What is the recommended management for Clostridioides difficile (C diff) infection?

Management of Clostridioides difficile Infection

For the treatment of C. difficile infection (CDI), either oral vancomycin or fidaxomicin is strongly recommended over metronidazole as first-line therapy, with treatment regimens tailored to disease severity and recurrence status. 1

Classification and Initial Assessment

Disease severity guides treatment approach:

• Non-severe CDI: WBC ≤15,000 cells/μL and serum creatinine <1.5 mg/dL
• Severe CDI: WBC ≥15,000 cells/μL or serum creatinine >1.5 mg/dL
• Fulminant CDI: Hypotension, shock, ileus, or megacolon

Treatment Algorithm by Clinical Scenario

Initial Episode

Non-severe or Severe CDI:

• First-line:

  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • OR Vancomycin 125 mg orally four times daily for 10 days 1

• Alternative (only if access to first-line agents is limited):

  • Metronidazole 500 mg orally three times daily for 10-14 days 1
  • Note: Avoid repeated/prolonged courses due to risk of cumulative neurotoxicity 1

Fulminant CDI:

• Vancomycin 500 mg orally four times daily 1, 3
• If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1
• Add IV metronidazole 500 mg every 8 hours 1, 3
• Obtain surgical consultation for all patients with fulminant CDI 3
• Consider surgery before serum lactate exceeds 5.0 mmol/L 3

First Recurrence

• Preferred: Fidaxomicin 200 mg twice daily for 10 days 1, 3

  • Alternative regimen: Fidaxomicin 200 mg twice daily for 5 days, then once every other day for 20 days 3

• Alternatives:

  • Vancomycin in tapered and pulsed 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, 3
  • Vancomycin 125 mg four times daily for 10 days (if metronidazole was used for initial episode) 1

• Adjunctive treatment to consider:

  • Bezlotoxumab 10 mg/kg IV once during antibiotic treatment (especially for patients >65 years, immunocompromised, or with severe CDI) 1, 3
  • Note: Use with caution in patients with congestive heart failure 1

Second or Subsequent Recurrence

• Fidaxomicin 200 mg twice daily for 10 days 1
• Vancomycin in tapered and pulsed regimen (as described above) 1
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Fecal microbiota transplantation (FMT) after at least 2 recurrences with appropriate antibiotic treatment failures 1, 3, 4
  • Success rates of 80-90% in preventing further recurrences 3
  • Particularly beneficial for elderly patients who may not be surgical candidates 4

Additional Management Principles

1. Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1, 3

2. Infection control measures:

   • Isolate patients with suspected or confirmed CDI 3
   • Hand hygiene with soap and water (preferred over alcohol-based sanitizers) 1, 3
   • Environmental cleaning with sporicidal agents 1, 3

3. Antibiotic stewardship:

   • Minimize frequency and duration of high-risk antibiotics 1, 3
   • Target restriction of fluoroquinolones, clindamycin, and cephalosporins 1

4. Monitoring:

   • Follow patients for at least 8 weeks after treatment to assess for recurrence 3
   • Do not perform repeat testing for cure if symptoms resolve 3

Special Considerations

• Loading doses: Consider higher initial doses (250 mg or 500 mg QID) of vancomycin during the first 24-48 hours of treatment, particularly in severe cases with frequent diarrhea, followed by standard dosing 5

  • Faecal vancomycin levels are proportional to the dosage administered and remain well above the MIC90 for C. difficile even with frequent stools 5
  • However, limited data suggests no significant difference in clinical outcomes between high-dose and low-dose vancomycin regimens for severe CDI 6, 7

• Pediatric patients: Treatment options similar to adults with weight-based dosing 1, 2

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

• Immunocompromised patients: Higher risk for recurrence; consider adjunctive bezlotoxumab 3

By following this evidence-based approach to CDI management, clinicians can optimize treatment outcomes while minimizing recurrence risk and complications.