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

Oral Vancomycin Dosing for C. difficile Infection

For initial C. difficile infection, use vancomycin 125 mg orally four times daily for 10 days, regardless of disease severity (non-severe, severe, or fulminant). 1, 2, 3, 4

Initial Episode Treatment

Standard Dosing for All Severities

• Vancomycin 125 mg orally four times daily for 10 days is the recommended dose for both non-severe and severe initial CDI. 1, 2, 3, 4
• The 2018 IDSA/SHEA guidelines strongly recommend vancomycin or fidaxomicin over metronidazole for all initial episodes (strong recommendation, high quality evidence). 1, 3
• The FDA-approved dose for C. difficile-associated diarrhea is 125 mg administered orally 4 times daily for 10 days. 4

Higher Doses Are NOT Beneficial for Routine Cases

• Do not use higher doses (500 mg four times daily) for routine severe CDI—no clinical benefit has been demonstrated and it may unnecessarily disrupt colonic flora. 2
• European guidelines give a Grade A recommendation with Level I evidence that 500 mg four times daily shows no significant benefit over standard 125 mg dosing for severe CDI. 2
• A retrospective study of 78 patients with severe CDI found no difference in cure rates (60% vs 64%, P=0.76), time to cure, complications, or mortality between high-dose (>500 mg daily) and low-dose (≤500 mg daily) vancomycin. 5

Fulminant CDI Exception

• For fulminant CDI (hypotension/shock, ileus, or megacolon), escalate to vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg every 8 hours. 1, 3
• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as a retention enema (weak recommendation, low quality evidence). 1, 6, 3
• Consider early surgical consultation—do not wait until the patient is moribund. 3

Recurrent CDI Treatment

First Recurrence

• If metronidazole was used initially, treat with vancomycin 125 mg four times daily for 10 days. 3
• If standard vancomycin was used initially, use a 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. 3

Multiple Recurrences (≥2 relapses)

• Vancomycin 125 mg four times daily for 10 days, followed by either:
  • Pulse regimen: 125-500 mg/day every 2-3 days for at least 3 weeks (Grade B recommendation), OR 1, 2
  • Taper regimen: gradually decreasing the dose to 125 mg per day (Grade B recommendation). 1, 2
• Alternative: Fidaxomicin 200 mg twice daily for 10 days shows lower recurrence rates after first recurrence (Grade B recommendation). 1, 2, 7
• For patients who fail FMT or cannot access it, prolonged vancomycin 125 mg once daily as secondary prophylaxis is effective—in one series, only 1 relapse occurred during 200 patient-months of follow-up. 8

Pediatric Dosing

• For non-severe CDI: 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days. 3, 4
• For severe/fulminant CDI: 10 mg/kg/dose (maximum 500 mg) orally every 8 hours for 10 days. 3
• The usual daily dosage is 40 mg/kg in 3 or 4 divided doses for 7-10 days, not to exceed 2 g daily. 4

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic immediately—this significantly influences recurrence risk (strong recommendation, moderate quality evidence). 1, 3

Avoid Harmful Agents

• Never use antiperistaltic agents or opiates—they mask symptoms, worsen outcomes, and increase complications. 2, 3

Route of Administration Matters

• Parenteral (IV) vancomycin is completely ineffective for CDI and should never be used. 3, 4
• Oral vancomycin must be given for CDI treatment—it is not systemically absorbed in most patients. 4, 9
• In a prospective study of 57 patients, 98% had no detectable serum vancomycin concentrations after oral administration of 125 mg four times daily. 9

Special Monitoring Considerations

Systemic Absorption Risk

• Clinically significant serum concentrations can occur in patients with inflammatory disorders of the intestinal mucosa or active C. difficile colitis. 4
• Monitor serum vancomycin concentrations in patients with renal insufficiency, colitis, or those receiving concomitant aminoglycosides. 4

Nephrotoxicity Risk

• Nephrotoxicity can occur during or after oral vancomycin therapy, with increased risk in patients >65 years of age. 4
• Monitor renal function during and after treatment in elderly patients, even those with normal baseline renal function. 4

Common Pitfalls to Avoid

• Do not order "test of cure" after CDI treatment—treatment response typically requires 3-5 days after starting therapy. 2
• Do not use higher doses routinely—the standard 125 mg dose yields fecal concentrations 500-1000 times the C. difficile MIC, making higher doses unnecessary in most cases. 2
• Do not use oral vancomycin for other infections—it is not effective for systemic infections and is only indicated for CDI and staphylococcal enterocolitis. 4