Test Results

GDH (glutamate dehydrogenase) is an enzyme produced by both toxigenic and non-toxigenic strains of C. difficile. When a patient tests positive for GDH but negative for toxins, this indicates one of three possibilities:

1. Colonization with non-toxigenic C. difficile (not causing disease)
2. Colonization with toxigenic C. difficile that is not actively producing toxins
3. Possible false negative toxin result

Diagnostic Interpretation

The diagnosis of C. difficile infection (CDI) requires:

• Presence of diarrhea (≥3 unformed stools in 24 hours)
• Positive stool test for toxigenic C. difficile or its toxins 1

GDH testing has excellent sensitivity (90-100%) but limited specificity (81-89%) since it detects both toxigenic and non-toxigenic strains 2, 3, 4. This is why GDH is typically used as a screening test in a multi-step algorithm.

Management Algorithm

1. For GDH positive/toxin negative patients WITHOUT diarrhea:

   • No treatment required
   • Patient has colonization, not infection 1
   • Avoid unnecessary antibiotic exposure

2. For GDH positive/toxin negative patients WITH diarrhea:

   • Consider nucleic acid amplification test (NAAT/PCR) for toxin genes if available 1
   • If PCR positive + symptoms: treat as CDI
   • If PCR negative or unavailable: evaluate for alternative causes of diarrhea

3. For patients with severe symptoms and high clinical suspicion despite negative toxin:

   • Consider empiric therapy while awaiting additional test results 1
   • Consider endoscopy if high clinical suspicion persists 1

Important Considerations

• "Test of cure" is not recommended after CDI treatment 1
• Up to 56% of patients may asymptomatically shed C. difficile spores for up to six weeks after successful treatment 1
• Repeat testing during the same episode is not recommended in endemic situations 1

Treatment Options (if CDI is confirmed)

If additional testing confirms CDI or clinical suspicion remains very high:

• Mild-moderate CDI: Oral metronidazole 500mg three times daily for 10 days 1
• Severe CDI: Oral vancomycin 125mg four times daily for 10-14 days 1
• Recurrent CDI: Consider fidaxomicin 200mg twice daily for 10 days 5

Common Pitfalls to Avoid

1. Treating asymptomatic carriers (GDH positive/toxin negative without diarrhea)
2. Failing to consider alternative causes of diarrhea in GDH positive/toxin negative patients
3. Overreliance on laboratory tests without clinical correlation
4. Performing "test of cure" after treatment completion
5. Repeated testing during the same episode of diarrhea

Remember that laboratory testing alone cannot distinguish between asymptomatic colonization and clinical infection. The diagnosis of CDI requires both the presence of diarrhea and a positive test for toxigenic C. difficile or its toxins.