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

Treatment for Clostridioides difficile (C. diff) Infection

Treatment for C. difficile infection should be based on disease severity, with oral vancomycin or fidaxomicin as first-line therapy for most cases, while metronidazole should be limited to mild-moderate cases in younger patients with few risk factors for recurrence. 1, 2, 3

Disease Severity Assessment

Severity assessment is crucial for determining appropriate treatment:

• Non-severe/Mild CDI: Stool frequency <4 times daily; no signs of severe colitis 1
• Severe CDI: One or more of the following markers 1, 2:
  • Fever >38.5°C
  • Hemodynamic instability
  • Leukocytosis >15×10^9/L
  • Creatinine rise >50% above baseline
  • Pseudomembranous colitis on endoscopy
  • Peritoneal signs, ileus, or toxic megacolon

Treatment Algorithm

Initial Episode Treatment

1. First step: Discontinue the inciting antibiotic if possible 1, 2

2. For non-severe CDI (when oral therapy is possible):

   • Vancomycin 125 mg four times daily orally for 10 days OR
   • Fidaxomicin 200 mg twice daily orally for 10 days 1, 2, 4, 3
   • (Metronidazole 500 mg three times daily orally for 10 days may be considered only in younger patients with mild disease and few risk factors) 3

3. For severe CDI (when oral therapy is possible):

   • Vancomycin 125 mg four times daily orally for 10 days OR
   • Fidaxomicin 200 mg twice daily orally for 10 days 1, 2

4. When oral therapy is impossible:

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

Recurrent CDI Treatment

1. First recurrence:

   • Vancomycin 125 mg four times daily orally for 10 days OR
   • Fidaxomicin 200 mg twice daily orally for 10 days 2, 3

2. Multiple recurrences:

   • Vancomycin with tapered/pulsed regimen OR
   • Fidaxomicin 200 mg twice daily orally for 10 days OR
   • Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy with standard antibiotics 1, 2, 3
   • Fecal microbiota transplantation (FMT) for patients with multiple recurrences who have failed appropriate antibiotic treatments 1, 2, 3

Fulminant CDI/Surgical Considerations

Early surgical consultation should be obtained for patients with:

• Perforation of the colon
• Systemic inflammation not responding to antibiotics
• Toxic megacolon
• Severe ileus 1

Important Considerations

1. Avoid:

   • Antiperistaltic and opiate agents, especially in acute settings 1, 2
   • Unnecessary proton pump inhibitors (PPIs) 1

2. Infection Control:

   • Hand hygiene with soap and water (alcohol-based sanitizers may not kill C. difficile spores) 1
   • Contact precautions and isolation 1
   • Thorough environmental cleaning and disinfection 1

3. Monitoring:

   • Assess treatment response within 3 days (expect decreased stool frequency and improved consistency) 2
   • Monitor for recurrence for up to 2 months after treatment 2
   • Pay special attention to patients over 65 years, those with severe underlying disease, or continued antibiotic use 2

Special Populations

• Children: Fidaxomicin is FDA-approved for patients aged 6 months and older 4
• Elderly patients: Higher risk for complications and recurrence; monitor renal function during vancomycin treatment 2
• Immunocompromised patients: Consider bezlotoxumab to prevent recurrences 1

The treatment landscape for C. difficile has evolved significantly, with metronidazole no longer recommended as first-line therapy for most adults, and increasing evidence supporting the use of fidaxomicin and fecal microbiota transplantation in appropriate clinical scenarios 3, 5.