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

Treatment of Clostridioides difficile Infection (CDI)

For C. difficile diarrhea, oral vancomycin or fidaxomicin are the first-line treatments, with therapy selection based on disease severity, with metronidazole now considered inferior and reserved only for limited situations. 1

Disease Severity Classification

Disease severity guides treatment selection:

• Non-severe CDI: WBC ≤15,000 cells/μL and serum creatinine <1.5 mg/dL
• Severe CDI: WBC ≥15,000 cells/μL or serum creatinine >1.5 mg/dL
• Fulminant CDI: Hypotension, shock, ileus, or toxic megacolon 1, 2

First-Line Treatment Algorithm

Initial Episode

1. Non-severe CDI:

   • First choice: Oral vancomycin 125 mg four times daily for 10 days 2, 1
   • Alternative first choice: Fidaxomicin 200 mg twice daily for 10 days 1, 3
   • If access to first-line agents is limited: Metronidazole 500 mg three times daily for 10 days 2

2. Severe CDI:

   • Oral vancomycin 125 mg four times daily for 10 days 2, 1
   • Fidaxomicin 200 mg twice daily for 10 days 1

3. Fulminant CDI or when oral therapy not possible:

   • Intravenous metronidazole 500 mg three times daily 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 2

Recurrent CDI Treatment

1. First recurrence:

   • Preferred: Fidaxomicin 200 mg twice daily for 10 days 1
   • Alternative: Vancomycin 125 mg four times daily for 10 days 2, 1

2. Second or subsequent recurrences:

   • Vancomycin in a tapered and pulsed regimen (e.g., decreasing daily dose with 125 mg every 3 days) 2
   • Consider bezlotoxumab 10 mg/kg IV once during antibiotic treatment for patients with risk factors for recurrence (age >65 years, immunocompromised, severe CDI) 1
   • Fecal microbiota transplantation (FMT) after at least 2-3 recurrences with appropriate antibiotic treatment failures 2, 1

Special Considerations

When Oral Therapy Not Possible

• Intravenous metronidazole 500 mg three times daily PLUS
• Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 2

Surgical Intervention

Consider colectomy for:

• Perforation of the colon
• Systemic inflammation not responding to antibiotic therapy
• Toxic megacolon or severe ileus
• Serum lactate >5.0 mmol/L 2

Important Adjunctive Measures

1. Discontinue the inciting antibiotic if possible 2
2. Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 2
3. Implement infection control measures:
   • Isolate patients with suspected or confirmed CDI
   • Hand hygiene with soap and water (alcohol-based sanitizers don't kill C. difficile spores)
   • Environmental cleaning with sporicidal agents 2, 1
4. Consider discontinuing proton pump inhibitors if not medically necessary 2

Common Pitfalls to Avoid

1. Do not use metronidazole as first-line therapy for adults with CDI as recent guidelines have downgraded its role due to inferior efficacy 1, 4
2. Do not repeat testing for cure if symptoms resolve 1
3. Do not use antiperistaltic agents during active infection 2
4. Do not use alcohol-based hand sanitizers alone for hand hygiene when caring for CDI patients 2
5. Do not use probiotics as primary prevention for CDI as evidence is insufficient 5

Monitoring and Follow-up

• Monitor patients for symptom resolution
• Follow patients for at least 8 weeks after treatment to assess for recurrence 1
• Recurrence typically occurs within 1-8 weeks after completing initial therapy 6

The treatment landscape for C. difficile has evolved significantly in recent years, with vancomycin and fidaxomicin now firmly established as first-line agents, replacing metronidazole which was previously the mainstay of therapy 4, 7. For patients with multiple recurrences, FMT has emerged as a highly effective option with cure rates of 80-90% 1.