What is the recommended treatment for outpatient Clostridioides (C.) difficile infection?

Treatment of Outpatient Clostridioides difficile Infection

For outpatient Clostridioides difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the recommended first-line treatments, with metronidazole now considered only as an alternative option for non-severe cases. 1, 2

Treatment Based on Disease Severity

Non-severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days 1, 2
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 1, 2
• Alternative (if access to vancomycin or fidaxomicin is limited): Oral metronidazole 500 mg three times daily for 10 days 1, 3

Severe CDI

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

Criteria for Determining Severe CDI

• Leukocytosis (WBC >15 × 10^9/L) 2
• Serum albumin <30 g/L 2
• Rise in serum creatinine (≥133 μM or ≥1.5 times premorbid level) 2
• Advanced age and significant comorbidities 2
• Other signs: fever >38.5°C, rigors, hemodynamic instability, signs of peritonitis or ileus 1

Treatment of Recurrent CDI

First Recurrence

• Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 1

Second or Subsequent Recurrences

• Oral vancomycin 125 mg four times daily for at least 10 days, followed by a tapered and pulsed regimen 1
• Alternative: Oral vancomycin for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 1
• For multiple recurrences that have failed appropriate antibiotic treatments: Fecal microbiota transplantation 1

Important Considerations

Antibiotic Stewardship

• Discontinue the inciting antibiotic if possible, as continued use significantly increases risk of recurrence 1, 2
• If antibiotics must be continued, use those less frequently implicated with CDI (parenteral aminoglycosides, sulfonamides, macrolides, tetracyclines) 1

Supportive Measures

• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 1, 3
• Consider albumin supplementation in patients with severe hypoalbuminemia (<2 g/dL) 1
• Correct fluid and electrolyte imbalances promptly 1

Infection Control

• Hand hygiene with soap and water (not alcohol-based sanitizers) as alcohol does not kill C. difficile spores 2
• Patients with known or suspected CDI should ideally be placed in a private room with en suite facilities 1

Common Pitfalls to Avoid

• Metronidazole should not be used for long-term therapy due to potential for cumulative neurotoxicity 1
• Repeated or prolonged courses of metronidazole should be avoided 1
• Proton pump inhibitors (PPIs) may increase risk of CDI; discontinue unneeded PPIs 1
• Do not rely on alcohol-based hand sanitizers for C. difficile prevention 2

Special Populations

• For children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors 4
• Pediatric dosing for oral vancomycin: 10 mg/kg/dose four times daily (maximum 125 mg per dose) 1

The shift away from metronidazole as first-line therapy represents an important change in recent guidelines, with both vancomycin and fidaxomicin showing superior outcomes, particularly for reducing recurrence rates 5.