Interpretation of Toxin A Positive, Toxin B Negative Result
A positive toxin A with negative toxin B result is highly unusual and should prompt immediate verification of the test methodology, as this pattern is extremely rare in clinical practice and may represent a testing error or the presence of a toxin A-negative, toxin B-positive (A-B+) strain that was misreported. 1
Understanding the Clinical Context
The scenario you describe (toxin A positive, toxin B negative) contradicts the typical biology of C. difficile:
- Both toxin A and toxin B are essential virulence factors that can independently cause fulminant disease in animal models, and strains producing either toxin alone remain pathogenic 2
- Toxin A-negative, toxin B-positive (A-B+) strains are well-documented and have been isolated with increasing frequency worldwide, causing clinically significant diarrhea and colitis 1
- However, toxin A-positive, toxin B-negative strains are essentially non-existent in clinical practice, as the toxin genes are typically co-regulated 2
Diagnostic Approach
Verify Testing Methodology
- Confirm that your laboratory uses assays detecting both toxin A AND toxin B, as older diagnostic methods that only detected toxin A would miss A-B+ strains entirely 1
- Request repeat testing or use an alternative testing platform to rule out technical error, as this result pattern is biologically implausible 3
- Consider using a multi-step algorithm (GDH plus toxin A/B EIA, or GDH plus toxin arbitrated by NAAT) rather than relying on a single test result 3
Clinical Assessment While Awaiting Confirmation
- Evaluate for ≥3 unformed bowel movements in 24 hours that conform to the container shape 4
- Assess for high-risk features including significant leukocytosis (WBC ≥15,000/mm³), rising serum creatinine, fever, or severe abdominal pain 5
- Review recent antibiotic exposure within the past 8 weeks, particularly clindamycin, cephalosporins, or penicillins 6, 7
Treatment Decision Algorithm
If Clinical Suspicion for CDI is High (Severe Symptoms Present)
- Initiate empiric treatment with oral vancomycin 125 mg four times daily for 10 days while awaiting confirmatory testing, as severe illness warrants treatment before complete diagnostic workup 5
- Do not delay treatment in patients with severe leukocytosis, rising creatinine, or hemodynamic instability 5
If Clinical Suspicion is Low to Moderate
- Withhold antibiotics pending repeat or confirmatory testing using NAAT or cell cytotoxicity neutralization assay (CCNA) 3
- Implement contact precautions regardless of treatment decision to prevent potential transmission 5
- Consider alternative causes of diarrhea including medication effects, enteral feeding, or other infectious etiologies 5
Key Pitfalls to Avoid
- Never rely on toxin A detection alone, as this will miss the clinically important A-B+ strains that cause genuine disease 1
- Do not repeat testing within 7 days of the initial test during the same diarrheal episode, as this increases false-positive results and has only 2% diagnostic yield 8
- Avoid testing asymptomatic patients or those without diarrhea, as this detects colonization rather than infection 3, 8
Most Likely Explanation
The most probable scenario is that you are dealing with an A-B+ strain where toxin B is actually present but was reported incorrectly, or your laboratory's assay has technical limitations. 1 True toxin A-positive, toxin B-negative strains producing clinical disease have not been documented in the medical literature, making this result highly suspect for laboratory error.