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

Treatment of Clostridioides difficile Colitis

For C. difficile colitis, treatment should be based on disease severity, with metronidazole for non-severe cases and vancomycin for severe cases, while fidaxomicin is an effective alternative with lower recurrence rates. 1, 2

Disease Severity Assessment

Disease severity guides treatment selection:

• Non-severe C. diff infection:

  • Stool frequency < 4 times daily
  • No signs of severe colitis
  • WBC < 15 × 10^9/L
  • Normal serum albumin and creatinine 1, 2

• Severe C. diff infection (one or more of):

  • Fever > 38.5°C
  • Marked leukocytosis (WBC > 15 × 10^9/L)
  • Serum albumin < 30 g/L
  • Rise in serum creatinine (≥1.5 times baseline)
  • Hemodynamic instability
  • Signs of peritonitis or ileus
  • Pseudomembranous colitis on endoscopy 1, 3

Initial Treatment Based on Disease Severity

For Non-Severe CDI:

• First-line: Metronidazole 500 mg orally three times daily for 10 days 1
• Alternative: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 2, 4

For Severe CDI:

• First-line: Vancomycin 125 mg orally four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 2, 3

When Oral Therapy Is Not Possible:

• Non-severe: Metronidazole 500 mg intravenously three times daily for 10 days 1
• Severe: Metronidazole 500 mg intravenously three times daily for 10 days PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours AND/OR vancomycin 500 mg four times daily by nasogastric tube 1

Management of Recurrent CDI

• First recurrence: Treat as initial episode based on severity 1, 2

  • Consider vancomycin or fidaxomicin instead of metronidazole even for non-severe cases 3

• Second and subsequent recurrences:

  • Vancomycin 125 mg orally four times daily for at least 10 days 1
  • Consider vancomycin taper/pulse strategy (decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 1, 3
  • Fidaxomicin may be considered due to lower recurrence rates 1, 4
  • For multiple recurrences, fecal microbiota transplantation (FMT) should be considered 5, 6

Surgical Management

Surgical consultation should be obtained for patients with:

• Perforation of the colon
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
• Toxic megacolon or severe ileus 1

Surgery should be performed before colitis becomes very severe, ideally before serum lactate exceeds 5.0 mmol/L 1

Important Adjunctive Measures

• Discontinue the inciting antibiotic if clinically possible 2, 3
• Avoid antiperistaltic agents and opiates as they may mask symptoms and potentially worsen disease 1
• Implement infection control measures including hand hygiene with soap and water (not alcohol-based sanitizers) 2, 3
• For patients at high risk of recurrence, consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) 3, 6

Monitoring Response

• Monitor for clinical response (decreased stool frequency, improved stool consistency) within 3 days of treatment initiation 2
• Treatment failure is defined as absence of improvement after 3-5 days 2, 3
• No follow-up stool testing is needed if symptoms resolve 2

Special Considerations

• In critically ill patients with severe or fulminant CDI not responding to standard therapy, early consideration of surgical options or FMT may be warranted 5, 7
• Patients with inflammatory bowel disease represent a high-risk group for CDI and may require more aggressive initial therapy 8
• Fidaxomicin has been shown to have lower recurrence rates compared to vancomycin, which may be particularly beneficial in high-risk patients 1, 4