Oral Vancomycin Dosing for Clostridioides difficile Infection

For initial C. difficile infection, administer oral vancomycin 125 mg four times daily for 10 days, regardless of disease severity. 1

Initial Episode Dosing

Oral vancomycin 125 mg four times daily for 10 days is the FDA-approved dose for C. difficile-associated diarrhea 1
This standard 125 mg dose achieves fecal concentrations 500-1000 times the C. difficile MIC, making higher doses unnecessary in most cases 2
For severe CDI specifically, European guidelines give this regimen a Grade A recommendation with Level I evidence 3

Higher doses (500 mg four times daily) show no significant benefit over standard dosing for severe CDI 3, 4
A randomized controlled trial found no significant differences in cure rates between high-dose and low-dose vancomycin regimens, though results were not stratified by severity 3
Retrospective data from 78 patients with severe CDI showed no difference in cure rates (60% vs 64%), time to cure, complications, or mortality between high-dose (>500 mg daily) and low-dose (≤500 mg daily) vancomycin 4
There was a trend toward lower recurrence rates with higher doses (1.9% vs 12%), but this did not reach statistical significance 4

Repeat the initial treatment regimen: vancomycin 125 mg four times daily for 10 days 2

Vancomycin 125 mg four times daily for 10 days, followed by a pulse regimen (125-500 mg/day every 2-3 days) for at least 3 weeks (Grade B recommendation) 3
Alternative: Vancomycin 125 mg four times daily for 10 days, followed by taper regimen: gradually decreasing the dose to 125 mg per day (Grade B recommendation) 3
Fidaxomicin 200 mg twice daily for 10 days is an alternative with lower recurrence rates after first recurrence 3

Oral vancomycin 500 mg four times daily PLUS vancomycin retention enema 500 mg in 100 mL normal saline every 6 hours PLUS intravenous metronidazole 500 mg every 8 hours 5, 2
The higher oral dose (500 mg) is specifically recommended for fulminant disease when combined with rectal administration 5
Rectal vancomycin is critical when ileus impairs oral drug delivery to the colon 5

Fecal vancomycin levels are proportional to dose administered and remain 3 orders of magnitude higher than the MIC90 even with standard dosing 6
Patients with ≥4 stools daily may have lower fecal vancomycin levels than those with less frequent diarrhea 6
One study found patients receiving 125 mg four times daily had levels below 50 mg/L during the first day of treatment, suggesting a potential role for loading doses 6

Oral vancomycin is not systemically absorbed in 98% of patients receiving standard doses 7
However, clinically significant serum concentrations can occur in patients with inflammatory intestinal mucosa or renal insufficiency 1
Monitor serum vancomycin concentrations in patients >65 years, those with renal insufficiency, disrupted intestinal integrity, or receiving concomitant aminoglycosides 5, 1

Avoid using higher doses (>125 mg four times daily) for routine severe CDI, as no clinical benefit has been demonstrated and it may cause unnecessary disruption to colonic flora 3, 4, 6
Do not use antiperistaltic agents or opiates, as they may mask symptoms and worsen disease 2
Remember that oral vancomycin is only for C. difficile colitis and staphylococcal enterocolitis—it is not effective for other infections and is not systemically absorbed for treating other conditions 1
For patients unable to take oral medications or with ileus, rectal vancomycin administration is essential, though it is unclear whether sufficient drug reaches beyond the left colon 5