Management of Positive C. difficile PCR for Binary Toxins Only

Diagnostic Interpretation

Patients who are positive by PCR 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) 1
Patients who are positive only by molecular methods but negative for toxins should be considered "excretors" who may present an infection control risk but generally do not require treatment 2

Evaluate for clinical symptoms consistent with CDI, including ≥3 unformed bowel movements in 24 hours 3
Abdominal pain, fever, and leukocytosis are symptoms consistent with CDI 4
Recent antibiotic exposure is an important risk factor for CDI 5
The severity of symptoms correlates more strongly with the presence of toxins A and B than with PCR positivity alone 6

Observation without antimicrobial treatment is recommended for asymptomatic patients or those with mild symptoms 2
Implement contact precautions to prevent transmission 7
Do not repeat testing within 7 days unless there is a clear change in clinical presentation 3
Consider empiric therapy while awaiting additional test results if there is strong clinical suspicion for CDI despite absence of toxins A and B 5
Discontinue inciting antibiotics if possible 5
Consider alternative testing methods such as toxin EIA or cell cytotoxicity neutralization assay (CCNA) 7
Flexible sigmoidoscopy may be helpful in diagnosis when there is high clinical suspicion 5

For mild-moderate disease, oral metronidazole 500 mg three times daily for 10 days is a treatment option 5
For severe disease or non-response to metronidazole, oral vancomycin 125 mg four times daily for 10 days is a treatment option 5

PCR tests are highly sensitive but may detect colonization rather than active infection 3
Multi-step algorithms provide better clinical correlation than PCR/NAAT alone 8
Toxin-positive patients have higher rates of complications, mortality, and recurrence than those who are PCR-positive but toxin-negative 6
Avoid repeated testing within the same episode of diarrhea as this increases the risk of false-positive results 3
Consider alternative causes of diarrhea in PCR-positive, toxin-negative patients 4

No need for test of cure as >60% of patients may remain C. difficile positive even after successful treatment 3
Implement antimicrobial stewardship to reduce risk of recurrence 5
Consider discontinuing unnecessary proton pump inhibitors 5

Patients who are PCR-positive and antigen-positive but toxin-negative should generally NOT be treated, as they likely represent colonization or "excretors" rather than true infection, unless there are specific high-risk clinical features present, according to the Infectious Diseases Society of America 9
Toxin-positive patients had 16.6% mortality versus 9.7% in toxin-negative/PCR-positive patients (P = .022), with the toxin-negative group not significantly different from controls at 8.6%, as reported by the Clinical Infectious Diseases journal 9

High-risk features suggesting treatment may be warranted (even if toxin-negative) include significant leukocytosis or rising creatinine, as stated by the Clinical Infectious Diseases journal 9
Features suggesting colonization (no treatment needed) include minimal diarrhea or non-diarrheal stool, absence of fecal inflammation, and alternative explanation for symptoms, according to the JAMA journal 10

For most PCR+/Antigen+/Toxin- patients (low-risk), do NOT treat with antibiotics, as recommended by the Clinical Infectious Diseases journal 9
For high-risk PCR+/Antigen+/Toxin- patients, consider empiric treatment with oral vancomycin 125 mg four times daily for 10 days, as suggested by the JAMA journal 11, 10

The World Health Organization recommends testing only unformed, diarrheal stools to avoid false-positive results that can lead to unnecessary antibiotic therapy 12
The Centers for Disease Control and Prevention suggest that up to 7% of hospitalized patients are colonized with C. difficile without disease, and therefore, asymptomatic patients should not be tested 12

The Society for Healthcare Epidemiology of America recommends maintaining contact precautions regardless of treatment decision to prevent transmission of C. difficile to others 12