What is the recommended medication for outpatient treatment of Clostridioides difficile (C. diff) infection?

Treatment of Clostridioides difficile Infection in Outpatients

For outpatient treatment of Clostridioides difficile infection (CDI), fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment, with oral vancomycin 125 mg four times daily for 10 days as an acceptable alternative. 1, 2

First-Line Treatment Options

Preferred Treatment:

• Fidaxomicin 200 mg orally twice daily for 10 days
  • FDA-approved for adults and pediatric patients ≥6 months 3
  • Associated with lower recurrence rates compared to vancomycin 4, 5
  • Particularly beneficial for patients at higher risk for recurrence (elderly, those receiving concomitant antibiotics) 1, 2

Alternative Treatment:

• Vancomycin 125 mg orally four times daily for 10 days
  • Remains an effective alternative when fidaxomicin is unavailable or cost-prohibitive 1, 6
  • Higher-dose vancomycin (500 mg four times daily) has not shown significant benefits over the standard 125 mg dose for non-severe CDI 7, 8

Limited Alternative (for non-severe CDI only):

• Metronidazole 500 mg orally three times daily for 10-14 days
  • Only recommended for non-severe CDI when fidaxomicin and vancomycin are unavailable 1, 2
  • Non-severe CDI defined as: WBC ≤15,000 cells/μL and serum creatinine <1.5 mg/dL 1
  • Less effective than vancomycin for severe CDI 1

Treatment for Recurrent CDI

For patients experiencing their first CDI recurrence:

1. Fidaxomicin 200 mg twice daily for 10 days

   • OR fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1, 2

2. Vancomycin in a tapered and pulsed regimen

   • Example 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, 2

3. Consider adjunctive bezlotoxumab 10 mg/kg IV once during antibiotic treatment for patients at high risk of recurrence 1, 2

   • Use with caution in patients with congestive heart failure

Treatment for Severe or Fulminant CDI

For patients with severe or fulminant CDI (hypotension, shock, ileus, or megacolon):

• Vancomycin 500 mg orally four times daily 1
• If ileus is present, consider adding:
  • Rectal vancomycin 500 mg in 100 mL normal saline four times daily as retention enema
  • IV metronidazole 500 mg every 8 hours 1

Important Clinical Considerations

1. Monitoring response:

   • Expect decreased stool frequency and improved consistency within 3 days of starting treatment 2
   • If no improvement after 3-4 days, reassess diagnosis and treatment

2. Discontinue the inciting antibiotic as soon as clinically feasible to reduce recurrence risk 2

3. Avoid antiperistaltic agents and opiates as they may mask symptoms and potentially worsen disease 2

4. Common pitfalls to avoid:

   • Using metronidazole as first-line therapy for severe CDI 2
   • Failure to recognize fulminant CDI requiring urgent intervention 2
   • Inadequate duration of therapy (ensure full 10-day course is completed) 2

5. For multiple recurrences (≥2 recurrences):

   • Consider fecal microbiota transplantation after appropriate antibiotic treatments have been tried 1, 2

Special Populations

Pediatric Patients:

• Fidaxomicin is FDA-approved for patients ≥6 months of age 3
• For children ≥6 months: weight-based dosing of fidaxomicin oral suspension twice daily for 10 days 2, 3
• Alternative: vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 2

Elderly Patients:

• Monitor renal function during and after treatment with vancomycin, even in those with normal baseline renal function 6
• Consider fidaxomicin as first-line due to lower recurrence rates in this high-risk population 2, 4

By following these evidence-based recommendations, clinicians can optimize treatment outcomes for outpatients with C. difficile infection while minimizing the risk of recurrence and complications.