What dose of vancomycin should I increase to for a patient with persistent Clostridioides difficile infection?

Vancomycin Dosing for Persistent Clostridioides difficile Infection

For persistent Clostridioides difficile infection (CDI), increase vancomycin to 500 mg orally four times daily, especially if the patient has severe or fulminant disease. 1, 2

Assessment of CDI Severity

Before adjusting the dose, assess the severity of the infection:

• Non-severe CDI: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL
• Severe CDI: WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL
• Fulminant CDI: Hypotension, shock, ileus, or megacolon

Dosing Recommendations Based on Severity

For Persistent Non-Severe or Severe CDI:

• If currently on 125 mg four times daily, consider:
  • Increasing to 500 mg four times daily 3
  • OR switching to fidaxomicin 200 mg twice daily for 10 days 1, 2

For Fulminant CDI:

• Vancomycin 500 mg orally four times daily
• If ileus is present, add vancomycin 500 mg per rectum every 6 hours as retention enema
• Add IV metronidazole 500 mg every 8 hours, particularly with ileus 1, 2

Evidence for Higher Dose Vancomycin

While the standard dose of vancomycin (125 mg four times daily) achieves fecal concentrations 500-1000 times higher than the C. difficile MIC 2, studies have shown:

1. Patients with ≥4 stools daily may have lower fecal vancomycin levels 4
2. Higher doses (500 mg four times daily) lead to consistently higher fecal levels (>2000 mg/L) 4
3. Some patients receiving 125 mg four times daily may have suboptimal levels (<50 mg/L) during the first day of treatment 4
4. "High dose" vancomycin (500 mg four times daily) has shown enhanced efficacy in patients not responding to conventional doses 3

Alternative Approaches for Persistent CDI

If the patient has had multiple recurrences:

1. Tapered and pulsed vancomycin regimen:

   • 125 mg four times daily for 10-14 days
   • Then 125 mg twice daily for 7 days
   • Then 125 mg once daily for 7 days
   • Then 125 mg every 2-3 days for 2-8 weeks 1, 2

2. Vancomycin followed by rifaximin:

   • Vancomycin 125 mg four times daily for 10 days
   • Followed by rifaximin 400 mg three times daily for 20 days 1

3. Fidaxomicin:

   • 200 mg twice daily for 10 days 1, 5

4. Fecal microbiota transplantation (FMT):

   • Consider after appropriate antibiotic treatments have failed for multiple recurrences 1, 2

Important Considerations

• Oral vancomycin is not systemically absorbed, making it safe to use higher doses 6
• Monitor renal function in patients >65 years as nephrotoxicity has been reported with oral vancomycin 6
• Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 2
• Avoid antiperistaltic agents and opiates as they may worsen the disease 2

Treatment Duration

• Continue treatment for at least 10 days
• Consider extending treatment to 14 days if response is delayed 1
• Evaluate treatment response after at least 3 days of therapy 2

By increasing the vancomycin dose to 500 mg four times daily for persistent CDI, you can achieve higher fecal concentrations that may overcome the infection, particularly in patients with severe or fulminant disease.