What is the treatment for Clostridioides difficile (C. diff) infection?

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of Clostridioides difficile infection, oral vancomycin 125 mg four times daily for 10 days is recommended as first-line therapy for both initial and first recurrent episodes, with treatment selection based on disease severity. 1

Disease Severity Assessment

Before initiating treatment, assess CDI severity:

• Non-severe CDI: Absence of markers of severe disease
• Severe CDI: Presence of one or more of:
  • Marked leukocytosis (WBC >15,000 cells/mL)
  • Decreased blood albumin
  • Rise in serum creatinine
  • Advanced age with significant comorbidities 1
• Fulminant CDI: Hypotension, shock, ileus, or megacolon 2

Treatment Algorithm by Severity

Initial Episode - Non-severe CDI

1. First-line: Oral vancomycin 125 mg four times daily for 10 days 1
2. Alternative: Fidaxomicin 200 mg twice daily for 10 days 1
3. If oral therapy not possible: Intravenous metronidazole 500 mg three times daily for 10 days 2

While earlier guidelines recommended metronidazole for non-severe cases, more recent evidence supports vancomycin or fidaxomicin as preferred first-line agents due to superior efficacy 1.

Initial Episode - Severe CDI

1. First-line: Oral vancomycin 125 mg four times daily for 10 days 2, 1
2. Alternative: Fidaxomicin 200 mg twice daily for 10 days 1
3. If oral therapy not possible: Intravenous metronidazole 500 mg three times daily for 10 days PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily via nasogastric tube 2, 1

Fulminant CDI

1. First-line: Oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg three times daily 1
2. If ileus present: Add intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 2, 1
3. Surgical consultation: Should be obtained promptly for patients with:
   • Perforation of the colon
   • Systemic inflammation not responding to antibiotic therapy
   • Toxic megacolon
   • Severe ileus 1

Early surgical intervention can reduce mortality in severe cases. Consider colectomy before serum lactate exceeds 5.0 mmol/L 2.

Management of Recurrent CDI

First Recurrence

Treat as per initial episode based on severity assessment 2, 1

Second or Subsequent Recurrences

1. First-line: Vancomycin taper/pulse regimen:

   • 125 mg four times daily for 10-14 days, then
   • 125 mg twice daily for 7 days, then
   • 125 mg once daily for 7 days, then
   • 125 mg every 2-3 days for 2-8 weeks 2, 1

2. Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

3. For multiple recurrences: Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment failures (success rates up to 90%) 1, 3

4. Adjunctive therapy: Bezlotoxumab (monoclonal antibody against C. difficile toxin B) can be considered, especially in immunocompromised patients 1, 4

Special Considerations

Pediatric Patients

• For children ≥6 months of age:
  • Non-severe CDI: Either metronidazole or vancomycin can be used 2
  • Severe CDI: Oral vancomycin is recommended 2
  • Fulminant CDI: Add intravenous metronidazole to oral vancomycin 2
  • Multiple recurrences: Consider vancomycin extended regimen or FMT 2

Elderly Patients

• Higher risk for recurrence (RR = 1.63)
• Consider early use of vancomycin or fidaxomicin 1
• May benefit from adjunctive bezlotoxumab to prevent recurrence 1

Additional Management Strategies

1. Discontinue the inciting antibiotic if possible 2, 1
2. Avoid antiperistaltic agents and opiates, especially in acute setting 2
3. Review and discontinue proton pump inhibitors if not medically necessary 1
4. Infection control measures:
   • Isolate patients until 48 hours after diarrhea resolution
   • Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores)
   • Environmental cleaning with sporicidal agents 1

Prophylaxis for Patients with History of CDI

Consider prophylactic low-dose vancomycin (125 mg daily) during future antibiotic courses for patients with a history of CDI 1

Common Pitfalls to Avoid

1. Continuing unnecessary antibiotics during CDI treatment
2. Delaying surgical consultation in fulminant cases
3. Using metronidazole as first-line therapy for severe CDI
4. Failing to recognize severity markers that would indicate need for more aggressive therapy
5. Not implementing appropriate infection control measures to prevent transmission

Remember that C. difficile infection has a high recurrence rate (up to 25% in elderly patients), and each recurrence increases the risk of further episodes 1. Early recognition of severity and appropriate treatment selection are crucial for improving outcomes.