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

Treatment of Clostridioides difficile Infection

First-Line Treatment for Initial CDI Episode

Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the recommended first-line treatments for all initial episodes of C. difficile infection, regardless of severity. 1, 2

Treatment Selection

• Vancomycin 125 mg orally four times daily for 10 days is the standard first-line option 1, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is equally effective for initial treatment and associated with lower recurrence rates 1, 4
• Both agents are appropriate for non-severe CDI (WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL) and severe CDI (WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL) 1

Critical Action

• Discontinue the inciting antibiotic immediately to reduce recurrence risk 1, 2

Important Dosing Considerations

• Higher vancomycin doses (500 mg four times daily) do not improve clinical outcomes compared to standard 125 mg dosing for severe CDI 1, 5
• Standard treatment duration is 10 days, but may extend to 14 days if clinical response is delayed 1, 2

Recurrent CDI Treatment

First Recurrence

• If metronidazole was used initially: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• If vancomycin was used initially: Fidaxomicin 200 mg twice daily for 10 days OR prolonged tapered and pulsed vancomycin regimen 1

Second or Subsequent Recurrence

Treatment options include: 1, 2

• Vancomycin in a tapered and pulsed regimen
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days
• Fidaxomicin 200 mg twice daily for 10 days
• Fecal microbiota transplantation is particularly effective after at least 2 recurrences that have failed appropriate antibiotic treatment 2, 6

NPO Patients or Severe/Fulminant CDI

For patients unable to take oral medications, use combination therapy: 1, 2

• Intravenous metronidazole 500 mg every 8 hours PLUS
• Vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1, 2
• Transition to oral vancomycin or fidaxomicin once oral intake is possible 2

Critical Caveat

• Intravenous vancomycin alone is completely ineffective for CDI as it is not excreted into the colon 2, 3, 7
• Oral vancomycin must be used; parenteral vancomycin does not treat CDI 3

Common Pitfalls to Avoid

Metronidazole Use

• Do not use metronidazole for initial treatment, severe CDI, or recurrent CDI due to inferior cure rates compared to vancomycin (72.7% vs 81.1% clinical success) 1, 8
• Metronidazole is particularly inferior in severe CDI (66.3% vs 78.5% with vancomycin) 8
• Avoid repeated or prolonged metronidazole courses due to cumulative neurotoxicity risk 1, 2

Other Critical Errors

• Never perform a "test of cure" after treatment completion - this is not recommended 1, 2
• Do not fail to discontinue the inciting antibiotic - this significantly increases recurrence risk 1, 2
• Do not use only IV vancomycin - it provides no colonic drug levels 2, 3

Special Monitoring Considerations

Nephrotoxicity Risk

• Monitor renal function during and after treatment, especially in patients >65 years of age 3
• Nephrotoxicity can occur during or after completion of oral vancomycin therapy 3
• Consider monitoring serum vancomycin concentrations in patients with renal insufficiency, colitis, or those receiving concomitant aminoglycosides 3

Systemic Absorption

• Clinically significant serum concentrations can occur with oral vancomycin in patients with inflammatory intestinal disorders 3
• Faecal vancomycin levels are proportional to dose administered and remain well above MIC90 even with standard dosing 9