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

Treatment of Clostridioides difficile Infection

For initial episodes of C. difficile infection (CDI), either oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) is strongly recommended as first-line therapy, with treatment selection based on disease severity. 1, 2

Treatment Algorithm Based on Disease Severity

Initial Episode Treatment

Non-severe CDI

• Definition: WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL
• Recommended treatment:
  • Vancomycin 125 mg orally four times daily for 10 days, OR
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Metronidazole 500 mg orally three times daily for 10 days only if access to vancomycin or fidaxomicin is limited 1

Severe CDI

• Definition: WBC ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL OR serum albumin <30 g/L 1, 2
• Recommended treatment:
  • Vancomycin 125 mg orally four times daily for 10 days, OR
  • Fidaxomicin 200 mg orally twice daily for 10 days 1

Fulminant CDI

• Definition: Hypotension, shock, ileus, or toxic megacolon 1
• Recommended treatment:
  • Vancomycin 500 mg orally four times daily, AND
  • Metronidazole 500 mg intravenously every 8 hours 1
  • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline as retention enema every 6 hours 1

Critical Management Steps

1. Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1
2. Start empiric therapy when substantial delay in laboratory confirmation is expected 1
3. Consider extending treatment duration to 14 days in patients with delayed response, particularly with metronidazole 1
4. Avoid antiperistaltic agents and opioids as they can worsen symptoms 2

Recurrent CDI Treatment

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 tapered and pulsed regimen (125 mg four 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), OR
  • Fidaxomicin 200 mg twice daily for 10 days 1, 2

Second or Subsequent Recurrence

• Vancomycin in tapered and pulsed regimen, OR
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days, OR
• Fidaxomicin 200 mg twice daily for 10 days, OR
• Fecal microbiota transplantation (FMT) 1, 2

Pediatric Treatment (6 months to <18 years)

Non-severe CDI

• Metronidazole 7.5 mg/kg/dose three or four times daily for 10 days (maximum 500 mg per dose), OR
• Vancomycin 10 mg/kg/dose four times daily for 10 days (maximum 125 mg per dose) 1

Severe/Fulminant CDI

• Vancomycin 10 mg/kg/dose four times daily for 10 days (maximum 500 mg per dose) with or without metronidazole 10 mg/kg/dose IV three times daily (maximum 500 mg per dose) 1

Evidence Comparison and Clinical Pearls

• Vancomycin vs. Fidaxomicin: Both have similar clinical cure rates (>90%), but fidaxomicin is associated with significantly lower recurrence rates (15.4% vs. 25.3%) 3. This is particularly notable for non-NAP1 strains.

• Vancomycin Dosing: No significant difference in treatment outcomes between high-dose (>500 mg daily) and low-dose (≤500 mg daily) vancomycin for severe CDI, though there may be a trend toward lower recurrence rates with higher doses 4.

• Metronidazole Limitations: Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1.

• Risk Factors to Consider: Recent antibiotic use (especially clindamycin, fluoroquinolones, cephalosporins), age >65 years, recent hospitalization, inflammatory bowel disease, and immunosuppression 2.

• Supportive Care: Provide IV fluid replacement, correct electrolyte imbalances, and consider albumin supplementation in cases of severe hypoalbuminemia 2.

• Surgical Intervention: Consider colectomy in cases of colonic perforation, systemic inflammation not responding to antibiotics, toxic megacolon, or severe ileus. Surgery is recommended before serum lactate exceeds 5.0 mmol/L to reduce mortality 2.

• Prevention Strategies: Implement antibiotic stewardship to reduce unnecessary antibiotic use and practice good hand hygiene 2.