What is the recommended treatment for Clostridium difficile infection?

Treatment of Clostridium difficile Infection

For initial episodes of Clostridium difficile infection (CDI), either vancomycin 125 mg orally four times daily or fidaxomicin 200 mg orally twice daily for 10 days is recommended as first-line therapy over metronidazole. 1, 2

Treatment Based on Disease Severity

Non-severe CDI

• Definition: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL
• First-line treatment:
  • Vancomycin 125 mg orally four times daily for 10 days, OR
  • Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Alternative (if access to vancomycin or fidaxomicin is limited):
  • Metronidazole 500 mg orally three times daily for 10 days 1
  • Note: Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

Severe CDI

• Definition: WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL
• 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 megacolon
• Treatment:
  • Vancomycin 500 mg orally four times daily, AND
  • Intravenous metronidazole 500 mg every 8 hours 1, 2
  • If ileus is present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as a retention enema 1

Treatment of Recurrent CDI

First Recurrence

• If metronidazole was used initially:
  • Vancomycin 125 mg orally four times daily for 10 days 1, 2
• If standard vancomycin was used initially:
  • Vancomycin in a tapered and pulsed regimen (e.g., 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, 3

Second or Subsequent Recurrence

• Options include:
  • Vancomycin in a 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 (after at least 2 recurrences with appropriate antibiotic treatment) 1, 2

Pediatric Treatment

• For children with non-severe CDI:
  • Vancomycin 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days, OR
  • Metronidazole 7.5 mg/kg/dose (maximum 500 mg) orally three or four times daily for 10 days 1, 2

Important Considerations

Discontinue Inciting Antibiotics

• Stop the inciting antibiotic agent(s) as soon as possible to reduce the risk of CDI recurrence 1

Monitoring Response

• Expect decreased stool frequency and improved consistency within 3 days of starting treatment 2
• If no improvement after 3-5 days, reassess severity and consider changing treatment approach

Avoid

• Antiperistaltic agents and opiates as they may mask symptoms and potentially worsen disease 2
• High-dose vancomycin (500 mg four times daily) has not shown superior efficacy compared to standard dose (125 mg four times daily) for non-fulminant CDI 4, 5

Surgical Considerations

• Early surgical consultation for patients with severe complications:
  • Perforation of the colon
  • Systemic inflammation not responding to antibiotics
  • Toxic megacolon or severe ileus
  • Elevated serum lactate 1, 2

Evidence Strength

• The recommendation for vancomycin or fidaxomicin over metronidazole is based on high-quality evidence 1
• Fidaxomicin has been shown to have similar clinical cure rates to vancomycin but with significantly lower recurrence rates (15.4% vs. 25.3%) 6
• For first recurrences, fidaxomicin has demonstrated lower second recurrence rates compared to vancomycin (19.7% vs. 35.5%) 3
• The efficacy of fecal microbiota transplantation for multiple recurrent CDI is supported by moderate quality evidence 1