What is the recommended treatment for a patient diagnosed with Clostridioides difficile (C. difficile)?

Treatment of Clostridioides difficile Infection (CDI)

For initial episodes of C. difficile infection, either vancomycin (125 mg orally four times daily for 10 days) or fidaxomicin (200 mg orally twice daily for 10 days) is recommended over metronidazole as first-line therapy. 1

Treatment Algorithm Based on Disease Severity

Initial CDI Episode

Non-severe CDI

(WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL)

• Preferred treatment: Fidaxomicin 200 mg orally twice daily for 10 days 1
• Alternative treatment: Vancomycin 125 mg orally four times daily for 10 days 1
• Alternative if above agents unavailable: Metronidazole 500 mg orally three times daily for 10-14 days (only for non-severe cases) 1
• Discontinue the inciting antibiotic agent(s) as soon as possible 1

Severe CDI

(WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL)

• Preferred treatment: Vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days 1
• Avoid metronidazole for severe cases due to lower cure rates (76% vs 97% with vancomycin) 2

Fulminant CDI

(Hypotension, shock, ileus, or megacolon)

• Vancomycin 500 mg orally four times daily 1
• If ileus present, add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as retention enema 1
• Intravenous metronidazole 500 mg every 8 hours should be administered together with oral or rectal vancomycin 1

Recurrent CDI

First Recurrence

• If metronidazole was used for initial episode: Vancomycin 125 mg orally four times daily for 10 days 1
• If standard vancomycin was used for initial episode:
  • Vancomycin in a tapered and pulsed regimen (125 mg four times daily for 10-14 days, then twice daily for 7 days, once daily for 7 days, then every 2-3 days for 2-8 weeks) 1 OR
  • Fidaxomicin 200 mg twice daily for 10 days 1, 3
• Fidaxomicin has shown lower recurrence rates compared to vancomycin (19.7% vs 35.5%) 3

Second or Subsequent Recurrence

• Vancomycin in a tapered and pulsed regimen 1
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Fidaxomicin 200 mg twice daily for 10 days 1
• Fecal microbiota transplantation (FMT) after appropriate antibiotic treatments for at least 2 recurrences (3 CDI episodes) have failed 1
• For patients without access to FMT or who have failed FMT, prolonged vancomycin at 125 mg once daily has shown effectiveness as secondary prophylaxis 4

Special Populations

Pediatric Patients

• Non-severe initial episode or first recurrence: Either metronidazole (7.5 mg/kg/dose three or four times daily) or vancomycin (10 mg/kg/dose four times daily) for 10 days 1
• Severe/fulminant: Vancomycin (10 mg/kg/dose four times daily) with or without IV metronidazole 1
• Second or subsequent recurrence: Similar approach to adults with dose adjustments 1

Important Clinical Considerations

• Dosing considerations: Higher doses of vancomycin (500 mg four times daily vs 125 mg four times daily) have not shown significant differences in cure rates for severe CDI but may potentially reduce recurrence rates 5, 6
• Duration of therapy: Standard duration is 10 days, but consider extending to 14 days if response is delayed, particularly with metronidazole 1
• Monitoring: For patients >65 years, monitor renal function during and after treatment with vancomycin due to risk of nephrotoxicity, even with oral administration 7
• Empiric therapy: Consider starting empiric treatment when substantial delay in laboratory confirmation is expected or for fulminant CDI 1
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1

Common Pitfalls to Avoid

• Overuse of metronidazole: Using metronidazole for severe CDI leads to lower cure rates 2
• Inadequate follow-up: "Test of cure" is not recommended after CDI treatment 1
• Failure to discontinue inciting antibiotics: This may influence the risk of CDI recurrence 1
• Inappropriate route of administration: Vancomycin must be given orally for CDI; parenteral administration is not effective for intestinal infections 7
• Underestimating recurrence risk: Approximately 20% of patients experience recurrence; higher risk in elderly patients and those with continued antibiotic use 1, 4