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

Treatment of Clostridioides difficile Infection

For all cases of C. difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days is the first-line treatment due to its superior clinical cure rates compared to metronidazole. 1

Initial Treatment Based on Disease Severity

Non-severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days (especially for patients at higher risk of recurrence) 1, 2
• If limited access to vancomycin/fidaxomicin: Metronidazole 500 mg three times daily for 10 days 1

Severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days 1

Patients Unable to Take Oral Medications

• Intravenous metronidazole 500 mg three times daily for 10 days PLUS one of the following:
  • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours
  • Vancomycin 500 mg four times daily via nasogastric tube 1

Treatment of Recurrent CDI

First Recurrence

• Same treatment as initial episode based on severity 1

Second or Subsequent Recurrences

• Oral vancomycin 125 mg four times daily for at least 10 days, with consideration of vancomycin taper/pulse strategy after standard course 1
• Fidaxomicin may be preferred over vancomycin due to lower recurrence rates 1, 3
• For multiple recurrences: Consider fecal microbiota transplantation (FMT) after failure of appropriate antibiotic treatments (70-90% clinical cure rates) 1, 4, 5
• Adjunctive therapy: Bezlotoxumab (monoclonal antibody against C. difficile toxin B) to reduce recurrence risk 1, 5

Monitoring Response to Treatment

• Daily assessment of:
  • Frequency and consistency of bowel movements
  • Abdominal pain and cramping
  • Fever 1
• Laboratory monitoring:
  • Complete blood count
  • Serum creatinine
  • Electrolytes 1
• Confirmation of resolution:
  • No diarrhea for at least 48 hours
  • Resolution of abdominal pain and fever
  • Normalization of laboratory values
  • Negative follow-up C. difficile testing 1

Special Considerations and Precautions

Risk Factors for Increased Absorption/Toxicity

• Inflammatory bowel disorders may increase systemic absorption of oral vancomycin
  • Monitor serum vancomycin levels in these patients, especially with renal insufficiency 1
• Patients >65 years have increased nephrotoxicity risk
  • Monitor renal function during and after treatment 1

Prevention Strategies

• Discontinue or narrow the spectrum of other antibiotics whenever possible 1
• All patients with acute colitis should receive low molecular weight heparin for thromboprophylaxis 1
• For patients with multiple recurrences who have failed other treatments, consider prolonged vancomycin at 125 mg once daily as secondary prophylaxis 1

Common Pitfalls to Avoid

1. Delayed treatment escalation: Delaying appropriate escalation of therapy can increase morbidity and mortality 1

2. Antibiotic selection: Certain antibiotics significantly increase CDI risk:

   • Clindamycin (highest risk)
   • Fluoroquinolones
   • Cephalosporins
   • Beta-lactam/beta-lactamase inhibitor combinations 1

3. Inappropriate use of metronidazole: Vancomycin is superior to metronidazole in all cases of CDI, with better clinical cure rates 1, 5

4. Failure to recognize severe disease: Severe cases require prompt and aggressive treatment to prevent complications

5. Overuse of vancomycin: While effective, widespread use may encourage proliferation of vancomycin-resistant bacteria; use fidaxomicin when appropriate, especially for recurrence prevention 5, 3