What is the treatment for Clostridium difficile infection?

Treatment of Clostridioides difficile Infection

For initial C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days, with fidaxomicin preferred due to significantly lower recurrence rates. 1, 2, 3

Initial Episode Treatment by Severity

Non-Severe CDI (WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL)

• First-line options: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1, 2, 3
• Fidaxomicin is preferred when available due to lower recurrence rates (approximately 15% vs 25% with vancomycin) 4, 5
• Metronidazole 500 mg three times daily for 10 days is NO LONGER recommended as first-line therapy, though may be considered in resource-limited settings 3, 6

Severe CDI (WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL)

• First-line options: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1, 2, 3
• Vancomycin demonstrated superior cure rates compared to metronidazole in severe disease (97% vs 76%) 2, 3
• Higher doses of vancomycin (500 mg four times daily) do NOT improve outcomes compared to standard dosing 1

Fulminant CDI (Hypotension, shock, ileus, or megacolon)

• Oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1, 3
• If ileus is present, add rectal vancomycin instillation (500 mg in 100 mL normal saline every 4-12 hours) 1, 3
• Consider vancomycin administration via nasogastric tube if oral route compromised 1
• Surgical consultation should occur early—colectomy indicated for perforation, toxic megacolon, or deterioration despite maximal medical therapy 1

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days is the preferred option 1, 2, 3
• Alternative: Tapered and pulsed vancomycin regimen (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) 1, 2, 3
• If metronidazole was used initially, switch to standard vancomycin 125 mg four times daily for 10 days 1
• Fidaxomicin reduced recurrence rates by approximately 50% compared to vancomycin in first recurrence patients (19.7% vs 35.5%) 4

Second or Subsequent Recurrence

• Vancomycin tapered and pulsed regimen (as described above) 1, 2, 3
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Fidaxomicin 200 mg twice daily for 10 days 1, 2
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences (i.e., after 3 total CDI episodes) that have failed appropriate antibiotic treatments 1, 2, 3, 6

Critical Management Principles

Antibiotic Stewardship

• Discontinue the inciting antibiotic(s) immediately whenever possible 1, 2, 3
• In mild CDI clearly induced by antibiotics, discontinuation alone with close observation may be acceptable, but start treatment immediately if deterioration occurs 1
• When concomitant antibiotics are necessary for other infections, fidaxomicin is superior to vancomycin (90.0% vs 79.4% cure rate) 7

Medications to Avoid

• Avoid antiperistaltic agents and opiates, especially in acute setting, as they may worsen outcomes 1, 2, 3
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 2, 3
• Proton pump inhibitors should ideally be discontinued when possible, though evidence for benefit is limited 1

Treatment Duration and Monitoring

• Standard treatment duration is 10 days, though may extend to 14 days in patients with delayed response (particularly with metronidazole) 1
• Clinical response typically requires 3-5 days after starting therapy 2, 3
• Do NOT perform a "test of cure" after treatment completion—testing should only occur if symptoms persist or recur 2
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those requiring continued antibiotic use 2, 3

Common Pitfalls to Avoid

• Do not use metronidazole for severe CDI—it has significantly lower cure rates than vancomycin 2, 3
• Do not use intravenous vancomycin alone—it does not achieve adequate colonic concentrations 1
• Do not delay surgical consultation in fulminant cases—operate before serum lactate exceeds 5.0 mM when possible 1
• Do not continue the same antibiotic regimen for multiple recurrences—escalate to tapered/pulsed vancomycin or FMT 1, 2