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

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of C. difficile infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are recommended as first-line treatments, with fidaxomicin being preferred due to lower recurrence rates. 1

Treatment Based on Disease Severity

Non-severe CDI

• First-line options:

  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Vancomycin 125 mg orally four times daily for 10 days 1, 3

• Important note: Metronidazole is no longer recommended as first-line therapy for adults 4, despite earlier guidelines suggesting its use for non-severe disease 3

Severe CDI

Severe CDI is defined by:

• Temperature >38.5°C
• Leukocytosis >15,000/mm³
• Serum creatinine rise >50% above baseline
• Pseudomembranous colitis on endoscopy
• Signs of severe colitis on imaging 1

Treatment for severe CDI:

• Vancomycin 125-500 mg orally four times daily for 10 days 1
• For fulminant cases: Vancomycin 500 mg four times daily (orally, via nasogastric tube, or rectally) PLUS metronidazole 500 mg IV three times daily 1

Fulminant CDI with Complications

For patients with:

• Perforation
• Systemic inflammation
• Toxic megacolon
• Severe ileus
• Serum lactate >5.0 mmol/L

Management:

• Immediate surgical consultation for possible colectomy 3, 1
• Alternative surgical approach: diverting loop ileostomy with colonic lavage, combined with antibiotic treatment (intracolonic antegrade vancomycin and intravenous metronidazole) 3

Treatment of Recurrent CDI

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days 1
• OR vancomycin in a tapered and pulsed regimen 1

Multiple Recurrences (≥2)

• Vancomycin 125 mg four times daily for 10 days followed by either:
  • Pulse regimen (125-500 mg/day every 2-3 days) for at least 3 weeks, or
  • Tapered regimen: gradually decreasing the dose to 125 mg per day 1
• Fecal microbiota transplantation (FMT) after appropriate antibiotic treatments have failed 1, 5
  • FMT has shown 70-90% success rates in patients with multiple recurrent CDI 1, 5
• Consider bezlotoxumab 10 mg/kg IV once during antibiotic treatment for patients at high risk of recurrence 1

Pediatric Dosing

• For children ≥6 months of age:
  • Fidaxomicin is FDA-approved 1, 2
  • Weight-based dosing for oral suspension 2:
    • 4 kg to <7 kg: 80 mg (2 mL) twice daily
    • 7 kg to <9 kg: 120 mg (3 mL) twice daily
    • 9 kg to <12.5 kg: 160 mg (4 mL) twice daily
    • ≥12.5 kg: 200 mg (5 mL) twice daily
  • Alternative: Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 1

Important Clinical Considerations

• Stop inciting antibiotics as soon as possible to reduce recurrence risk 1
• Avoid antiperistaltic agents and opiates to prevent worsening of disease 1
• Evaluate treatment response after at least 3 days of therapy 1
• Complete normalization of bowel habits may take several weeks despite clinical cure 1
• Fidaxomicin has been shown to have lower recurrence rates compared to vancomycin (15.4% vs. 25.3%) 6
• High-dose vancomycin (500 mg four times daily) has not shown superior efficacy compared to standard dose (125 mg four times daily) 7

Common Treatment Pitfalls to Avoid

• Using metronidazole as first-line therapy for severe CDI
• Failure to recognize fulminant CDI requiring urgent intervention
• Overuse of FMT before trying appropriate antibiotic regimens
• Not screening FMT donors properly for transmissible pathogens
• Inadequate duration of therapy 1