Oral Vancomycin is the Recommended Treatment for Clostridium difficile Infection
For Clostridium difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days is the recommended treatment for initial episodes of severe CDI, while either metronidazole or vancomycin can be used for non-severe cases. 1, 2
Treatment Based on Disease Severity
Non-Severe CDI
- Initial episode: Either metronidazole 500 mg three times daily orally for 10 days OR vancomycin 125 mg four times daily orally for 10 days 1, 2
- First recurrence: Same as initial episode based on severity 1, 2
- Pediatric dosing for non-severe CDI: Metronidazole 7.5 mg/kg/dose three or four times daily (maximum 500 mg per dose) OR vancomycin 10 mg/kg/dose four times daily (maximum 125 mg per dose) for 10 days 1
Severe CDI
- Initial episode: Vancomycin 125 mg four times daily orally for 10 days 1, 2
- Standard 125 mg dose yields fecal concentrations 500-1000 times the C. difficile MIC, making higher doses unnecessary in most cases 2, 3
- Pediatric dosing for severe CDI: Vancomycin 10 mg/kg/dose four times daily (maximum 500 mg per dose) orally for 10 days 1
Fulminant CDI (with ileus or toxic megacolon)
- Vancomycin 500 mg four times daily orally or via nasogastric tube AND metronidazole 500 mg three times daily intravenously 1
- Consider adding intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours as a retention enema when ileus is present 1, 4
Treatment for Multiple Recurrences
- Second or subsequent recurrence: Vancomycin in a tapered and pulsed regimen 1, 2
- Tapered regimen example: Vancomycin 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
- Alternative options include vancomycin for 10 days followed by rifaximin for 20 days or fidaxomicin 200 mg twice daily for 10 days 1, 2
- For multiple recurrences not responding to antibiotic therapy, fecal microbiota transplantation is recommended 1, 2
Administration Considerations
- Oral vancomycin is poorly absorbed from the gastrointestinal tract, with 98% of patients showing no detectable serum levels when given 125 mg four times daily 5
- Vancomycin capsules are FDA-approved for CDI at a dose of 125 mg four times daily for 10 days in adults 6
- For pediatric patients, the FDA-approved dosage is 40 mg/kg/day in 3-4 divided doses for 7-10 days, not to exceed 2 g daily 6
Clinical Pearls and Pitfalls
- Treatment response typically requires 3-5 days after starting therapy 2, 7
- "Test of cure" is not recommended after CDI treatment 2
- Avoid antiperistaltic agents and opiates as they may mask symptoms and potentially worsen the disease 1, 2
- One study showed that patients with ≥4 stools daily had lower fecal vancomycin levels than those with fewer stools, suggesting a potential benefit of higher initial dosing (250-500 mg) during the first 24-48 hours in patients with severe diarrhea 3
- While some studies suggest potential benefits of high-dose vancomycin (500 mg four times daily) in reducing recurrence rates or improving outcomes in non-responsive cases 8, standard guidelines still recommend 125 mg four times daily for most cases of CDI 1, 2