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

Treatment of Clostridioides difficile Infection (CDI)

For initial episodes of C. difficile infection, oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days are the preferred first-line treatments, with treatment selection based on disease severity and recurrence risk. 1, 2, 3

Classification of CDI Severity

Disease severity guides treatment selection:

• Non-severe CDI: No markers of severe colitis
• Severe CDI: One or more of the following:
  • WBC ≥15,000 cells/mm³
  • Serum creatinine ≥1.5 mg/dL
  • Evidence of severe colitis on imaging
  • Pseudomembranous colitis
• Fulminant CDI: Hypotension, shock, ileus, or megacolon

First-Line Treatment Recommendations

Initial Episode

1. Non-severe CDI:

   • Adults: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1, 2
   • Children: Oral vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days OR metronidazole 7.5 mg/kg/dose (max 500 mg) three times daily for 10 days 4

2. Severe CDI:

   • Adults: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1
   • Children: Oral vancomycin 10 mg/kg/dose (max 500 mg) four times daily for 10 days with or without IV metronidazole 4

3. Fulminant CDI:

   • Oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1
   • If ileus present: Add vancomycin enema 500 mg in 100 mL normal saline every 4-12 hours 4, 1

Important note: Metronidazole is no longer recommended as first-line therapy for adults with CDI according to recent guidelines, though it may still be used in specific circumstances such as mild-to-moderate disease in younger patients with limited risk factors for recurrence 2, 5, 3.

Treatment When Oral Therapy Is Not Possible

When patients cannot take oral medications:

• Intravenous metronidazole 500 mg three times daily for 10 days 4
• PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 4, 1
• AND/OR vancomycin 500 mg four times daily via nasogastric tube 4

Treatment of Recurrent CDI

1. First recurrence:

   • If initial episode was treated with metronidazole: Use vancomycin 125 mg four times daily for 10 days 4
   • If initial episode was treated with vancomycin: Use fidaxomicin 200 mg twice daily for 10 days 3

2. Second or subsequent recurrences:

   • Vancomycin in a tapered and pulsed regimen 4, 1
   • OR fidaxomicin 200 mg twice daily for 10 days 3
   • Consider adjunctive bezlotoxumab (monoclonal antibody against C. difficile toxin B) for patients with multiple risk factors for recurrence 5
   • Consider fecal microbiota transplantation (FMT) after failure of appropriate antibiotic treatments for at least two recurrences 1, 2, 5

Surgical Management

Surgical intervention (colectomy) should be considered in:

• Perforation of the colon
• Systemic inflammation not responding to antibiotic therapy
• Toxic megacolon
• Severe ileus 4, 1

Supportive Care

• Discontinue the inciting antibiotic if possible 4, 1
• Fluid and electrolyte replacement
• Albumin supplementation if severe hypoalbuminemia
• Avoid antiperistaltic agents and opiates 1

Prevention Strategies

• Contact precautions and hand hygiene with soap and water
• Environmental cleaning with hypochlorite agents or sporicidal products
• Antibiotic stewardship to minimize use of high-risk antibiotics (clindamycin, fluoroquinolones, cephalosporins) 1

Special Considerations

• Pediatric dosing: Adjust based on weight (see table in reference 4)
• Fidaxomicin: FDA-approved for patients 6 months and older 6
• Inflammatory bowel disease patients: May have atypical presentation and worse outcomes 1

The treatment landscape for CDI continues to evolve, with fidaxomicin gaining preference over vancomycin and metronidazole in recent guidelines due to lower recurrence rates, and promising developments in microbiome-based therapies 3.