Treatment Decision for C. difficile PCR-Positive/EIA-Negative Patients
In most cases, you should NOT treat a patient who is C. difficile PCR-positive but toxin EIA-negative, as this likely represents colonization rather than active infection. 1
Understanding the Diagnostic Discordance
The key issue is that PCR tests detect the presence of toxin genes, not actual toxins, which means they identify both active infection and asymptomatic colonization. 2 The toxin EIA, while less sensitive, detects actual toxins in stool and correlates better with clinically significant disease. 2
- PCR-positive/EIA-negative patients have significantly lower complication rates (3% vs 39%, p<0.001) compared to patients who are positive for both tests. 1
- These patients should be considered "excretors" who pose an infection control risk but generally do not require treatment. 1
- Toxin-positive patients have 16.6% mortality versus 9.7% in toxin-negative/PCR-positive patients (P = 0.022), with the toxin-negative group not significantly different from controls at 8.6%. 1
Clinical Assessment Algorithm
Before deciding on treatment, evaluate for high-risk clinical features:
Features Suggesting True Infection (Consider Treatment):
- Significant leukocytosis (WBC ≥15,000/µL) 1, 3
- Rising serum creatinine 1
- Baseline severe disease by IDSA criteria (≥10 unformed stools/day or WBC ≥15,000/mm³) 3
- Fulminant colitis (peritoneal signs, ileus, toxic megacolon) 3
- Fever >38.5°C 3
- Proton pump inhibitor use (associated with increased complications) 3
Features Suggesting Colonization (No Treatment Needed):
- Minimal diarrhea or non-diarrheal stool 1
- Absence of fecal inflammation 1
- Alternative explanation for symptoms 1
- Absence of clinical symptoms (no abdominal pain, fever, or significant leukocytosis) 1
Treatment Recommendations
For Low-Risk PCR+/EIA- Patients (Majority):
Do NOT initiate antibiotic treatment. 1 Instead:
- Implement contact precautions to prevent transmission 1
- Discontinue inciting antibiotics if possible 1
- Observe clinically without antimicrobial treatment 1
- Do not repeat testing within 7 days unless there is a clear change in clinical presentation 1
For High-Risk PCR+/EIA- Patients:
If multiple high-risk features are present (severe leukocytosis, rising creatinine, fulminant colitis, fever >38.5°C), consider empiric treatment with oral vancomycin 125 mg four times daily for 10 days. 1, 4
Critical Pitfalls to Avoid
- Do not reflexively treat all PCR-positive results, as this leads to overtreatment of colonized patients. 2, 1
- Do not perform "test of cure" after treatment, as >60% of patients remain C. difficile positive even after successful treatment. 2, 1
- Do not repeat testing during the same diarrheal episode unless clinical status changes significantly, as this increases false-positive results. 1, 5
- Recognize that NAAT/PCR alone has high sensitivity but may detect colonization rather than active infection. 2
Infection Control Regardless of Treatment Decision
Even if you do not treat, implement strict infection control measures:
- Contact precautions with gown and gloves 4
- Handwashing with soap and water (alcohol does not inactivate C. difficile spores) 4
- Patient isolation or cohorting 2
Supporting Evidence on Outcomes
Research demonstrates that PCR+/EIA- patients who received complete treatment had similar outcomes to PCR+/EIA+ patients (11% vs 13% CDI-related complications, 17% vs 18% 60-day mortality, 7% vs 9% recurrence), but this does not justify routine treatment of all PCR+/EIA- patients. 3 The key is identifying the subset with true disease based on clinical features, not treating all positive PCR results indiscriminately. 3