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

Treatment of Clostridioides difficile Infection (CDI)

For initial episodes of 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 fidaxomicin being preferred due to lower recurrence rates. 1, 2

Treatment Based on Disease Severity

Non-severe CDI

• Defined as: diarrhea without systemic signs of infection, WBC < 15,000 cells/mL, and serum creatinine < 1.5 times baseline 3
• First-line treatment options:
  • Vancomycin 125 mg orally four times daily for 10 days 3, 1
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Alternative (in resource-limited settings only):
  • Metronidazole 500 mg orally three times daily for 10-14 days 3, 1

Severe CDI

• Defined as: systemic signs of infection, WBC ≥ 15,000 cells/mL, or serum creatinine ≥ 1.5 times baseline 3, 2
• First-line treatment:
  • Vancomycin 125 mg orally four times daily for 10 days 3, 1
  • Fidaxomicin 200 mg orally twice daily for 10 days 3, 2

Fulminant/Complicated CDI

• Defined by: hypotension, shock, ileus, or megacolon 3
• Recommended treatment:
  • Vancomycin 500 mg orally four times daily plus intravenous metronidazole 500 mg three times daily 1
  • For patients unable to take oral medications: intravenous metronidazole 500 mg three times daily plus vancomycin retention enema 500 mg in 100 mL normal saline four times daily 3, 1

Treatment for Recurrent CDI

First Recurrence

• Preferred treatment:
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 4
  • Vancomycin 125 mg orally four times daily for 10 days 3, 2

Second or Subsequent Recurrences

• Recommended options:
  • Vancomycin in a tapered and pulsed regimen (e.g., 125 mg four times daily for 10-14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2-3 days for 2-8 weeks) 3, 2
  • Fidaxomicin extended regimen (200 mg twice daily for 5 days then once daily on alternate days on days 7-25) 3
  • Fecal microbiota transplantation (FMT) - strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 3, 1, 4

Important Clinical Considerations

• Discontinue the inciting antibiotic(s) as soon as possible to improve treatment outcomes and reduce recurrence risk 1, 2
• Clinical response typically requires 3-5 days after starting therapy 3
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2
• Do not perform "test of cure" after treatment completion 2
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those with continued antibiotic use 1

Special Populations

Pediatric Patients (6 Months to Less than 18 Years)

• For children weighing at least 12.5 kg and able to swallow tablets: one 200 mg fidaxomicin tablet twice daily for 10 days 5
• For children unable to swallow tablets: fidaxomicin oral suspension dosed by weight twice daily for 10 days 5

Common Pitfalls to Avoid

• Using metronidazole for severe or recurrent CDI (lower cure rates compared to vancomycin) 2, 4
• Administering only intravenous vancomycin for CDI (not effective) 2
• Failing to discontinue the inciting antibiotic (increases recurrence risk) 1, 2
• Using antiperistaltic agents and opiates (should be avoided) 3