What is the treatment for Clostridioides difficile (Cdiff) infection?

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of Clostridioides difficile infection, oral vancomycin 125 mg four times daily for 10 days is recommended as first-line therapy for both non-severe and severe CDI. 1

Disease Severity Classification

• CDI severity should be assessed before selecting treatment to guide appropriate therapy 1, 2:
  • Non-severe CDI: stool frequency <4 times daily, leukocytosis with WBC ≤15,000 cells/mL, serum creatinine <1.5 mg/dL, and no signs of severe colitis 1
  • Severe CDI: leukocytosis with WBC ≥15,000 cells/mL, serum creatinine >1.5 mg/dL, temperature >38.5°C, hemodynamic instability, or evidence of pseudomembranous colitis 1, 3

First-Line Treatment Recommendations

Non-severe CDI:

• First choice: Oral vancomycin 125 mg four times daily for 10 days 1, 3
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days (particularly for patients at high risk of recurrence) 1, 4
• Less preferred: Oral metronidazole 500 mg three times daily for 10 days (only when access to vancomycin or fidaxomicin is limited) 3, 2

Severe CDI:

• First choice: Oral vancomycin 125 mg four times daily for 10 days 3, 1
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 1, 4

Fulminant CDI (severe and complicated):

• Oral vancomycin 500 mg four times daily plus intravenous metronidazole 500 mg three times daily 3, 1
• If ileus is present: Add rectal vancomycin 500 mg in 100 mL normal saline every 4-12 hours as retention enema 3, 1

Important Clinical Considerations

• Discontinue the inciting antibiotic(s) as soon as possible to reduce the risk of CDI recurrence 3, 1
• Avoid antimotility agents and opiates, especially in the acute setting, as they may worsen outcomes 3, 1
• Start empiric therapy if substantial delay in laboratory confirmation is expected (>48 hours) or for fulminant CDI 1, 2
• Consider discontinuing unnecessary proton pump inhibitors in patients at high risk for CDI 1

Treatment of Recurrent CDI

• First recurrence: Treat based on severity using the same criteria as initial episode 3, 1

  • Consider fidaxomicin 200 mg twice daily for 10 days if not used for initial episode 1, 5

• Second or subsequent recurrences 3, 1:

  • Oral vancomycin 125 mg four times daily for at least 10 days, followed by a tapered and pulsed regimen (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 3
  • Consider fecal microbiota transplantation for multiple recurrences that have failed appropriate antibiotic treatments 1, 6

Surgical Management

• Consider colectomy in cases of 3, 1:
  • Perforation of the colon
  • Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
  • Toxic megacolon or severe ileus
• Surgery should be performed before serum lactate exceeds 5.0 mmol/L 3

Common Pitfalls and Caveats

• Metronidazole is associated with increasing treatment failures and should be limited to initial episodes of mild-moderate CDI when other options are unavailable 2, 6
• Repeated or prolonged courses of metronidazole should be avoided due to risk of cumulative and potentially irreversible neurotoxicity 2
• Fidaxomicin has been shown to reduce the risk of recurrence compared to vancomycin but is more expensive 5, 7
• Hand hygiene with soap and water is required, as alcohol-based hand sanitizers are ineffective against C. difficile spores 1
• Treatment duration may need to be extended beyond 10 days in patients with delayed response to therapy 1