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

Treatment for Clostridioides difficile Infection

For C. difficile infection, oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) are the recommended first-line treatments, with treatment choice based on disease severity and risk of recurrence. 1

Treatment Based on Disease Severity

Non-Severe CDI

• First-line options:
  • Oral vancomycin: 125 mg four times daily for 10 days 1
  • Oral fidaxomicin: 200 mg twice daily for 10 days 1, 2
  • Metronidazole can be considered in younger patients with mild-to-moderate disease and few risk factors for recurrence: 500 mg three times daily for 10 days 3

Severe CDI

• First-line:
  • Oral vancomycin: 125 mg four times daily for 10 days 1
  • Oral fidaxomicin: 200 mg twice daily for 10 days 1, 2

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

• Oral vancomycin: 500 mg four times daily 1
• PLUS intravenous metronidazole: 500 mg three times daily 4, 1
• If ileus present: Add intracolonic vancomycin: 500 mg in 100 mL normal saline every 4-12 hours 4, 1

Treatment When Oral Therapy Is Not Possible

• Intravenous metronidazole: 500 mg three times daily for 10 days 4
• PLUS one of the following:
  • Intracolonic vancomycin: 500 mg in 100 mL normal saline every 4-12 hours 4
  • Vancomycin via nasogastric tube: 500 mg four times daily 4

Treatment of Recurrent CDI

First Recurrence

• Treat as a first episode unless disease has progressed from non-severe to severe 4
• Consider fidaxomicin over vancomycin due to lower recurrence rates 1, 3

Second or Subsequent Recurrences

• Vancomycin taper/pulse 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 4, 1
• OR extended-pulsed fidaxomicin regimen: 200 mg twice daily for days 1-5, then 200 mg once every other day for days 6-25 1
• Fecal microbiota transplantation (FMT) should be offered after multiple recurrences 1, 3, 5
• Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy for patients with high risk of recurrence 3

Pediatric Dosing

• Metronidazole: 7.5 mg/kg/dose (max 500 mg) three or four times daily 4
• Vancomycin: 10 mg/kg/dose (max 125 mg) four times daily 4
• Fidaxomicin: Approved for children aged 6 months and older 2

Surgical Management

Surgical consultation should be obtained for all patients with fulminant CDI. Colectomy should be performed in cases of:

• Perforation of the colon 4
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy 4
• Toxic megacolon or severe ileus 4
• Surgery should be performed before serum lactate exceeds 5.0 mmol/L 4, 1

Important Considerations

1. Discontinue the inciting antibiotic as soon as possible 4, 1
2. Avoid antiperistaltic agents and opiates especially in acute settings 1
3. Implement infection control measures:
   • Isolate patients with suspected CDI 4, 1
   • Hand hygiene with soap and water (preferred during outbreaks) 1
   • Environmental cleaning with sporicidal agents 1

Treatment Pitfalls to Avoid

1. Do not use metronidazole as first-line therapy for adults with CDI except in mild cases with limited risk factors 3, 5
2. Do not repeat C. difficile testing during the same episode or as a "test of cure" 1
3. Do not use prophylactic antibiotics for CDI prevention 4
4. Do not delay surgical consultation in fulminant cases, as mortality increases with delayed intervention 4, 1
5. Do not use probiotics for prevention of CDI as recommended by the Infectious Diseases Society of America 5

Risk Factors for Severe or Recurrent CDI

• Age > 65 years 1
• Continued use of antibiotics unrelated to CDI treatment 1
• Comorbidities (especially immunocompromised status) 3
• Previous CDI episodes 1
• Healthcare facility exposure 3, 6

The treatment landscape for C. difficile has evolved significantly, with vancomycin and fidaxomicin now preferred over metronidazole due to higher cure rates and lower recurrence rates 3, 5. For multiple recurrences, fecal microbiota transplantation has shown excellent success rates of 80-90% 1.