What are the treatment options for Clostridioides difficile (C. diff) infections?

Treatment Options for Clostridioides difficile Infection

For C. difficile infections, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the recommended first-line treatments, with fidaxomicin being preferred for non-severe initial infections due to lower recurrence rates. 1

Initial Treatment Based on Severity

Non-severe CDI

• First-line options:
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Vancomycin 125 mg orally four times daily for 10 days 1
• Alternative option (only if above unavailable or in patients ≤65 years):
  • Metronidazole 500 mg orally three times daily for 10 days 1
  • Note: Metronidazole is no longer recommended as first-line therapy for adults 3

Severe CDI

Severe CDI is characterized by hypotension, shock, ileus, megacolon, WBC >12,000, or elevated creatinine.

• Treatment regimen:
  • Vancomycin 500 mg orally four times daily 1
  • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 4-12 hours 1
  • Consider adding IV metronidazole 500 mg every 8 hours 1

Treatment of Recurrent CDI

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days OR
• Fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1

Second or Subsequent Recurrence

• Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment for at least 2 recurrences 1, 4
• FMT shows 70-90% success rates in preventing further recurrences 1, 4
• Bezlotoxumab 10 mg/kg IV once during antibiotic administration may be considered as adjunctive therapy, particularly in immunocompromised patients 1

Pediatric Dosing

• For children ≥6 months weighing ≥12.5 kg who can swallow tablets: 200 mg fidaxomicin tablet twice daily for 10 days 2
• For children unable to swallow tablets or <12.5 kg: Weight-based dosing of fidaxomicin oral suspension 2:
  • 4 kg to <7 kg: 80 mg (2 mL) twice daily
  • 7 kg to <9 kg: 120 mg (3 mL) twice daily
  • 9 kg to <12.5 kg: 160 mg (4 mL) twice daily
  • ≥12.5 kg: 200 mg (5 mL) twice daily
• Alternative for children: Metronidazole 7.5 mg/kg/dose (maximum 500 mg) three or four times daily for 10 days 1

Infection Control Measures

• Discontinue the inciting antibiotic as soon as possible 1
• Hand hygiene with soap and water (not alcohol-based sanitizers) 1
• Contact precautions and isolation 1
• Thorough environmental cleaning 1

Monitoring and Management

• Expect improvement within 2-3 days of treatment initiation 1
• If no improvement within 48-72 hours, reassess severity and consider alternative treatments 1
• Monitor for peripheral neuropathy in patients on metronidazole 1
• Monitor renal function in patients >65 years on vancomycin 1

Treatment Considerations and Pitfalls

• Do not use probiotics for prevention of CDI 3
• Avoid broad-spectrum antibiotics when possible 1
• Recognize risk factors for severe disease: age >60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, and abnormal abdominal CT findings 1
• For fulminant CDI not responding to medical therapy, surgical consultation may be needed 4
• FMT should be considered particularly when traditional anti-CDI antibiotics are ineffective, especially in elderly patients who may not be surgical candidates 4