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 significantly 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
- Prolonged tapered and pulsed vancomycin regimen as an alternative 1
- Fidaxomicin 200 mg twice daily for 10 days if vancomycin was used for the initial episode 1, 5
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, 5
- Fecal microbiota transplantation (FMT) is particularly effective after multiple recurrences have failed appropriate antibiotic treatment 2, 6
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 as soon as oral intake becomes possible 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, 5
- Extend to 14 days if clinical response is delayed, particularly with metronidazole 2
- Monitor renal function during and after treatment in patients >65 years of age, as nephrotoxicity can occur with oral vancomycin 3
- Monitor serum vancomycin concentrations in patients with renal insufficiency, inflammatory bowel disease, or those receiving concomitant aminoglycosides, as systemic absorption can occur 3
Critical Pitfalls to Avoid
Do NOT use metronidazole for severe or recurrent CDI due to inferior cure rates compared to vancomycin and risk of cumulative neurotoxicity with repeated courses 1, 2
Do NOT administer only intravenous vancomycin for CDI treatment, as it does not reach therapeutic concentrations in the colon 1, 2, 3
Do NOT perform a "test of cure" after completing CDI treatment, as this is not recommended 1, 2
Do NOT continue the inciting antibiotic if clinically feasible to discontinue, as this substantially increases recurrence risk 1, 2
Do NOT use oral vancomycin or fidaxomicin for systemic infections, as these agents have minimal systemic absorption and are only effective for intestinal CDI 3, 5