What is the recommended dosage of vancomycin for treating Clostridium difficile (C. diff) infection?

Vancomycin Dosage for Clostridium difficile Infection

For Clostridium difficile infection (CDI), the recommended dosage of oral vancomycin is 125 mg four times daily for 10 days for non-severe cases, and 500 mg four times daily for 10 days for severe or fulminant cases. 1

Disease Severity Classification and Appropriate Dosing

Non-severe CDI

• Definition: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL
• Recommended treatment:
  • Vancomycin 125 mg orally four times daily for 10 days 1, 2
  • Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1

Severe CDI

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

Fulminant CDI

• Definition: Hypotension, shock, ileus, or megacolon
• Recommended treatment:
  • Vancomycin 500 mg orally four times daily for 10 days 1, 3
  • If ileus present: Add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as a retention enema 1
  • Plus intravenous metronidazole 500 mg every 8 hours 1

Special Considerations

For Recurrent CDI

1. First recurrence:

   • If metronidazole was used initially: Vancomycin 125 mg orally four times daily for 10 days 1
   • If standard vancomycin was used initially: Consider tapered and pulsed vancomycin regimen 1

2. Second or subsequent recurrences:

   • Vancomycin in a tapered and pulsed 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, 3
   • Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

Important Clinical Considerations

• Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1
• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 3
• Monitor treatment response within 3 days (decreased stool frequency and improved consistency) 3

Evidence Analysis

Recent research suggests that higher doses of vancomycin (>500 mg daily) compared to lower doses (≤500 mg daily) do not significantly improve cure rates for severe CDI (60% vs. 64%, p=0.76) 4. However, there was a trend toward lower recurrence rates with higher doses (1.9% vs. 12%, p=0.09) 4.

For patients with multiple recurrences who have failed or don't have access to fecal microbiota transplantation, prolonged vancomycin at 125 mg once daily has shown effectiveness as secondary prophylaxis 5, 6.

Pediatric Dosing

For pediatric patients with CDI, the recommended dosage is 40 mg/kg/day divided into 3-4 doses (not to exceed 2 g/day) for 7-10 days 2.

Common Pitfalls to Avoid

1. Using oral vancomycin for non-C. difficile infections (not effective for other types of infections) 2
2. Failing to adjust therapy based on disease severity
3. Not considering rectal vancomycin administration in patients with ileus
4. Using inadequate volume for rectal vancomycin (research suggests 500 mL is more effective than 100 mL) 7
5. Not monitoring for nephrotoxicity, especially in patients >65 years of age 2

Remember that vancomycin is not systemically absorbed when given orally, but significant serum concentrations have been reported in patients with inflammatory disorders of the intestinal mucosa, potentially leading to adverse effects 2.