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

Treatment of Clostridioides difficile Colitis

For C. difficile colitis, oral fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment due to its superior clinical outcomes and lower recurrence rates compared to other antibiotics. 1

Disease Severity Assessment

Severity of C. difficile infection (CDI) should be determined to guide appropriate treatment:

Non-severe CDI (all criteria must be met):

• Stool frequency <4 times daily
• No signs of severe colitis
• No markers of severe systemic inflammatory response

Severe CDI (one or more present):

• Fever (core body temperature >38.5°C)
• Hemodynamic instability or signs of septic shock
• Peritonitis signs (decreased bowel sounds, abdominal tenderness)
• Ileus signs (vomiting, absent stool passage)
• Marked leukocytosis (>15 × 10^9/L)
• Marked left shift (band neutrophils >20%)
• Serum creatinine rise (>50% above baseline)
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Imaging findings: distended large intestine, colonic wall thickening, pericolonic fat stranding

Treatment Algorithm

Initial Episode

When oral therapy is possible:

• Non-severe CDI:

  • First choice: Fidaxomicin 200 mg twice daily for 10 days 1, 2
  • Alternative: Vancomycin 125 mg four times daily for 10 days 3, 4
  • If above unavailable: Metronidazole 500 mg three times daily for 10 days 3

• Severe CDI:

  • First choice: Fidaxomicin 200 mg twice daily for 10 days 1
  • Alternative: Vancomycin 125 mg four times daily for 10 days 3, 4

When oral therapy is impossible:

• Non-severe CDI:

  • Metronidazole 500 mg three times daily intravenously for 10 days 3

• Severe CDI with ileus:

  • Metronidazole 500 mg three times daily intravenously for 10 days PLUS
  • Vancomycin 500 mg four times daily by nasogastric tube AND/OR
  • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours as retention enema 3, 1

Recurrent Episodes

• 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
  • Alternative: Same treatment as initial episode if disease severity unchanged 3

• Second or subsequent recurrences:

  • Vancomycin 125 mg four times daily for at least 10 days with taper/pulse strategy (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 3, 1
  • Consider fecal microbiota transplantation after failure of appropriate antibiotic treatments 1

Important Considerations

Avoid These Medications

• Antiperistaltic agents and opiates should be avoided as they can worsen the condition 3
• Unnecessary antibiotics should be discontinued to reduce recurrence risk 1
• Consider discontinuing proton pump inhibitors if not clinically indicated 1

Surgical Intervention

Colectomy should be performed in any of these situations:

• Perforation of the colon
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
• Toxic megacolon or severe ileus
• Serum lactate >5.0 mmol/L (indicates need for urgent surgery) 3

Monitoring Response

• Treatment response is defined as decreased stool frequency or improved stool consistency after 3 days and no new signs of severe colitis 3
• Treatment failure is defined as absence of treatment response 3
• Monitor patients for at least 8 weeks after treatment to assess for recurrence 1

Common Pitfalls to Avoid

1. Testing asymptomatic patients - Only test unformed stool samples from symptomatic patients with ≥3 unformed stools in 24 hours 1, 5

2. Inadequate treatment duration - Complete the full course of antibiotics even if symptoms improve 2

3. Delayed surgical consultation - Early surgical evaluation is crucial in fulminant disease; mortality increases with delayed intervention 1, 6

4. Failure to recognize severe disease - Promptly escalate therapy when markers of severe disease are present 3

5. Inappropriate antibiotic stewardship - Unnecessary antibiotics increase recurrence risk; discontinue inciting antibiotics when possible 3, 1