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

Treatment of Clostridioides difficile Infection (C. diff)

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 first-line treatments, with metronidazole now reserved only for limited scenarios when access to vancomycin or fidaxomicin is limited. 1

Initial Treatment Based on Disease Severity

Non-severe CDI

• First-line options:
  • Oral vancomycin: 125 mg four times daily for 10 days 1
  • Fidaxomicin: 200 mg twice daily for 10 days 1, 2
• Alternative (only when access to vancomycin/fidaxomicin is limited):
  • Metronidazole: 500 mg orally three times daily for 10 days 1

Severe CDI

• First-line treatment:
  • Oral vancomycin: 125 mg four times daily for 10 days 3, 1
  • Fidaxomicin: 200 mg twice daily for 10 days 1, 2

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

• Oral vancomycin: 500 mg four times daily 3, 1
• PLUS intravenous metronidazole: 500 mg three times daily 3, 1
• If ileus present: Add intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 3

Treatment of Recurrent CDI

First Recurrence

• Treat as a first episode unless disease has progressed from non-severe to severe 3
• Fidaxomicin is preferred due to lower recurrence rates compared to vancomycin (19.7% vs 35.5%) 1

Second or Subsequent Recurrences

• Vancomycin with taper/pulse strategy: 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 3
• OR fidaxomicin: 200 mg twice daily for 10 days 1, 2
• Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy 1, 4
• Fecal microbiota transplantation (FMT) after appropriate antibiotic treatment failures, with success rates up to 90% 1, 5, 4

Special Populations

Patients Unable to Take Oral Medications

• Intravenous metronidazole: 500 mg three times daily for 10 days 3
• PLUS intracolonic vancomycin: 500 mg in 100 mL normal saline every 4-12 hours 3
• AND/OR vancomycin: 500 mg four times daily via nasogastric tube 3

Pediatric Patients (6 months and older)

• For children weighing ≥12.5 kg who can swallow tablets: fidaxomicin 200 mg tablet twice daily for 10 days 1, 2
• For younger children: weight-based dosing of oral vancomycin or fidaxomicin suspension 3, 2

Surgical Management

Colectomy should be considered in cases of:

• Perforation of the colon
• Systemic inflammation not responding to antibiotic therapy
• Toxic megacolon or severe ileus 3

Additional Important Measures

Infection Control

• Isolate patients until 48 hours after diarrhea resolution 1
• Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores) 1
• Environmental cleaning with sporicidal agents 1

Prevention of Recurrence

• Discontinue the inciting antibiotic if possible 1
• Review and discontinue proton pump inhibitors if not medically necessary 1
• Consider prophylactic low-dose vancomycin (125 mg daily) during future antibiotic courses for patients with history of CDI 1

Treatment Pitfalls to Avoid

1. Do not repeat testing for cure if symptoms resolve 1
2. Do not use metronidazole for severe CDI or multiple recurrences 1, 4
3. Do not delay surgical consultation in fulminant cases 3
4. Do not use alcohol-based hand sanitizers for hand hygiene when caring for C. difficile patients 1
5. Do not continue unnecessary antibiotics during CDI treatment 3, 1

The treatment landscape for C. difficile has evolved significantly, with vancomycin and fidaxomicin now firmly established as first-line agents, replacing metronidazole which was previously widely used. For recurrent cases, FMT has emerged as a highly effective option with cure rates of 70-90%, particularly beneficial for elderly patients who may not be surgical candidates 5, 6.