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

Treatment of Clostridioides difficile Infection

For initial 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 fidaxomicin preferred due to significantly lower recurrence rates. 1, 2

Initial Episode Treatment

Non-Severe CDI

Non-severe disease is defined as WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 2:

• First-line options:

  • Vancomycin 125 mg orally four times daily for 10 days 1, 2
  • Fidaxomicin 200 mg orally twice daily for 10 days (preferred due to lower recurrence rates) 1, 2

• Resource-limited settings: Metronidazole 500 mg orally three times daily for 10 days can be considered, but has lower efficacy than vancomycin, particularly in severe cases 1

Severe CDI

Severe disease is defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 2:

• First-line options:

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

• Important note: Vancomycin demonstrated superior cure rates compared to metronidazole in severe CDI (97% vs. 76%) 1

• Higher doses (500 mg four times daily) have not shown significant differences in clinical outcomes compared to standard 125 mg doses 2, 3

Fulminant/Complicated CDI

For patients with hypotension, shock, ileus, or megacolon 4:

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 1, 2

• If unable to take oral medications:

  • IV metronidazole 500 mg three times daily PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1, 2
  • Consider vancomycin 500 mg four times daily via nasogastric tube 4

• Surgical consultation: Colectomy should be performed for colonic perforation or systemic inflammation not responding to antibiotics; operate before serum lactate exceeds 5.0 mmol/L 4

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option 1, 2
• Alternative: Vancomycin as a tapered and pulsed regimen rather than a standard 10-day course 1, 2
• Fidaxomicin reduced recurrence rates to 19.7% compared to 35.5% with vancomycin in patients with first recurrence 5

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen:

  • 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 4, 6

• Alternative options:

  • Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 2
  • Fidaxomicin 200 mg twice daily for 10 days 2

• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 1, 2

Critical Management Principles

Essential Actions

• Discontinue the inciting antibiotic agent(s) as soon as possible 1, 2
• Mild CDI (stool frequency <4 times daily) clearly induced by antibiotics may be treated by stopping the inducing antibiotic alone, with close observation 4

Medications to Avoid

• Antiperistaltic agents and opiates should be avoided 4
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2, 6

Treatment Response Monitoring

• Clinical response typically requires 3-5 days after starting therapy 4, 1
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those with continued antibiotic use 1
• Do not perform a "test of cure" after treatment completion 2

Common Pitfalls to Avoid

• Using metronidazole for severe or recurrent CDI is not recommended due to lower cure rates compared to vancomycin 2
• Administering only intravenous vancomycin for CDI is not effective - oral or rectal administration is required 2
• Failing to discontinue the inciting antibiotic increases recurrence risk 2
• Using repeated or prolonged courses of metronidazole should be avoided due to neurotoxicity risk 1, 2