What is the recommended dose of vancomycin (Vancomycin) for treating Clostridioides difficile (C. diff) infection?

Vancomycin Dosing for C. difficile Infection

For C. difficile infection (CDI), the recommended dose 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, 2

Disease Severity Assessment

Proper dosing depends on disease severity classification:

• Non-severe CDI:

  • WBC ≤15,000 cells/mL
  • Serum creatinine <1.5 mg/dL
  • Stool frequency <4 times daily
  • No signs of severe colitis

• Severe CDI:

  • WBC ≥15,000 cells/mL OR
  • Serum creatinine >1.5 mg/dL (or >50% above baseline)
  • Signs of severe colitis on imaging or endoscopy

• Fulminant CDI:

  • Hypotension
  • Shock
  • Ileus
  • Megacolon

Specific Dosing Recommendations

Initial Episode Treatment

• Non-severe CDI:

  • Vancomycin 125 mg orally four times daily for 10 days 3, 1, 2
  • FDA-approved standard dosage 2

• Severe CDI:

  • Vancomycin 500 mg orally four times daily for 10 days 1
  • Note: The older ESCMID guidelines recommended 125 mg four times daily even for severe cases 3, but more recent guidance supports higher dosing for severe cases 1

• Fulminant CDI with Ileus:

  • Vancomycin 500 mg orally four times daily PLUS
  • Consider adding rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1

Recurrent CDI Treatment

• First Recurrence:

  • Same as initial episode based on severity 3

• Second or Later Recurrence:

  • Vancomycin 125 mg four times daily for at least 10 days 3
  • Consider tapered and pulsed regimen (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 3, 1

Important Clinical Considerations

• Early Treatment: Begin appropriate therapy immediately upon diagnosis to reduce mortality risk.

• Discontinue Inciting Antibiotics: If possible, stop the antibiotic that triggered the CDI to improve outcomes 1.

• Avoid Antiperistaltic Agents: These can mask symptoms and potentially worsen disease 3, 1.

• Monitor Treatment Response: Expect decreased stool frequency and improved consistency within 3 days of starting treatment 3, 1.

• Pediatric Dosing: For children, the dose is 10 mg/kg/dose (maximum 125 mg for non-severe or 500 mg for severe) four times daily for 10 days 1.

• Loading Dose Consideration: Some evidence suggests using a higher loading dose (250 mg or 500 mg) during the first 24-48 hours might be beneficial to achieve adequate fecal concentrations quickly, especially in patients with frequent stools 4.

Evidence Quality and Controversies

While older studies suggested no difference between 125 mg and 500 mg dosing regimens 5, more recent guidelines differentiate dosing based on disease severity 1. The higher dose (500 mg four times daily) is now recommended for severe/fulminant cases despite limited comparative evidence 6.

Faecal vancomycin concentrations are proportional to the oral dose and remain well above the MIC90 for C. difficile even with increased stool frequency 4. However, during the first day of treatment with the standard 125 mg dose, some patients might have suboptimal fecal levels 4.