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

Treatment of Clostridioides difficile Infection

For C. difficile infection, oral vancomycin is the recommended first-line treatment for severe cases, while oral metronidazole can be used for mild to moderate cases, with fidaxomicin as an alternative for patients at high risk of recurrence. 1

Initial Assessment and Classification

Treatment should be based on disease severity:

• Non-severe CDI: <4 stools/day, no signs of severe colitis
• Severe CDI: Presence of any of these markers:
  • WBC >15,000 cells/mm³
  • Serum creatinine >1.5 times baseline
  • Hypotension or shock
  • Ileus or toxic megacolon

First-Line Treatment Algorithm

Non-severe CDI (Initial Episode)

• First choice: Metronidazole 500 mg orally three times daily for 10 days 1
• Alternative: Vancomycin 125 mg orally four times daily for 10 days 1

Severe CDI (Initial Episode)

• First choice: Vancomycin 125 mg orally four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2

Fulminant CDI (Severe with complications)

• Vancomycin 500 mg orally four times daily 1
• PLUS Metronidazole 500 mg intravenously every 8 hours 1
• Consider intracolonic vancomycin 500 mg in 100 mL saline as enema every 4-12 hours if ileus present 1

Management of Recurrent CDI

First Recurrence

• Treat as per initial episode based on severity 1
• If disease has progressed from non-severe to severe, use vancomycin 1

Second or Subsequent Recurrences

• Vancomycin 125 mg orally four times daily for at least 10 days 1
• Consider vancomycin taper/pulse strategy:
  • Example taper: Decreasing daily dose with 125 mg every 3 days 1
  • Example pulse: 125 mg every 3 days for 3 weeks 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1
• For multiple recurrences: Consider fecal microbiota transplantation (FMT) 1

Special Situations

When Oral Therapy Is Impossible

• Non-severe: Metronidazole 500 mg intravenously three times daily for 10 days 1
• Severe: Metronidazole 500 mg intravenously three times daily PLUS intracolonic vancomycin 500 mg in 100 mL saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 1

Surgical Indications

Colectomy should be performed in:

• Perforation of the colon
• Systemic inflammation with deteriorating clinical condition not responding to antibiotics
• Toxic megacolon or severe ileus
• Consider surgery before serum lactate exceeds 5.0 mmol/L 1

Adjunctive Therapies

• Bezlotoxumab: Consider for patients at high risk for recurrence, especially immunocompromised patients or those with severe CDI 1
• Tigecycline: Consider only for patients who have failed standard treatments and have limited options 1
• Probiotics: Limited evidence supports their use as adjunctive treatment 1

Important Considerations

• Discontinue the inciting antibiotic as soon as possible 1
• Avoid antiperistaltic agents and opiates 1
• Provide supportive care including fluid resuscitation and electrolyte replacement 1
• For severe cases, consider albumin supplementation if hypoalbuminemia (<2 g/dL) is present 1

Common Pitfalls to Avoid

1. Diagnostic errors: Only test symptomatic patients (≥3 unformed stools in 24 hours) as testing cannot distinguish between colonization and infection 1
2. Inappropriate treatment selection: Using metronidazole for severe cases or multiple recurrences 1
3. Delayed surgical consultation: Failure to involve surgeons early in fulminant cases 1
4. Inadequate supportive care: Neglecting fluid resuscitation and electrolyte replacement 1
5. "Test of cure": This is not recommended after CDI treatment 1

The treatment approach should be promptly initiated based on clinical presentation, with adjustments made as needed based on patient response and disease severity.