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

Treatment of Clostridioides difficile Colitis

For C. difficile colitis treatment, oral vancomycin or fidaxomicin is now recommended as first-line therapy for initial episodes, with treatment selection based on disease severity and recurrence risk. 1

Initial Treatment Algorithm Based on Disease Severity

Non-severe C. difficile infection:

• First-line options:
  • Vancomycin 125 mg orally four times daily for 10 days (A-I) 1
  • Fidaxomicin 200 mg orally twice daily for 10 days (B-I) 1, 2
  • Note: Metronidazole is no longer recommended as first-line therapy for adults 3

Severe C. difficile infection:

• First-line: Vancomycin 125 mg orally four times daily for 10 days (A-I) 1
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2

When oral therapy is impossible:

• Non-severe: Metronidazole 500 mg IV three times daily for 10 days (A-III) 1
• Severe: Metronidazole 500 mg IV three times daily for 10 days (A-III) PLUS either:
  • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours (C-III) AND/OR
  • Vancomycin 500 mg four times daily via nasogastric tube (C-III) 1

Assessing Disease Severity

Signs of severe colitis include:

• Fever >38.5°C
• Hemodynamic instability or septic shock
• Leukocytosis >15 × 10^9/L
• Serum creatinine >50% above baseline
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Radiologic evidence of colonic distension, wall thickening, or pericolonic fat stranding 1

Treatment of Recurrent C. difficile Infection

First recurrence:

• Treat as an initial episode based on severity 1

Second and subsequent recurrences:

• First choice: Vancomycin 125 mg orally four times daily for at least 10 days, followed by a taper/pulse strategy (B-II) 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1, 2
• Consider: Bezlotoxumab (a monoclonal antibody against C. difficile toxin B) as adjunctive therapy for patients with multiple risk factors for recurrence 4
• For multiple recurrences: Fecal microbiota transplantation (FMT) has shown high cure rates (>85%) and should be offered to patients with frequently recurring CDI 1, 4

Surgical Management

Colectomy should be performed in cases of:

• Perforation of the colon
• Systemic inflammation and deteriorating clinical condition despite maximal antibiotic therapy
• Toxic megacolon or severe ileus

Important: Surgery should be performed before colitis becomes very severe. Serum lactate >5.0 mmol/L indicates advanced disease with higher surgical mortality 1

Important Considerations and Pitfalls

1. Discontinue the inciting antibiotic if possible, as this alone may resolve mild CDI in some cases 1

2. Avoid antiperistaltic agents and opiates as they can mask symptoms and potentially worsen disease 1

3. Do not use metronidazole for initial treatment in adults unless other options are unavailable, as it has been shown to be inferior to vancomycin and fidaxomicin 4, 3

4. Infection control measures are critical to prevent transmission:

   • Hand hygiene with soap and water (preferred over alcohol-based sanitizers during outbreaks)
   • Isolation of infected patients
   • Environmental cleaning with sporicidal agents 1

5. Monitor for treatment response, defined as decreased stool frequency and improved consistency after 3 days of therapy 1

6. Prophylactic antibiotics are not recommended for prevention of CDI 1

7. Probiotics are not recommended by the Infectious Diseases Society of America for prevention of CDI 3

The treatment landscape for C. difficile infection has evolved significantly, with vancomycin and fidaxomicin now forming the cornerstone of therapy, and fecal microbiota transplantation emerging as an effective option for recurrent cases 4.