What is the treatment for Clostridioides difficile (Cdiff) symptoms?

Treatment of Clostridioides difficile Infection (CDiff) Symptoms

Oral vancomycin 125 mg four times daily for 10 days is the recommended first-line therapy for both non-severe and severe Clostridioides difficile infection. 1

Disease Severity Classification

• CDiff infection should be classified based on severity to guide appropriate treatment:
  • Non-severe CDI: Leukocyte count <15,000 cells/mL, serum creatinine <1.5 mg/dL, stool frequency <4 times daily, and no signs of severe colitis 1, 2
  • Severe CDI: Leukocyte count ≥15,000 cells/mL, serum creatinine ≥1.5 mg/dL, temperature >38.5°C, hemodynamic instability, or evidence of pseudomembranous colitis 1, 2
  • Fulminant CDI: Hypotension, shock, ileus, or megacolon 3, 1

Treatment Algorithm Based on Disease Severity

Non-Severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days 3, 1, 2
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days, especially for patients at high risk of recurrence 1, 4
• Less preferred alternative: Oral metronidazole 500 mg three times daily for 10 days (only if access to vancomycin or fidaxomicin is limited) 3, 2

Severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days 3, 1, 2
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 1, 4

Fulminant CDI

• Oral vancomycin 500 mg four times daily for 10 days 3, 2
• PLUS intravenous metronidazole 500 mg every 8 hours 3
• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 3, 2
• Consider surgical consultation for patients with toxic megacolon, perforation, or severe ileus 1

Treatment of Recurrent CDI

• First recurrence: Treat based on severity using the algorithm above 1, 2
• Second recurrence: 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) 3, 1
• Multiple recurrences: Consider fecal microbiota transplantation after appropriate antibiotic treatment 3, 1, 5

Important Clinical Considerations

• Discontinue the inciting antibiotic as soon as possible to reduce the risk of CDI recurrence 1, 2
• Avoid antimotility agents such as loperamide and opiates, especially in the acute setting 2
• Consider discontinuing proton pump inhibitors in patients at high risk for CDI 1
• Ensure proper hand hygiene with soap and water, as alcohol-based hand sanitizers are ineffective against C. difficile spores 1

Pediatric Considerations

• For children with non-severe CDI: Metronidazole (7.5 mg/kg/dose, max 500 mg) three times daily or vancomycin (10 mg/kg/dose, max 125 mg) four times daily for 10 days 3
• For children with severe or fulminant CDI: Vancomycin (10 mg/kg/dose, max 500 mg) orally or rectally every 8 hours, with or without metronidazole IV for 10 days 3
• For recurrent CDI in children: Consider vancomycin extended regimen or fecal microbiota transplantation 3

Common Pitfalls to Avoid

• Failing to assess disease severity before selecting treatment 2
• Continuing unnecessary antibiotics that may have triggered the CDI 1, 2
• Using metronidazole for severe CDI, which has higher failure rates 3, 6
• Prolonged or repeated courses of metronidazole due to risk of neurotoxicity 2
• Inadequate treatment duration (should be at least 10 days) 1

Fidaxomicin is now recommended by many experts as an alternative first-line therapy due to its microbiome-sparing properties and reduced risk of recurrence compared to vancomycin, particularly in patients at high risk for recurrent infection 7.