What is the recommended treatment for a patient with Clostridium (C.) difficile infection where both toxins are positive?

Treatment for Clostridium difficile Infection with Positive Toxins

For a patient with Clostridium difficile infection with both toxins positive, oral vancomycin 125 mg four times daily for 10 days is the recommended first-line treatment. 1, 2

Disease Severity Assessment

Disease severity should guide treatment choice:

• Non-severe CDI: Characterized by stool frequency <4 times daily, no signs of severe colitis, and white blood cell count <15 × 10^9/L 1, 2
• Severe CDI: Characterized by one or more of the following 1, 2:
  • Marked leukocytosis (>15 × 10^9/L)
  • Serum albumin <3.0 g/dL
  • Rise in serum creatinine (>50% above baseline)
  • Temperature >38.5°C
  • Pseudomembranous colitis on endoscopy
  • Signs of severe colitis on imaging

First-Line Treatment Algorithm

Non-severe CDI:

• Metronidazole 500 mg orally three times daily for 10 days 1
• OR Vancomycin 125 mg orally four times daily for 10 days 1, 3

Severe CDI:

• Vancomycin 125 mg orally four times daily for 10 days 1, 3
• Higher doses (up to 500 mg four times daily) have been used in some severe cases but have not shown significant clinical benefit in outcomes 4

Fulminant CDI (with hypotension, shock, ileus, or megacolon):

• Vancomycin 500 mg orally four times daily plus
• Metronidazole 500 mg IV every 8 hours 1
• If ileus present: Add vancomycin enema 500 mg in 100 mL normal saline every 6 hours 1

Alternative Treatment Options

• Fidaxomicin: 200 mg orally twice daily for 10 days 5
  • Similar clinical cure rates to vancomycin but lower recurrence rates (15.4% vs 25.3%) 6
  • Consider for patients at high risk for recurrence (elderly, immunocompromised, or receiving concomitant antibiotics) 1
  • Higher cost may limit use as first-line therapy 1

Treatment of Recurrent CDI

First recurrence:

• Use the same treatment as for initial episode based on severity 1
• Consider fidaxomicin instead of vancomycin for lower recurrence risk 7

Second or subsequent recurrence:

• Vancomycin 125 mg four times daily for 10-14 days, followed by tapered and/or pulsed regimen 1
• Vancomycin taper example: 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
• Fidaxomicin 200 mg twice daily for 10 days 1, 5
• Consider fecal microbiota transplantation for multiple recurrences 1

Special Considerations

• Avoid antiperistaltic agents and opiates as they may mask symptoms and potentially worsen disease 1, 2
• Discontinue the inciting antibiotic if possible 1
• For patients with multiple recurrences who cannot access fecal microbiota transplantation, prolonged oral vancomycin at 125 mg once daily may be effective as secondary prophylaxis 8
• Vancomycin levels in stool are typically much higher than the MIC90 against C. difficile, even with standard dosing 9

Monitoring Response

• Clinical response is typically observed as decreased stool frequency and improved stool consistency within 3-5 days of treatment initiation 1
• "Test of cure" is not recommended after CDI treatment 1
• Monitor for signs of treatment failure or complications requiring surgical intervention 1