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

First-Line Therapy

• Vancomycin 125 mg orally four times daily for 10 days is recommended as first-line treatment for initial CDI 3, 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred first-line option due to lower recurrence rates compared to vancomycin 1, 2, 4
• Both agents are equally effective for initial clinical cure, but fidaxomicin demonstrates superior prevention of recurrence 1, 2

Disease Severity Does Not Change Initial Antibiotic Choice

• Non-severe disease (WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL): Use vancomycin 125 mg four times daily OR fidaxomicin 200 mg twice daily for 10 days 1
• Severe disease (WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL): Use the same dosing—vancomycin 125 mg four times daily OR fidaxomicin 200 mg twice daily for 10 days 1, 2
• Vancomycin demonstrated 97% cure rates versus 76% for metronidazole in severe CDI 3, 1, 2

Metronidazole: Limited Role

• Metronidazole 500 mg orally three times daily for 10 days should only be used in resource-limited settings where vancomycin or fidaxomicin are unavailable, and only for non-severe disease 3, 2
• Metronidazole is inferior to vancomycin for clinical cure (72.7% vs 81.1%, P=0.02) 3
• Avoid repeated or prolonged metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 3, 1, 2

Fulminant/Complicated CDI

Severe-Complicated Disease Management

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily for fulminant CDI 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

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option 1, 2
• Alternative: Vancomycin tapered and pulsed regimen rather than standard 10-day course 2

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen: 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 1
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 1, 2

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic(s) as soon as possible—continued use decreases clinical response and increases recurrence rates 3, 1, 2

Special Considerations for Concomitant Antibiotics

• When patients require concomitant antibiotics for other infections during CDI treatment, fidaxomicin achieves 90.0% cure rates versus 79.4% for vancomycin (P=0.04) 5
• Concomitant antibiotic use is associated with lower cure rates (84.4% vs 92.6%) and extended time to resolution of diarrhea (97 vs 54 hours) 5
• Fidaxomicin demonstrates 12.3% fewer recurrences compared to vancomycin when concomitant antibiotics are used (16.9% vs 29.2%, P=0.048) 5

Medications to Avoid

• Avoid antiperistaltic agents and opiates in patients with CDI—historically associated with poor outcomes 3, 1

Empiric Treatment Indications

• Start antibiotic therapy empirically if substantial delay in laboratory confirmation is expected (>48 hours) or if fulminant CDI is present 3

Treatment Response and Monitoring

Expected Clinical Course

• Clinical response typically requires 3-5 days after starting therapy 1, 2
• Most patients resolve diarrhea within one week of treatment initiation 6
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those with continued antibiotic use 1, 2

Follow-Up Testing

• Do not perform a "test of cure" after treatment completion 1
• C. difficile organisms may persist in stool for weeks after successful treatment in approximately 50% of patients 6

Pediatric Considerations

Dosing for Children ≥6 Months

• Fidaxomicin is FDA-approved for pediatric patients aged 6 months and older 4
• Children ≥12.5 kg who can swallow tablets: 200 mg orally twice daily for 10 days 4
• Weight-based oral suspension dosing available for younger children or those unable to swallow tablets 4