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

Treatment of Clostridioides difficile Infection (C. diff)

For C. diff infection, treatment should be based on disease severity, with oral vancomycin or fidaxomicin as first-line therapy for most cases, while metronidazole should be limited to non-severe initial episodes only. 1

Initial Treatment Based on Disease Severity

Non-severe C. diff infection:

• Metronidazole 500 mg orally three times daily for 10 days (if oral therapy is possible) 1
• For patients unable to take oral medication: metronidazole 500 mg intravenously three times daily for 10 days 1
• Mild cases clearly induced by antibiotics may be treated by stopping the inciting antibiotic, but patients must be monitored closely for clinical deterioration 1

Severe C. diff infection:

• Vancomycin 125 mg orally four times daily for 10 days 1
• For patients unable to take oral medication: metronidazole 500 mg intravenously 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 by nasogastric tube 1
• Fidaxomicin 200 mg orally twice daily for 10 days is an alternative to vancomycin with fewer recurrences 1, 2

Criteria for Severe C. diff Infection

• Marked leukocytosis (WBC >15 × 10^9/L) 1
• Serum albumin <30 g/L 1
• Rise in serum creatinine (≥133 μM or ≥1.5 times premorbid level) 1
• Pseudomembranous colitis on endoscopy 1
• Toxic megacolon or severe ileus 1
• Advanced age and significant comorbidities may also be considered markers of severe disease 1

Treatment of Recurrent C. diff Infection

First recurrence:

• Treat as an initial episode based on severity (same regimen as above) 1
• If disease has progressed from non-severe to severe, use the severe treatment protocol 1

Second and subsequent recurrences:

• Vancomycin 125 mg orally four times daily for at least 10 days 1
• Consider a vancomycin taper/pulse strategy after the initial course 1
• Fidaxomicin 200 mg twice daily for 10 days is particularly effective for preventing further recurrences 1, 3
• Fecal microbiota transplantation (FMT) should be considered for multiple recurrences that have failed appropriate antibiotic therapy 1, 4

Adjunctive Therapies

• Bezlotoxumab (monoclonal antibody against C. diff toxin B) may prevent recurrences, particularly in high-risk patients 1, 5
• Discontinue the inciting antibiotic if possible, as continued use significantly increases risk of recurrence 1
• If continued antibiotic therapy is required, use agents less frequently associated with CDI (aminoglycosides, sulfonamides, macrolides) 1

Surgical Management

• Surgical consultation should be obtained early for patients with severe CDI who develop systemic toxicity 1
• Indications for surgery include: 1
  • Perforation of the colon
  • Systemic inflammation with deteriorating clinical condition despite antibiotic therapy
  • Toxic megacolon or severe ileus
• Total colectomy has been the traditional surgical approach, but diverting loop ileostomy with colonic lavage is emerging as a viable alternative with potentially lower mortality 1, 6
• Surgery should be performed before the disease becomes too advanced; serum lactate >5.0 mmol/L is associated with higher mortality 1

Important Considerations and Pitfalls

• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 1
• Metronidazole should be limited to initial episodes of non-severe CDI due to lower efficacy in severe disease 1, 6
• Treatment response should be assessed after at least 3 days, as improvement with metronidazole may take 3-5 days 1
• For patients requiring continued antibiotics, use the narrowest spectrum possible to reduce risk of recurrence 1
• Hand hygiene with soap and water (not alcohol-based sanitizers) is essential for preventing transmission, as alcohol does not kill C. diff spores 1