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

Treatment of Clostridioides difficile Infection

For C. difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days is recommended as first-line therapy, with treatment selection based on disease severity and recurrence risk. 1

Classification and Initial Assessment

Disease Severity Categories

• Non-severe CDI: Stool frequency < 4 times daily; no signs of severe colitis
• Severe CDI: White blood cell count > 15,000 cells/mm³, serum creatinine > 1.5 mg/dL, or signs of severe colitis
• Fulminant CDI: Hypotension, shock, ileus, or toxic megacolon

Risk Factors for Recurrence

• Age > 65 years
• Immunodeficiency
• Continued use of inciting antibiotics
• Comorbidities (inflammatory bowel disease)
• Previous CDI episodes
• Hypoalbuminemia

Treatment Algorithm

Initial Episode Treatment

1. First step: Discontinue the inciting antibiotic whenever possible 1

2. Non-severe CDI:

   • First choice: Vancomycin 125 mg four times daily orally for 10 days OR fidaxomicin 200 mg twice daily orally for 10 days 1
   • Alternative: Metronidazole 500 mg three times daily orally for 10 days (only if vancomycin/fidaxomicin unavailable) 2, 1

3. Severe CDI:

   • Vancomycin 125 mg four times daily orally for 10 days 2, 1
   • Consider fidaxomicin 200 mg twice daily orally for 10 days (especially with recurrence risk factors) 1, 3

4. Fulminant CDI:

   • Vancomycin 500 mg four times daily orally or via nasogastric tube 1
   • PLUS intravenous metronidazole 500 mg every 8 hours 1
   • Consider intracolonic vancomycin 500 mg in 100 mL saline every 4-12 hours if ileus present 2, 1
   • Surgical consultation for potential colectomy if clinical deterioration 2, 1

Recurrent CDI Treatment

1. First recurrence:

   • Fidaxomicin 200 mg twice daily for 10 days (if not used for initial episode) 1, 3
   • Alternative: Vancomycin 125 mg four times daily for 10 days 2, 1
   • Consider bezlotoxumab as adjunctive therapy for patients with high recurrence risk 1, 4

2. Second or subsequent recurrences:

   • Vancomycin in tapered and pulsed regimen (e.g., decreasing daily dose with 125 mg every 3 days) 2
   • OR fidaxomicin 200 mg twice daily for 10 days 1, 3
   • Consider fecal microbiota transplantation (FMT) after appropriate antibiotic lead-in 1, 5, 6

Special Situations

1. When oral therapy is impossible:

   • Metronidazole 500 mg three times daily intravenously 2
   • PLUS intracolonic vancomycin 500 mg in 100 mL saline every 4-12 hours 2, 1
   • AND/OR vancomycin 500 mg four times daily via nasogastric tube 2

2. Surgical indications:

   • Perforation of the colon
   • Systemic inflammation not responding to antibiotic therapy
   • Toxic megacolon or severe ileus
   • Consider surgery before serum lactate exceeds 5.0 mmol/L 2

Important Clinical Considerations

• Avoid antiperistaltic agents and opiates as they can mask symptoms and potentially worsen disease 2
• Fidaxomicin has lower recurrence rates compared to vancomycin and is FDA-approved for patients aged 6 months and older 3, 4
• Metronidazole is no longer recommended as first-line therapy according to recent guidelines 1, 4, 7
• Fecal microbiota transplantation has 70-90% success rates for recurrent CDI and may be considered for refractory cases 1, 5, 6
• Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, can be used as adjunctive therapy to reduce recurrence risk 1, 4

Infection Control Measures

• Use contact precautions for patients with known or suspected CDI
• Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores)
• Environmental cleaning with hypochlorite agents or sporicidal products
• Implement antibiotic stewardship to minimize use of high-risk antibiotics (clindamycin, fluoroquinolones, cephalosporins) 1

Pediatric Considerations

For children ≥ 6 months:

• Weight-based dosing of fidaxomicin oral suspension is FDA-approved 3
• Follow adult recommendations for vancomycin with appropriate dose adjustments

The treatment landscape for CDI has evolved significantly, with vancomycin and fidaxomicin now preferred over metronidazole for initial episodes, and increased recognition of the importance of preventing recurrence through appropriate initial therapy selection.