What is the first line treatment for an adult patient with Clostridioides difficile (C. difficile) infection?

First-Line Treatment for Clostridioides difficile Infection

For an initial episode of C. difficile infection in adults, either vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days should be used as first-line therapy. 1

Treatment Algorithm Based on Disease Severity

Initial Episode - Non-Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days 1
• The 2021 IDSA/SHEA focused update suggests fidaxomicin over vancomycin (conditional recommendation), but acknowledges vancomycin remains an acceptable alternative depending on available resources 1
• Non-severe disease is defined as: white blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1

Initial Episode - Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days 1
• Severe disease is defined as: white blood cell count ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 1, 2
• Both agents have strong/high quality evidence for severe disease 1

Initial Episode - Fulminant Disease

• Vancomycin 500 mg orally four times daily (higher dose than non-fulminant) 1
• If ileus present: add rectal vancomycin instillation AND intravenous metronidazole 500 mg every 8 hours 1, 3
• Fulminant disease is characterized by: hypotension, shock, ileus, or megacolon 1
• Obtain prompt surgical evaluation as early intervention reduces mortality 1

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic immediately as continued use decreases clinical response and increases recurrence rates 1

Metronidazole Is No Longer First-Line

• Metronidazole should only be used in settings where vancomycin or fidaxomicin access is limited, and only for non-severe disease 1
• The recommended dose is metronidazole 500 mg orally three times daily for 10 days 1
• Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 3
• Metronidazole has inferior clinical success rates compared to vancomycin, particularly in severe disease 1, 4, 5

Important Clinical Considerations

Fidaxomicin vs. Vancomycin

• Fidaxomicin demonstrates similar cure rates to vancomycin (87.7% vs 86.8%) but significantly lower recurrence rates (15.4% vs 25.3%, P=0.005) 1
• Fidaxomicin better preserves gut microbiota and has higher clinical cure rates when concomitant antibiotics cannot be discontinued 1
• The main limitation is cost, which is why vancomycin remains an acceptable alternative 1

Treatment Duration

• Standard treatment duration is 10 days for both vancomycin and fidaxomicin 1, 2, 6, 7
• Consider extending to 14 days in patients with delayed response, particularly those treated with metronidazole 1

Common Pitfalls to Avoid

• Do NOT perform test-of-cure after treatment completion, as C. difficile PCR can remain positive for weeks due to persistent colonization 2
• Do NOT use intravenous vancomycin for CDI treatment, as parenteral administration is not effective for intestinal infection 7
• Do NOT use antimotility agents without specific CDI therapy, as this has historically led to poor outcomes 1

Monitoring in Special Populations

• In patients >65 years old, monitor renal function during and after treatment as nephrotoxicity risk is increased 7
• Patients with inflammatory intestinal disorders may have significant systemic absorption of oral vancomycin and require serum concentration monitoring 7