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

Treatment of Clostridioides difficile Infection

Fidaxomicin 200 mg orally twice daily for 10 days is the preferred first-line treatment for patients with an initial episode of Clostridioides difficile infection (CDI), with oral vancomycin 125 mg four times daily for 10 days as an acceptable alternative. 1

Initial CDI Episode Treatment

Non-severe CDI

• First-line: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Alternative: Vancomycin 125 mg orally four times daily for 10 days 1, 3
• If oral therapy is not possible: Metronidazole 500 mg IV three times daily for 10 days 1

Severe CDI

• First-line: Vancomycin 125 mg orally four times daily for 10 days 4, 1
• For fulminant CDI: Vancomycin 500 mg four times daily orally or via nasogastric tube PLUS metronidazole 500 mg IV three times daily 1
• Surgical consultation for possible colectomy in cases of perforation, systemic inflammation, toxic megacolon, severe ileus, or serum lactate > 5.0 mmol/L 1

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days 4, 1
• OR Vancomycin in a tapered and pulsed regimen 4, 1
• OR Vancomycin 125 mg four times daily for 10 days (if metronidazole was used for initial episode) 4

Multiple Recurrences (≥2)

• Vancomycin in a tapered and pulsed regimen 4, 1
• OR Standard course of oral vancomycin followed by rifaximin 4
• OR Fidaxomicin 4
• Fecal microbiota transplantation (FMT) after appropriate antibiotic treatments have failed 4, 1

Pediatric Treatment (6 months to <18 years)

• First-line: Fidaxomicin (FDA-approved for ≥6 months) 1, 2
• Alternative: Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 4, 1
• For non-severe initial episode: Metronidazole or vancomycin for 10 days 4

Important Treatment Considerations

1. Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1
2. Avoid antiperistaltic agents and opiates to prevent worsening of disease 1
3. Disease severity assessment is critical for treatment selection:
   • Non-severe: <4 bowel movements/day, no signs of severe colitis
   • Severe: Temperature >38.5°C, leukocytosis >15,000/mm³, serum creatinine rise >50% above baseline, pseudomembranous colitis on endoscopy, or signs of severe colitis on imaging 1
4. Monitor treatment response after at least 3 days of therapy 1
5. For patients >65 years, monitor renal function during and after treatment with vancomycin 3

Common Pitfalls to Avoid

• Using metronidazole as first-line therapy for severe CDI (lower efficacy) 1
• Failure to recognize fulminant CDI requiring urgent intervention 1
• Overuse of FMT before trying appropriate antibiotic regimens 1
• Inadequate screening of FMT donors for transmissible pathogens 1
• Insufficient duration of therapy 1
• Using oral vancomycin for infections other than CDI or staphylococcal enterocolitis 3

Evidence Considerations

The recommendation for fidaxomicin as first-line therapy is supported by its similar efficacy to vancomycin with potentially lower recurrence rates 1, 5. While earlier guidelines and studies supported vancomycin 125 mg four times daily as standard therapy 4, 6, more recent evidence favors fidaxomicin for initial episodes 1. Both medications are FDA-approved for CDI treatment 3, 2, with fidaxomicin now approved for pediatric patients ≥6 months of age 2.

Higher doses of vancomycin (500 mg four times daily) have not shown significant benefits over the standard 125 mg dose for non-fulminant CDI 7, 8, 6, supporting the use of the lower dose except in fulminant cases.