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 both non-severe and severe CDI, with metronidazole no longer recommended as initial therapy. 1, 2
Treatment Selection Based on Severity
Non-Severe CDI (WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL):
- Fidaxomicin 200 mg orally twice daily for 10 days is preferred due to lower recurrence rates 1, 2
- Vancomycin 125 mg orally four times daily for 10 days is an appropriate alternative, particularly when fidaxomicin access is limited 1, 3
Severe CDI (WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL):
- Either vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1
- Higher vancomycin doses (500 mg four times daily) have not demonstrated improved clinical outcomes compared to standard dosing 1, 4
Critical Initial Steps
- Discontinue the inciting antibiotic immediately whenever possible, as this reduces recurrence risk 1, 2
- Start empiric therapy without waiting for laboratory confirmation when substantial diagnostic delay is expected or in fulminant cases 1, 2
Recurrent CDI Treatment
First Recurrence:
- Vancomycin 125 mg orally four times daily for 10 days if metronidazole was used initially 1, 2
- Fidaxomicin 200 mg twice daily for 10 days is preferred if vancomycin was used for the initial episode, given lower subsequent recurrence rates 1
- Prolonged tapered and pulsed vancomycin regimen is an alternative option 1
Second or Subsequent Recurrence:
- Vancomycin in a tapered and pulsed regimen 1, 2
- 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
- Fecal microbiota transplantation (FMT) is particularly effective and recommended after at least 2 recurrences have failed appropriate antibiotic treatment 2, 5
Special Situations: NPO Patients
For patients unable to take oral medications:
- Intravenous metronidazole 500 mg every 8 hours PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1, 2
- Intravenous vancomycin alone is completely ineffective for CDI as it is not excreted into the colon 2, 3
- Transition to oral vancomycin or fidaxomicin once oral intake is possible 1, 2
- Vancomycin enema dosing can range from 250-500 mg in 100-500 mL saline administered 2-4 times daily 2
Treatment Duration and Monitoring
- Standard treatment duration is 10 days for all regimens 1, 3, 6
- Extend to 14 days if clinical response is delayed 1, 2
- Do NOT perform a "test of cure" after treatment completion—this is not recommended 1, 2
- Monitor serum vancomycin concentrations in select patients with renal insufficiency, inflammatory bowel disease, or those receiving concomitant aminoglycosides, as systemic absorption can occur 3
Pediatric Considerations (6 Months to <18 Years)
Fidaxomicin dosing:
- Patients ≥12.5 kg who can swallow tablets: 200 mg orally twice daily for 10 days 6
- Patients ≥4 kg: Weight-based oral suspension twice daily for 10 days 6
Vancomycin dosing:
- 40 mg/kg/day divided into 3-4 doses for 7-10 days (maximum 2 g daily) 3
Critical Pitfalls to Avoid
Do NOT use metronidazole for severe or recurrent CDI—it has inferior cure rates compared to vancomycin and carries cumulative neurotoxicity risk with repeated courses 1, 2
Do NOT administer only intravenous vancomycin for CDI—it is completely ineffective as it does not reach the colonic lumen 1, 2, 3
Do NOT continue the inciting antibiotic—failure to discontinue it significantly increases recurrence risk 1, 2
Monitor elderly patients (>65 years) closely for nephrotoxicity during and after oral vancomycin therapy, even with normal baseline renal function 3
Recognize that approximately 20% of patients will experience recurrence, with higher risk in elderly patients and those requiring continued antibiotic therapy 2, 5