What is the recommended dosage of vancomycin (Vancomycin) for the treatment of Clostridium difficile infection?

Vancomycin Dosing for Clostridium difficile Infection

For initial episodes of C. difficile infection (both non-severe and severe), use vancomycin 125 mg orally four times daily for 10 days; for fulminant disease, increase to 500 mg orally four times daily. 1, 2, 3

Initial Episode Dosing by Disease Severity

Non-Severe CDI (WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL)

• Vancomycin 125 mg orally four times daily for 10 days 1, 2, 3
• This is a strong recommendation with high-quality evidence from the 2018 IDSA/SHEA guidelines 1
• Fidaxomicin 200 mg twice daily for 10 days is an equally acceptable alternative 1, 2

Severe CDI (WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL)

• Vancomycin 125 mg orally four times daily for 10 days 1, 2
• The 2014 European guidelines also support this dosing with Grade A recommendation 1
• Multiple randomized trials demonstrate cure rates of 89-97% with this regimen in severe disease 1
• Do not use higher doses (500 mg four times daily) for routine severe CDI, as randomized trials show no significant improvement in measurable responses compared to the standard 125 mg dose 1

Fulminant CDI (Hypotension, shock, ileus, or megacolon)

• Vancomycin 500 mg orally four times daily 1, 2
• This is a strong recommendation with moderate-quality evidence 1
• If ileus is present, add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as a retention enema 1, 2
• Concurrent intravenous metronidazole 500 mg every 8 hours must be administered, particularly when ileus is present 1, 2

Critical Dosing Considerations

Why 125 mg is Sufficient for Most Cases

• A randomized controlled trial comparing high-dose (500 mg four times daily) versus low-dose (125 mg four times daily) vancomycin found no significant differences in clinical response rates 1
• Retrospective data from 78 patients with severe CDI showed no difference in cure rates (60% vs 64%), time to cure, complication rates, or mortality between high-dose and low-dose vancomycin 4
• A 2019 meta-analysis of 137 patients confirmed no significant reduction in recurrence rates with high-dose versus low-dose vancomycin (OR 2.058,95% CI: 0.653-6.489) 5

When Higher Doses May Be Considered

• There is a trend toward lower recurrence rates with higher vancomycin doses (12% vs 1.9%, p=0.09), though this did not reach statistical significance 4
• For multiple recurrent CDI, some experts recommend vancomycin 500 mg four times daily for 10 days, though this has only Grade C recommendation 1

Recurrent CDI Dosing

First Recurrence

• Vancomycin 125 mg four times daily for 10 days if metronidazole was used initially 1, 2
• Prolonged tapered and pulsed vancomycin regimen if standard vancomycin was used initially: 125 mg four times daily for 10-14 days, then twice daily for one week, once daily for one week, then every 2-3 days for 2-8 weeks 1, 2
• Fidaxomicin 200 mg twice daily for 10 days is an alternative 1, 2

Multiple Recurrences (≥2 recurrences)

• Vancomycin 125 mg four times daily for 10 days, followed by pulse regimen (125-500 mg/day every 2-3 days) for at least 3 weeks 1
• Alternative: Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Fecal microbiota transplantation should be considered after multiple recurrences 1, 2

Special Situations

When Oral Administration is Not Possible

• Intravenous metronidazole 500 mg three times daily for 10 days for non-severe disease when oral route unavailable 1
• For severe disease with ileus: IV metronidazole 500 mg three times daily PLUS vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or rectal enema 1

Systemic Absorption Concerns

• Oral vancomycin at 125 mg four times daily is not systemically absorbed in 98% of patients, even with severe CDI or renal failure 6
• However, clinically significant serum concentrations can occur in patients with inflammatory intestinal mucosa 3
• Monitor serum vancomycin levels in patients with renal insufficiency, severe colitis, or those receiving concurrent aminoglycosides 3

Common Pitfalls to Avoid

• Do not routinely use 500 mg four times daily for non-fulminant severe CDI - evidence shows no benefit over 125 mg dosing 1, 4, 5
• Do not use metronidazole as first-line therapy - it has lower cure rates in severe disease (76% vs 97% with vancomycin) and risk of cumulative neurotoxicity 1
• Do not administer vancomycin intravenously for CDI treatment - parenteral vancomycin is not effective for CDI as it is not excreted into the colon 3
• Always discontinue the inciting antibiotic as soon as possible - this significantly influences recurrence risk 1, 2

Monitoring in High-Risk Patients

• Patients >65 years of age have increased risk of nephrotoxicity with oral vancomycin 3
• Monitor renal function during and after treatment in elderly patients, even those with normal baseline renal function 3
• Treatment duration may be extended to 14 days if clinical response is delayed 2