What is the recommended treatment for Clostridium difficile (C. difficile) infection?

Treatment of Clostridium difficile Infection

For initial episodes of C. difficile infection (CDI), either vancomycin 125 mg orally four times daily or fidaxomicin 200 mg orally twice daily for 10 days is recommended over metronidazole as first-line therapy. 1, 2

Treatment Algorithm Based on Disease Severity

Initial Episode Classification and Treatment

Non-severe CDI (Adults)

• Definition: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 1, 2
• Treatment:
  • Vancomycin 125 mg orally four times daily for 10 days 1, 3
  • OR Fidaxomicin 200 mg orally twice daily for 10 days 1, 4
  • Discontinue the inciting antibiotic as soon as possible 1, 2

Severe CDI (Adults)

• Definition: WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 1, 2
• Treatment:
  • Vancomycin 125 mg orally four times daily for 10 days 1
  • OR Fidaxomicin 200 mg orally twice daily for 10 days 1, 4

Fulminant CDI (Adults)

• Definition: Hypotension, shock, ileus, or megacolon 1
• Treatment:
  • Vancomycin 500 mg orally four times daily 1, 2
  • PLUS intravenous metronidazole 500 mg every 8 hours 1
  • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1, 2

Pediatric Treatment (6 months to <18 years)

Non-severe CDI

• Treatment:
  • Vancomycin 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days 1, 2
  • OR Metronidazole 7.5 mg/kg/dose (maximum 500 mg) orally three or four times daily for 10 days 1

Severe/Fulminant CDI

• Treatment:
  • Vancomycin 10 mg/kg/dose (maximum 500 mg) orally four times daily for 10 days 1
  • Consider adding intravenous metronidazole if critically ill 1

Management of Recurrent CDI

First Recurrence

• If metronidazole was used for initial episode:

  • Vancomycin 125 mg orally four times daily for 10 days 1, 2

• If standard vancomycin was used for initial episode:

  • Tapered and pulsed vancomycin regimen (e.g., 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks) 1, 2
  • OR Fidaxomicin 200 mg orally twice daily for 10 days 1, 5

Second or Subsequent Recurrence

• Options include:
  • Vancomycin in a tapered and pulsed regimen 1, 2
  • Vancomycin 125 mg four times daily for 10 days, followed by rifaximin 400 mg three times daily for 20 days 1
  • Fidaxomicin 200 mg twice daily for 10 days 1
  • Fecal microbiota transplantation (after failing appropriate antibiotic treatments) 1, 2

Monitoring Treatment Response

• Expect decreased stool frequency and improved consistency within 3 days of starting treatment 2
• If no improvement after 3-5 days, reassess severity and consider alternative diagnoses 2

Important Considerations and Pitfalls

• Avoid metronidazole for severe CDI: Despite its lower cost, metronidazole is less effective than vancomycin for severe cases and should be reserved only for non-severe cases when access to vancomycin/fidaxomicin is limited 1

• Discontinue inciting antibiotics: Failure to stop the triggering antibiotic significantly increases recurrence risk 1, 2

• Avoid antiperistaltic agents: These can mask symptoms and potentially worsen disease 2

• Dosing controversy: While some studies have examined higher doses of vancomycin for severe CDI, current evidence does not support routine use of doses higher than those recommended in guidelines 6, 7, 8

• Recurrence prevention: Fidaxomicin has shown superiority in preventing recurrence compared to vancomycin (19.7% vs 35.5% recurrence rates) 5

• Surgical consultation: Early surgical evaluation is recommended for patients with perforation, systemic inflammation not responding to antibiotics, toxic megacolon, severe ileus, or serum lactate >5.0 mmol/L 2

• Vancomycin absorption: While oral vancomycin is minimally absorbed, patients with inflammatory bowel disorders may have significant systemic absorption, requiring monitoring in those with renal insufficiency 3