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

Vancomycin Dosing for C. difficile Infection

For an initial episode of C. difficile infection, vancomycin 125 mg orally four times daily for 10 days is the recommended dose, regardless of disease severity. 1, 2

Initial Episode Dosing

Non-Severe CDI

• Vancomycin 125 mg orally four times daily for 10 days is the standard dose 1, 2
• This dose is preferred over metronidazole based on current IDSA/SHEA 2018 guidelines 1
• Non-severe disease is defined as WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 1

Severe CDI

• Vancomycin 125 mg orally four times daily for 10 days remains the recommended dose 1, 2
• Despite intuition to increase dosing for severe disease, higher doses (500 mg four times daily) have not demonstrated superior outcomes 3, 4, 5
• Severe disease is defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 1

Fulminant CDI

• Vancomycin 500 mg orally four times daily is recommended for fulminant cases 1, 2
• If ileus is present, add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as a retention enema 1
• Intravenous metronidazole 500 mg every 8 hours should be administered concurrently, particularly if ileus is present 1
• Fulminant disease includes hypotension, shock, ileus, or megacolon 1

Recurrent CDI Dosing

First Recurrence

• Vancomycin 125 mg four times daily for 10 days if metronidazole was used initially 1
• Alternatively, use a prolonged tapered and pulsed vancomycin 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 1

Second or Subsequent Recurrences

• Vancomycin tapered and pulsed regimen is the preferred approach 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, 6

Pediatric Dosing

• 40 mg/kg/day divided into 3 or 4 doses for 7-10 days (maximum 2 g/day) 2
• For non-severe CDI: 10 mg/kg/dose (maximum 125 mg) four times daily for 10 days 1
• For severe/fulminant CDI: 10 mg/kg/dose (maximum 500 mg) every 8 hours for 10 days 1

Critical Dosing Considerations

Evidence Against High-Dose Vancomycin

• Multiple studies demonstrate that vancomycin 125 mg four times daily is equally effective as 500 mg four times daily for non-fulminant CDI 3, 4, 5
• A randomized trial of 46 patients showed no difference in treatment failure, duration of diarrhea, or time to cure between 125 mg and 500 mg doses 4
• A meta-analysis found no significant reduction in recurrence rates with high-dose versus low-dose vancomycin (OR 2.058,95% CI: 0.653-6.489) 5
• The 125 mg dose is preferred due to lower cost without compromising efficacy 4

Route of Administration

• Oral administration is essential - parenteral vancomycin is not effective for CDI 2
• Vancomycin is poorly absorbed orally, achieving fecal concentrations >100 mg/kg with minimal systemic absorption 2
• For patients unable to take oral medications, vancomycin can be administered via nasogastric tube 1

Special Monitoring Situations

• Patients >65 years of age require renal function monitoring during and after treatment due to increased nephrotoxicity risk 2
• Serum vancomycin levels may be detectable in patients with inflammatory bowel disease or renal impairment, warranting monitoring in select cases 2
• Avoid repeated or prolonged courses of metronidazole due to cumulative neurotoxicity risk 1

Adjunctive Management

• Discontinue the inciting antibiotic immediately if possible 1, 7
• Avoid antiperistaltic agents and opiates entirely as they worsen outcomes 1, 8
• Consider surgical consultation (colectomy) for perforation, toxic megacolon, severe ileus, or serum lactate >5.0 mmol/L 1, 8