Outpatient Treatment of Clostridioides difficile Infection
For outpatient treatment of C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days as first-line therapy, with fidaxomicin preferred due to lower recurrence rates. 1, 2, 3, 4
Initial Episode Treatment
First-Line Antibiotic Options
- Vancomycin 125 mg orally four times daily for 10 days is the standard dose for both non-severe and severe initial C. difficile infection 1, 2, 3
- Fidaxomicin 200 mg orally twice daily for 10 days is equally effective for initial cure but demonstrates significantly lower recurrence rates, making it the preferred option when available 1, 2, 4
- Metronidazole is no longer recommended for initial treatment due to inferior efficacy compared to vancomycin, particularly in severe cases, and should only be considered in resource-limited settings 2, 5, 6
Critical Management Principles
- Discontinue the inciting antibiotic immediately if clinically feasible, as this significantly reduces recurrence risk 1, 2
- Never use intravenous vancomycin for C. difficile infection—it is completely ineffective as it does not reach the colonic lumen 1, 3
- Avoid antiperistaltic agents and opiates entirely as they worsen outcomes and increase complications 1, 2
First Recurrence Treatment
Antibiotic Selection Strategy
- If metronidazole was used initially: Use vancomycin 125 mg four times daily for 10 days 7, 1
- If standard vancomycin was used initially: Use a prolonged tapered and pulsed vancomycin regimen:
- Fidaxomicin 200 mg twice daily for 10 days is preferred for first recurrence due to demonstrated lower rates of subsequent recurrence 7, 2
Multiple Recurrences (≥2 Episodes)
Treatment Escalation
- Vancomycin tapered and pulsed regimen (as detailed above) if not previously used 7
- Fidaxomicin extended regimen: 200 mg twice daily for 5 days, then 200 mg every other day for 20 days (days 7-25) 7
- Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 2, 5
Severe Disease Indicators
When to Escalate Care
Severe C. difficile infection is defined by any of the following 7:
- Age >65 years
- White blood cell count ≥15,000 cells/mL
- Serum creatinine >1.5 mg/dL or ≥50% increase from baseline
- Body temperature >38.5°C
- ≥10 bowel movements within 24 hours
- Severe abdominal pain
- Albumin <2.5 mg/dL
- Active malignancy
For severe disease in the outpatient setting, use the same vancomycin dose (125 mg four times daily for 10 days) but consider closer monitoring or hospitalization 1, 2
Fulminant Disease (Requires Hospitalization)
If any of the following develop, immediate hospitalization is required 7:
- Hypotension or shock
- Ileus or toxic megacolon
- End-organ failure
- Colonic perforation
Treatment: Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1, 2
Pediatric Dosing (≥6 months of age)
- Non-severe CDI: 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days 1, 3
- Severe/fulminant CDI: 10 mg/kg/dose (maximum 500 mg) orally every 8 hours for 10 days 1
- Fidaxomicin: Weight-based dosing for patients ≥4 kg, 40 mg/mL oral suspension twice daily for 10 days 4
Common Pitfalls to Avoid
- Do not use metronidazole for recurrent CDI due to lower sustained response rates and risk of cumulative neurotoxicity with repeated courses 7, 2
- Do not extend treatment duration beyond 10 days for initial episodes unless there is delayed clinical response 7
- Do not test for cure—clinical response typically requires 3-5 days, and repeat testing is not indicated if symptoms resolve 2
- Monitor renal function in patients >65 years as nephrotoxicity can occur with oral vancomycin, particularly in elderly patients 3