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

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of Clostridioides difficile infection, either oral vancomycin or fidaxomicin is recommended as first-line therapy over metronidazole, with treatment selection based on disease severity. 1

Initial CDI Episode Treatment

Non-severe CDI

• Defined as: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 1
• First-line treatment options:
  • Vancomycin 125 mg orally 4 times daily for 10 days 1
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Alternative (only if access to vancomycin or fidaxomicin is limited):
  • Metronidazole 500 mg orally 3 times daily for 10 days 1
  • Avoid repeated metronidazole courses due to risk of irreversible neurotoxicity 1

Severe CDI

• Defined as: WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 1
• First-line treatment options:
  • Vancomycin 125 mg orally 4 times daily for 10 days 1
  • Fidaxomicin 200 mg orally twice daily for 10 days 1
• Higher doses of vancomycin (500 mg four times daily) have not shown significant differences in clinical outcomes compared to standard doses 1, 3

Fulminant CDI

• Defined as: Hypotension, shock, ileus, or megacolon 1
• Treatment regimen:
  • Vancomycin 500 mg orally 4 times daily 1
  • PLUS intravenous metronidazole 500 mg every 8 hours 1
  • If ileus present: Add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as retention enema 1

Recurrent CDI Treatment

First Recurrence

• If metronidazole was used for initial episode:
  • Vancomycin 125 mg orally 4 times daily for 10 days 1
• If standard regimen was used for initial episode:
  • Prolonged tapered and pulsed vancomycin regimen (e.g., 125 mg 4 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
  • OR fidaxomicin 200 mg twice daily for 10 days if vancomycin was used initially 1

Second or Subsequent Recurrence

• Treatment options:
  • Vancomycin in a tapered and pulsed regimen 1
  • Vancomycin 125 mg 4 times daily for 10 days followed by rifaximin 400 mg 3 times daily for 20 days 1
  • Fidaxomicin 200 mg twice daily for 10 days 1
  • Fecal microbiota transplantation (particularly effective for multiple recurrences) 1, 4

Special Situations

NPO (Nil Per Os) Patients

• For patients unable to take oral medications:
  • Intravenous metronidazole 500 mg every 8 hours PLUS vancomycin retention enema 500 mg in 100 mL normal saline 4 times daily 1, 5
  • Once oral intake is possible, transition to oral vancomycin or fidaxomicin to complete the course 5

Important Clinical Considerations

• Discontinue the inciting antibiotic(s) as soon as possible to reduce recurrence risk 1
• Start empiric therapy when substantial laboratory confirmation delay is expected 1
• Standard duration of therapy is 10 days, but may need extension to 14 days if response is delayed 5
• Oral vancomycin is not systemically absorbed, making it safe for prolonged use 6
• Fidaxomicin has been associated with lower recurrence rates compared to vancomycin, particularly after first recurrence 1, 2
• Faecal vancomycin levels are proportional to dosage and remain well above the MIC90 for C. difficile even in patients with frequent stools 7
• Vancomycin capsules and compounded oral solution show similar efficacy for treating severe CDI 8

Common Pitfalls to Avoid

• Using metronidazole for severe or recurrent CDI (lower cure rates compared to vancomycin) 1
• Failing to discontinue the inciting antibiotic, which increases recurrence risk 1
• Administering only intravenous vancomycin for CDI (not effective as it is not excreted into the colon) 5, 6
• Performing "test of cure" after treatment completion (not recommended) 5
• Underestimating recurrence risk (approximately 20% of patients experience recurrence) 9
• Using repeated or prolonged courses of metronidazole due to neurotoxicity risk 1