What are the recommended antibiotics for treating pseudo-membranous colitis caused by Clostridioides difficile?

Treatment of Pseudomembranous Colitis Caused by Clostridioides difficile

For pseudomembranous colitis caused by Clostridioides difficile, oral vancomycin 125 mg four times daily for 10 days is the first-line treatment, with fidaxomicin 200 mg twice daily for 10 days as an effective alternative. 1, 2

First-Line Treatment Options

Non-Severe CDI

• Oral vancomycin: 125 mg four times daily for 10 days 2, 1, 3
• Fidaxomicin: 200 mg twice daily for 10 days 2, 1

Note: While metronidazole (500 mg orally three times daily for 10 days) was historically used, recent guidelines no longer recommend it as first-line therapy due to lower efficacy compared to vancomycin and fidaxomicin 2, 1

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

For severe CDI:

• Oral vancomycin: 125 mg four times daily for 10 days 2
  • Consider increasing to 500 mg four times daily 2
• Fidaxomicin: 200 mg twice daily for 10 days 2, 4

Important: The use of oral metronidazole in severe CDI is strongly discouraged 2

Fulminant CDI (with hypotension, shock, ileus, or megacolon)

• Vancomycin: 500 mg four times daily (orally, via nasogastric tube, or rectally) 2, 1
• If ileus present: Add rectal vancomycin (500 mg in 100 ml as retention enema, 4 times daily) 2
• Consider adding IV metronidazole 500 mg three times daily 1
• Surgical consultation for possible colectomy if:
  • Perforation
  • Systemic inflammation not responding to antibiotics
  • Toxic megacolon
  • Severe ileus
  • Serum lactate >5.0 mmol/L 2

Treatment of Recurrent CDI

First Recurrence

• If metronidazole was used initially: Vancomycin 125 mg orally four times daily for 10 days 2
• If vancomycin was used initially:
  • Fidaxomicin 200 mg twice daily for 10 days 2, 1, OR
  • Prolonged tapered and pulsed vancomycin regimen (e.g., 125 mg 4 times daily for 10-14 days, then 2 times daily for a week, then once daily for a week, then every 2-3 days for 2-8 weeks) 2, 1

Second and Subsequent Recurrences

• Vancomycin in a tapered and pulsed regimen 2, 1, OR
• Vancomycin 125 mg orally 4 times for 10 days followed by rifaximin 400 mg 3 times daily for 20 days 2, OR
• Fidaxomicin 200 mg twice daily for 10 days 2, OR
• Fecal microbiota transplantation (FMT) 2, 5

Important Clinical Considerations

1. Route of administration: Vancomycin must be given orally for CDI treatment as parenteral administration is not effective for intestinal infections 3

2. Monitoring response: Evaluate treatment response after at least 3 days of therapy. Complete normalization of bowel habits may take several weeks despite clinical cure 1

3. Discontinue inciting antibiotics if possible to reduce recurrence risk 1

4. Avoid antiperistaltic agents and opiates to prevent worsening of disease 1

5. Efficacy of lower vancomycin dose: Studies have shown that 125 mg of vancomycin four times daily is as effective as 500 mg four times daily, with the lower dose being more cost-effective 6

6. Fidaxomicin advantages: Lower recurrence rates compared to vancomycin (6.8% vs 17.6%) and longer time to recurrence 4

7. FMT consideration: For multiple recurrent CDI unresponsive to repeated antibiotic treatment, FMT in combination with oral antibiotic treatment is strongly recommended, with success rates of 70-90% 2, 5

Special Populations

• Pediatric patients: Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 1

  • Fidaxomicin is FDA-approved for pediatric patients ≥6 months of age 1

• Elderly patients (>65 years): Monitor renal function during and after treatment with vancomycin due to increased risk of nephrotoxicity 3