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 disease severity (non-severe or severe). 1, 2, 3
Initial Episode Treatment
Standard Dosing for All Initial Episodes
- Vancomycin 125 mg orally four times daily for 10 days is the recommended dose for both non-severe and severe initial C. difficile infection 1, 2, 3
- The FDA-approved dose for C. difficile-associated diarrhea is specifically 125 mg administered orally 4 times daily for 10 days 3
- The IDSA/SHEA 2018 guidelines strongly recommend vancomycin or fidaxomicin over metronidazole for initial episodes (strong recommendation, high quality evidence) 1
Disease Severity Definitions
- Non-severe CDI: White blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1, 2
- Severe CDI: White blood cell count ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 1, 2
- Fulminant CDI: Hypotension, shock, ileus, or megacolon 1, 2
Important Caveat About Higher Doses
Do not use higher doses (500 mg four times daily) for routine initial episodes, even if severe. Multiple studies demonstrate no benefit of high-dose vancomycin over the standard 125 mg dose for initial episodes 4, 5, 6. A randomized trial of 46 patients found no significant differences in treatment response between 125 mg and 500 mg four times daily, with similar duration of diarrhea (approximately 4 days) and recurrence rates (20%) 5. A 2019 meta-analysis confirmed no significant reduction in recurrence rates with high-dose versus low-dose vancomycin (OR 2.058,95% CI 0.653-6.489) 6.
Fulminant C. difficile Infection
When to Use Higher Doses
For fulminant CDI only, escalate to vancomycin 500 mg orally four times daily 1, 2, 7
Additional Fulminant CDI Management
- Add intravenous metronidazole 500 mg every 8 hours in addition to oral vancomycin (strong recommendation, moderate quality evidence) 1, 2, 7
- 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, 2
- Consider surgical consultation early—do not wait until the patient is moribund. Operate before serum lactate exceeds 5.0 mmol/L 1, 2
Recurrent C. difficile Infection
First Recurrence
- Vancomycin 125 mg four times daily for 10 days if metronidazole was used for the initial episode 1, 2
- Prolonged tapered and pulsed vancomycin regimen if a standard vancomycin regimen was used initially: 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, 2
- Fidaxomicin 200 mg twice daily for 10 days is an alternative if vancomycin was used initially 1
Second or Subsequent Recurrences
- Vancomycin tapered and pulsed regimen is preferred 1, 2
- Alternative: Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1, 2
- Fecal microbiota transplantation should be considered after multiple recurrences, with success rates exceeding 85% 8
Pediatric Dosing
Non-Severe CDI in Children
Severe or Fulminant CDI in Children
- 10 mg/kg/dose (maximum 500 mg) orally every 8 hours for 10 days 1, 2
- Add intravenous metronidazole for fulminant disease (weak recommendation, low quality evidence) 1
- The total daily pediatric dose should not exceed 2 grams 3
Critical Management Principles
Discontinue Inciting Antibiotics
- Stop the causative antibiotic immediately as this significantly influences recurrence risk (strong recommendation, moderate quality evidence) 1, 2, 7
Avoid Harmful Agents
Monitoring Considerations
- In patients >65 years of age, monitor renal function during and after treatment due to increased nephrotoxicity risk 3
- Patients with inflammatory bowel disease or intestinal mucosal inflammation may have significant systemic vancomycin absorption and require serum concentration monitoring 3