Explaining a Positive C. difficile Gene Test with Pending Toxin Results
Your patient has tested positive for the C. difficile gene (PCR/NAAT), which means the bacteria is present in their stool, but we are waiting for toxin results to determine if they have active infection requiring treatment versus simple colonization.
What the Positive Gene Test Means
- The PCR/NAAT test detects the genetic material of C. difficile bacteria with very high sensitivity (93-94%), but it cannot distinguish between active infection and harmless colonization 1
- Approximately 44-55% of patients who test positive by PCR will be negative for toxins, representing colonization rather than true infection 1, 2
- The presence of C. difficile bacteria alone does not necessarily mean disease—the toxins are what cause symptoms and complications 3, 4
Why the Toxin Test Matters
- Patients who are both gene-positive AND toxin-positive have significantly worse outcomes: 7.6% complication rate, 8.4% mortality, and longer duration of diarrhea 1, 2
- Patients who are gene-positive but toxin-negative have minimal complications: 0% complication rate in the largest study, 0.6% mortality, and outcomes similar to patients without C. difficile at all 1, 2
- The toxin test tells us whether the bacteria is actively producing the harmful substances that cause disease 5, 3
What Happens While We Wait
Clinical Assessment to Guide Interim Management
Evaluate these specific factors that suggest true infection:
- Diarrhea severity: ≥3 unformed stools in 24 hours that conform to the container shape 1
- Laboratory markers: White blood cell count >15,000 cells/μL or rising serum creatinine 5, 6
- Clinical symptoms: Abdominal pain, fever, or signs of severe colitis 6
- Recent antibiotic exposure: Strong risk factor for true CDI 1
Management Strategy Based on Clinical Severity
For patients with mild symptoms and low clinical suspicion:
- Observation without antibiotics is appropriate while awaiting toxin results 6, 7
- Implement contact precautions to prevent potential transmission 6
- Discontinue inciting antibiotics if medically feasible 6
For patients with severe illness (high fever, significant leukocytosis, rising creatinine, or severe diarrhea):
- Consider empiric treatment with oral vancomycin 125 mg four times daily while awaiting toxin results 1, 6
- Severe illness warrants treatment even before confirmatory testing is complete 1
What the Final Toxin Result Will Tell Us
If Toxin is Positive (Gene+/Toxin+)
- This confirms active C. difficile infection requiring full treatment 5
- Continue or initiate appropriate antibiotic therapy 5
- Higher risk for complications and recurrence 1
If Toxin is Negative (Gene+/Toxin-)
- This likely represents colonization or "excretor" status rather than true infection 5, 6
- Treatment is generally NOT recommended unless high-risk features are present 6, 2
- Outcomes are similar to patients without C. difficile when toxin is absent 2, 7
- Continue contact precautions as the patient may still transmit bacteria to others 6
- Investigate alternative causes of diarrhea 6
Critical Pitfalls to Avoid
- Do not repeat testing within 7 days of the initial test during the same diarrheal episode—this increases false-positive results and has only 2% diagnostic yield 1
- Do not treat based on gene test alone without considering toxin status and clinical context—this leads to overdiagnosis and overtreatment 2
- Do not perform test of cure after treatment, as >60% of successfully treated patients remain PCR-positive 5, 6
Key Message for Your Patient
"We found C. difficile bacteria in your stool, but we need to know if it's making toxins that cause disease. Many people carry this bacteria harmlessly. The toxin test will help us decide if you need antibiotics or if we should look for other causes of your symptoms. If you're feeling very ill, we may start treatment now while waiting for results, but if your symptoms are mild, it's often safer to wait for the toxin results before deciding on antibiotics." 5, 6, 2