What is the treatment for Clostridioides difficile infection (CDI)?

Treatment of Clostridioides difficile Infection (CDI)

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

Disease Severity Classification

• CDI severity should be classified as non-severe or severe to guide appropriate treatment 2
• Non-severe CDI is characterized by:
  • Stool frequency <4 times daily 1
  • No signs of severe colitis 1
• Severe CDI is defined by the presence of one or more of:
  • Temperature >38.5°C 2
  • Hemodynamic instability 2
  • Leukocyte count >15×10⁹/L 1
  • Serum creatinine rise >50% above baseline 1
  • Elevated serum lactate 1
  • Pseudomembranous colitis on endoscopy 1
  • Colonic wall thickening on imaging 1

Treatment Algorithm for Initial CDI Episode

Non-severe CDI:

• First choice: Vancomycin 125 mg four times daily orally for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg twice daily orally for 10 days 1, 3
• If access to vancomycin/fidaxomicin is limited: Metronidazole 500 mg three times daily orally for 10 days 1
  • Note: Avoid repeated or prolonged courses of metronidazole due to risk of cumulative neurotoxicity 1

Severe CDI:

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

When oral therapy is not possible:

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

Special Considerations

• Discontinue the inciting antibiotic as soon as possible to improve clinical response and decrease recurrence rates 1
• Mild CDI (stool frequency <4 times daily, no signs of severe colitis) clearly induced by antibiotics may be treated by stopping the inducing antibiotic with close observation 1
• Avoid antiperistaltic agents and opiates as they may mask symptoms and potentially worsen outcomes 1
• Empiric antibiotic therapy should be started if substantial delay in laboratory confirmation is expected or for fulminant CDI 1

Treatment of Recurrent CDI

First Recurrence:

• Treat as an initial episode based on severity classification 1

Second and Subsequent Recurrences:

• If oral therapy is possible: Vancomycin 125 mg four times daily orally for at least 10 days, followed by a tapered and pulsed regimen 1, 2
  • Example taper: Decreasing daily dose with 125 mg every 3 days 1
  • Example pulse: Dose of 125 mg every 3 days for 3 weeks 1
• If oral therapy is impossible: Metronidazole 500 mg three times daily intravenously for 10-14 days PLUS retention enema of vancomycin 500 mg in 100 mL normal saline every 4-12 hours AND/OR vancomycin 500 mg four times daily by nasogastric tube 1
• Consider: Fecal microbiota transplantation for multiple recurrences that have failed appropriate antibiotic treatments 2, 4

Surgical Management

• Colectomy should be performed in the following situations:
  • Perforation of the colon 1
  • Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy 1
  • Toxic megacolon 1
  • Severe ileus 1
• Surgery should be performed before colitis becomes very severe, preferably before serum lactate exceeds 5.0 mmol/L 1

Important Caveats and Pitfalls

• Recent studies have shown that metronidazole is inferior to vancomycin for clinical cure in patients with CDI, leading to the shift in first-line recommendations 1, 5
• Fidaxomicin has been associated with lower recurrence rates compared to vancomycin, making it particularly valuable for patients at high risk of recurrence 6, 7
• The standard treatment duration is 10 days, but some patients may have delayed response to treatment, particularly with metronidazole 1
• Discontinue unnecessary proton pump inhibitors in patients at high risk for CDI 2
• Hand hygiene with soap and water (not alcohol-based sanitizers) is required for infection control as alcohol is ineffective against C. difficile spores 2