Diagnosis and Treatment of Clostridioides difficile Infection
The diagnosis of Clostridioides difficile infection (CDI) requires both clinical symptoms and laboratory confirmation, with treatment strategies based on disease severity, prior CDI history, and recurrence risk factors.
Diagnostic Approach
Clinical Assessment
- CDI should be suspected in patients with ≥3 unformed stools in 24 hours, especially with risk factors including recent antibiotic therapy, hospitalization, and advanced age 1
- Additional symptoms may include abdominal pain, cramps, bloating, ileus, and in severe cases, toxic megacolon 1
- Testing should only be performed on symptomatic patients with clinically significant diarrhea to avoid detecting asymptomatic colonization 2, 1
Laboratory Testing
- No single test can accurately diagnose CDI; a multistep algorithm is recommended for optimal detection 3
- Two main diagnostic approaches are recommended:
Two-Step Algorithm (Preferred)
- First step: High-sensitivity screening test using either:
- Second step: Confirmation with toxin A/B detection test (higher specificity) 2, 1
- This approach has excellent performance characteristics (sensitivity 0.91, specificity 0.98) 2
Single-Step PCR Testing
- Direct PCR testing for toxin genes (tcdA/tcdB) has high sensitivity and specificity (>0.90) 2
- However, this may detect asymptomatic carriers of toxigenic C. difficile 2
Reference Standards
- Toxigenic culture (TC) is the gold standard but is time-intensive and requires specialized equipment 2
- Cell culture cytotoxicity assay (CCA) is highly sensitive (0.94-1.00) and specific (0.99) for detecting toxins but has a slow turnaround time 2
Treatment Algorithm
Initial Management
- If possible, discontinue the inciting antibiotic therapy 1
- Avoid empirical therapy except in cases of strong suspicion of severe CDI 1
Treatment Based on Disease Severity
Mild to Moderate CDI (First Episode)
- Oral metronidazole 500 mg three times daily for 10 days is recommended as first-line therapy 1, 4
- Clinical improvement typically occurs within 3 days of starting treatment 4
Severe CDI
- Oral vancomycin 125 mg four times daily for 10 days is the treatment of choice 1, 5
- Clinical success rates of approximately 81% have been observed in clinical studies 1, 5
- Severe CDI is defined as ≥10 unformed bowel movements per day or WBC ≥15,000/mm³ 5
Recurrent CDI
- Fidaxomicin is recommended for patients with recurrent CDI or high risk of recurrence 2, 6, 7
- Fidaxomicin is a microbiome-sparing antibiotic that reduces the risk of disease recurrence 7
- Fecal microbiota transplantation (FMT) is effective for multiple recurrences 2, 7
Monitoring and Follow-Up
- Diarrhea and colitis typically improve within 3-5 days after starting appropriate treatment 5, 4
- Approximately 20-25% of patients experience recurrence after completing treatment 5, 4
- "Test of cure" is not recommended as patients may continue to shed C. difficile spores for up to six weeks after successful treatment 2
- Post-infectious irritable bowel syndrome can occur in about 4.3% of patients more than three months after infection 1
Prevention and Infection Control
- Rapid isolation of infected patients is crucial to control transmission 1
- Implement antimicrobial stewardship to reduce unnecessary antibiotic use 8
- Hand hygiene with soap and water (rather than alcohol-based sanitizers) is more effective for removing C. difficile spores 8
Common Pitfalls to Avoid
- Testing asymptomatic patients or those with formed stools can lead to detection of colonization rather than infection 2, 3
- Relying solely on toxin EIA testing has suboptimal sensitivity; repeat testing does not improve sensitivity 2
- Overuse of vancomycin may encourage proliferation of vancomycin-resistant nosocomial bacteria 4
- Failure to recognize severe disease may lead to inappropriate initial therapy with metronidazole instead of vancomycin 5