What is the treatment for Clostridioides difficile (C diff) 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

Initial Episode Treatment Algorithm

First-Line Options

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred first-line treatment for both non-severe and severe CDI due to lower recurrence rates compared to vancomycin 1, 2
• Vancomycin 125 mg orally four times daily for 10 days is an equally effective alternative for initial clinical cure, though recurrence rates are higher 1, 2
• The 125 mg dose of vancomycin is as effective as higher doses (500 mg) for non-fulminant disease and should be used preferentially due to lower cost 3

Disease Severity Classification

• Non-severe disease: WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1
• Severe disease: WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 1
• Both severity categories can be treated with the same first-line regimens (vancomycin or fidaxomicin at standard doses) 1, 2

Fulminant/Complicated CDI

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily for patients with fulminant disease 2
• For patients unable to take oral medications: IV metronidazole 500 mg three times daily PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 2

Metronidazole Role

• Metronidazole is no longer preferred for initial treatment due to inferior efficacy, particularly in severe cases (76% cure rate vs. 97% with vancomycin) 1, 2
• May only be considered in resource-limited settings 2

Recurrent CDI Treatment Algorithm

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option, reducing second recurrence from 35.5% (with vancomycin) to 19.7% 1, 2, 4
• Vancomycin tapered and pulsed regimen is an alternative 2

Second and Subsequent Recurrences

Use vancomycin tapered and pulsed regimen 1, 2:

• 125 mg four times daily for 10-14 days
• Then 125 mg twice daily for 7 days
• Then 125 mg once daily for 7 days
• Then 125 mg every 2-3 days for 2-8 weeks

Fecal Microbiota Transplantation (FMT)

• Strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 1, 2

Critical Management Principles

What to Do

• Discontinue the inciting antibiotic(s) as soon as possible to reduce recurrence risk 1, 2
• Allow 3-5 days for clinical response after starting therapy 1, 2

What to Avoid

• Do NOT use antiperistaltic agents or opiates in patients with CDI 1
• Do NOT use repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2
• Do NOT perform a "test of cure" after treatment completion 1

Pediatric Dosing (6 Months to <18 Years)

• Fidaxomicin 200 mg orally twice daily for 10 days for patients ≥12.5 kg who can swallow tablets 5
• For younger or smaller children, weight-based oral suspension dosing ranges from 80 mg (4-7 kg) to 200 mg (≥12.5 kg) twice daily 5

Common Pitfalls

• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those requiring continued antibiotic use for other infections 1, 2
• Early recurrence (within 14 days) is significantly reduced with fidaxomicin compared to vancomycin (8% vs. 27%) 4
• The organism may persist in stool for weeks after treatment without clinical significance; do not retest 1