How to manage a patient with a positive Clostridioides difficile (C. diff) polymerase chain reaction (PCR) result for binary toxins only, without evidence of toxins A and B?

Management of Positive C. difficile PCR for Binary Toxins Only

Patients with a positive C. difficile PCR for binary toxins only, without evidence of toxins A and B, should be considered potential carriers rather than active infection cases and generally do not require treatment unless they have severe clinical symptoms consistent with CDI.

Diagnostic Interpretation

• PCR tests that detect only binary toxins without toxins A and B represent an uncommon finding, as most pathogenic C. difficile strains produce both toxin A and toxin B, which are the primary virulence factors 1
• Studies show that patients who are positive by PCR (detecting toxigenic C. difficile) but negative for toxins have significantly lower rates of complications compared to those positive for both PCR and toxins (3% vs 39%, p<0.001) 2
• Patients who are positive only by molecular methods (NAAT/PCR) but negative for toxins should be considered "excretors" who may present an infection control risk but generally do not require treatment 2

Clinical Assessment

• Evaluate for clinical symptoms consistent with CDI:
  • ≥3 unformed bowel movements in 24 hours 2
  • Abdominal pain, fever, leukocytosis 2
  • Recent antibiotic exposure (important risk factor) 2
• The severity of symptoms correlates more strongly with the presence of toxins A and B than with PCR positivity alone 2
• Binary toxin alone has not been definitively established as a primary cause of C. difficile-associated disease, though it may be a co-factor in virulence 3, 4

Management Approach

For Asymptomatic Patients or Mild Symptoms:

• Observation without antimicrobial treatment is recommended 2
• Implement contact precautions to prevent transmission 2
• Do not repeat testing within 7 days unless there is a clear change in clinical presentation 2

For Patients with Moderate-Severe Symptoms:

• If there is strong clinical suspicion for CDI despite absence of toxins A and B:
  • Consider empiric therapy while awaiting additional test results 2
  • Discontinue inciting antibiotics if possible 2
  • Consider alternative testing methods such as toxin EIA or cell cytotoxicity neutralization assay (CCNA) 2
  • Flexible sigmoidoscopy may be helpful in diagnosis when there is high clinical suspicion 2

Treatment Options (if clinically indicated):

• For mild-moderate disease: Oral metronidazole 500 mg three times daily for 10 days 2
• For severe disease or non-response to metronidazole: Oral vancomycin 125 mg four times daily for 10 days 2, 5
• For recurrent or severe complicated cases: Consider fidaxomicin 200 mg twice daily for 10 days 6

Important Considerations

• Diagnostic pitfall: PCR tests are highly sensitive but may detect colonization rather than active infection 2
• Multi-step algorithms (GDH plus toxin, or NAAT plus toxin) provide better clinical correlation than PCR/NAAT alone 2
• Toxin-positive patients have higher rates of complications, mortality, and recurrence than those who are PCR-positive but toxin-negative 2
• Avoid repeated testing within the same episode of diarrhea as this increases the risk of false-positive results 2
• Consider alternative causes of diarrhea in PCR-positive, toxin-negative patients 2

Follow-up

• Monitor clinical response if treatment is initiated
• No need for test of cure as >60% of patients may remain C. difficile positive even after successful treatment 2
• Implement antimicrobial stewardship to reduce risk of recurrence 2
• Consider discontinuing unnecessary proton pump inhibitors 2