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

Vancomycin Dosing for C. difficile Infection

For an initial episode of C. difficile infection, use vancomycin 125 mg orally four times daily for 10 days, regardless of whether the disease is classified as non-severe or severe. 1, 2

Initial Episode Treatment

The IDSA/SHEA guidelines strongly recommend vancomycin or fidaxomicin over metronidazole for all initial episodes of C. difficile infection 1. The standard dose is:

• Vancomycin 125 mg orally four times daily for 10 days 1, 2
• This same dose applies to both non-severe disease (WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL) and severe disease (WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL) 1
• The FDA label confirms 125 mg four times daily for 10 days as the approved dose for C. difficile-associated diarrhea 2

Critical point: Higher doses (e.g., 250 mg or 500 mg four times daily) for non-fulminant severe disease do not improve outcomes. A 2013 study found no difference in cure rates, time to cure, complications, or mortality between high-dose (>500 mg daily) and low-dose (≤500 mg daily) vancomycin for severe CDI 3.

Fulminant C. difficile Infection

For fulminant disease (hypotension, shock, ileus, or megacolon), escalate therapy:

• Vancomycin 500 mg orally four times daily 1
• Add IV metronidazole 500 mg every 8 hours in addition to oral vancomycin 1
• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as a retention enema 1
• Obtain early surgical consultation—do not delay until the patient deteriorates 1

Recurrent C. difficile Infection

For first recurrence:

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

Important caveat: Recent animal model data suggests that pulse dosing every 2-3 days does not facilitate clearance of C. difficile spores, as vegetative growth occurs between doses when vancomycin levels become undetectable 4. However, the tapered/pulsed regimen remains guideline-recommended for recurrent disease 1.

Pediatric Dosing

• Non-severe CDI: 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days 1
• Severe/fulminant CDI: 10 mg/kg/dose (maximum 500 mg) orally every 8 hours for 10 days 1
• The FDA label states the usual pediatric dose is 40 mg/kg/day in 3-4 divided doses, not to exceed 2 g daily 2

Critical Management Principles

• Discontinue the inciting antibiotic immediately—this significantly reduces recurrence risk 1
• Never use IV vancomycin for C. difficile infection—it is completely ineffective as vancomycin must reach the colonic lumen 1, 2
• Avoid antiperistaltic agents and opiates entirely—they worsen outcomes and increase complications 1
• Monitor for nephrotoxicity, especially in patients >65 years of age, as oral vancomycin can achieve clinically significant serum concentrations in patients with inflammatory intestinal mucosa 2

Common Pitfalls

• Do not use higher vancomycin doses (250 mg or 500 mg four times daily) for routine severe disease—reserve 500 mg dosing only for fulminant cases 1
• Do not use metronidazole as first-line therapy for initial episodes, even if non-severe 1, 5
• Oral vancomycin does not increase the risk of vancomycin-resistant enterococci (VRE) compared to metronidazole 6