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

Treatment of Clostridioides difficile Infection

For C. difficile infection (CDI), oral vancomycin or fidaxomicin are the first-line treatments, with therapy selection based on disease severity, patient age, and recurrence status. 1

Initial Treatment Based on Severity

Non-severe CDI

• Adults:
  • Oral vancomycin 125 mg four times daily for 10 days OR
  • Fidaxomicin 200 mg twice daily for 10 days 1, 2
• Children (≥6 months):
  • Oral vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days OR
  • Metronidazole 7.5 mg/kg/dose (max 500 mg) three times daily for 10 days 1, 2

Severe CDI

• Adults: Oral vancomycin 125 mg four times daily for 10 days 1
• Children: Oral vancomycin 10 mg/kg/dose (max 500 mg) four times daily for 10 days with or without IV metronidazole 1

Fulminant CDI

• Oral vancomycin 500 mg four times daily PLUS
• Intravenous metronidazole 500 mg every 8 hours 1, 3
• Consider surgical consultation for possible colectomy if no improvement within 24-48 hours 1, 3

Treatment for Patients Unable to Take Oral Medications

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

Treatment for Recurrent CDI

First Recurrence

• If initially treated with metronidazole: Vancomycin 125 mg four times daily for 10 days 1
• If initially treated with vancomycin: Consider fidaxomicin 200 mg twice daily for 10 days 1, 4

Second or Subsequent Recurrences

• Vancomycin in a tapered and pulsed 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 1, 5
• OR Fidaxomicin 200 mg twice daily for 10 days 2, 4
• Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy for patients with multiple risk factors for recurrence 4

Multiple Recurrences

• Fecal microbiota transplantation (FMT) after failure of appropriate antibiotic treatments for at least two recurrences 1, 3, 5
• FMT has shown 70-90% clinical cure rates in recurrent and severe/fulminant CDI 3

Special Considerations

Pediatric Patients

• Fidaxomicin is FDA-approved for patients 6 months and older 1, 2
• Dosing should be weight-based for children 1

Inflammatory Bowel Disease with Colostomy

• Vancomycin is preferred over metronidazole 1
• Monitor for increased ostomy output, nausea, fever, and leukocytosis 1

Supportive Care

• Fluid and electrolyte replacement
• Albumin supplementation if severe hypoalbuminemia
• Avoid antiperistaltic agents and opiates 1

Prevention and Infection Control

• Contact precautions
• Hand hygiene with soap and water (alcohol-based sanitizers are less effective)
• Environmental cleaning with hypochlorite agents or sporicidal products 1
• Antibiotic stewardship to minimize use of high-risk antibiotics:
  • Clindamycin (highest risk)
  • Fluoroquinolones
  • Cephalosporins
  • Beta-lactam/beta-lactamase inhibitor combinations 1

Important Clinical Pitfalls

• Metronidazole is no longer recommended as first-line therapy for primary CDI in adults due to lower cure rates and higher recurrence rates 1, 4
• Testing should only be performed on symptomatic patients, as asymptomatic colonization is common 1, 6
• Patients should complete the full course of therapy even if symptoms improve to reduce risk of recurrence 2
• Early surgical consultation is crucial for fulminant CDI to prevent mortality 1, 3