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

Treatment of Clostridioides difficile Infection (C-diff)

For C-diff infection, first-line treatment should be oral vancomycin 125 mg four times daily for 10 days for both non-severe and severe cases, with metronidazole as an alternative for non-severe cases only. 1

Disease Severity Classification

• C-diff infection should be classified as non-severe or severe to guide appropriate treatment 1
• Non-severe CDI is characterized by stool frequency <4 times daily and no signs of severe colitis 2, 1
• Severe CDI is defined by one or more of: temperature >38.5°C, hemodynamic instability, leukocyte count >15×10⁹/L, serum creatinine rise >50% above baseline, elevated serum lactate, pseudomembranous colitis on endoscopy, or colonic wall thickening on imaging 2, 1

First-Line Treatment Algorithm

Non-Severe CDI:

• First choice: Vancomycin 125 mg four times daily orally for 10 days 1
• Alternative: Metronidazole 500 mg three times daily orally for 10 days 2
• For mild CDI clearly induced by antibiotics, consider stopping the inducing antibiotic and observing closely for clinical deterioration 2, 1

Severe CDI:

• First choice: Vancomycin 125 mg four times daily orally for 10 days 2, 1
• Alternative: Fidaxomicin 200 mg twice daily orally for 10 days, especially for patients at high risk of recurrence 1, 3
• If oral therapy is impossible: Metronidazole 500 mg three times daily intravenously PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 2

Treatment of Recurrent CDI

• First recurrence: Treat based on severity as above 1
• Second or subsequent recurrences:
  • Vancomycin 125 mg four times daily orally for at least 10 days 2
  • Consider a tapered and pulsed vancomycin regimen (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 2, 1
  • Fidaxomicin 200 mg twice daily orally for 10 days may be considered 1, 3
  • Fecal microbiota transplantation for multiple recurrences that have failed appropriate antibiotic treatments 1, 4

Surgical Management

• Colectomy should be performed in the following situations 2:
  • Perforation of the colon
  • Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
  • Toxic megacolon or severe ileus
• Surgery should be performed before serum lactate exceeds 5.0 mmol/L 2

Special Considerations and Pitfalls

• Antiperistaltic agents and opiates should be avoided as they may worsen symptoms and outcomes 2
• Discontinue the inciting antibiotic if possible to reduce risk of treatment failure 1
• Hand hygiene with soap and water is required, as alcohol-based hand sanitizers are ineffective against C. difficile spores 1
• Discontinue unnecessary proton pump inhibitors in patients at high risk for CDI 1
• Metronidazole is significantly less expensive than vancomycin and fidaxomicin, which may influence treatment decisions in resource-limited settings 5
• Recent evidence shows vancomycin is superior to metronidazole for achieving symptomatic cure (79% vs 72%) 5
• Fidaxomicin has been shown to be more effective than vancomycin for achieving symptomatic cure (71% vs 61%) 5

Pediatric Considerations

• For children 6 months and older, fidaxomicin is FDA-approved with weight-based dosing 3:
  • 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 or one 200 mg tablet twice daily