What is the treatment for Clostridioides difficile (C. diff) infection?

Treatment of Clostridioides difficile Infection

The first-line treatment for Clostridioides difficile infection (CDI) is fidaxomicin 200 mg twice daily for 10 days, which has demonstrated lower recurrence rates compared to other treatments. 1

Initial Treatment Based on Disease Severity

Non-Severe CDI

• First-line options:
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Oral vancomycin 125 mg four times daily for 10 days 3, 1
• Alternative option (less preferred):
  • Stop inducing antibiotic(s) and observe clinical response for 48 hours (only for very mild cases with <4 stools/day and no signs of severe colitis) 3, 1

Severe CDI

• First-line options:
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Oral vancomycin 125 mg four times daily for 10 days 3, 1
• Note: Higher doses of vancomycin (500 mg four times daily) have shown equal cure rates to standard dosing 3

Fulminant CDI/Unable to Take Oral Medications

• Intravenous metronidazole 500 mg three times daily for 10 days PLUS one of the following:
  • Vancomycin retention enema 500 mg in 100 mL normal saline four times daily for 10 days 3
  • Vancomycin 500 mg four times daily via nasogastric tube for 10 days 3
• Consider intravenous tigecycline 50 mg twice daily for 14 days as salvage therapy in refractory cases 3

Treatment of Recurrent CDI

1. First recurrence:

   • Fidaxomicin 200 mg twice daily for 10 days 1
   • Extended-pulsed fidaxomicin regimen: 200 mg twice daily for 5 days, followed by 200 mg once daily on alternate days for days 7-25 1

2. Second or subsequent recurrences:

   • Vancomycin in a tapered and pulsed regimen 1
   • Consider fecal microbiota transplantation (FMT) for multiple recurrences 4, 5
   • Consider adjunctive bezlotoxumab (especially for high-risk patients) 5, 6

Special Considerations

Surgical Evaluation

Prompt surgical consultation for patients with:

• Perforation of the colon
• Systemic inflammation not responding to antibiotics
• Toxic megacolon
• Severe ileus
• Serum lactate >5.0 mM 3

Adjunctive Measures

• Discontinue the inciting antibiotic as soon as possible 1
• Review and discontinue unnecessary proton pump inhibitors 1
• For patients requiring antibiotics while recovering from CDI: consider low-dose oral vancomycin (125 mg once daily) as prophylaxis 1

Monitoring Response

• Evaluate treatment response after at least 3 days of therapy
• Monitor for decreased stool frequency and improved stool consistency
• Follow patients for at least 8 weeks after treatment to assess for recurrence 1

Infection Control

• Implement isolation until 48 hours after diarrhea resolution
• Use appropriate hand hygiene and environmental cleaning measures 1

Common Pitfalls to Avoid

1. Using metronidazole as first-line therapy (now considered inferior) 5, 7
2. Failing to discontinue the inciting antibiotic
3. Not considering surgical evaluation in severe or fulminant cases
4. Repeating C. difficile testing during or shortly after treatment (may remain positive despite clinical cure)
5. Treating asymptomatic carriers

The treatment landscape for C. difficile has evolved significantly, with fidaxomicin and vancomycin now being the cornerstones of therapy 5. While metronidazole was historically used as first-line treatment, current guidelines no longer recommend it as primary therapy due to inferior outcomes 1, 5.