Treatment of Clostridioides difficile Infection
For an initial episode of C. difficile infection, start either fidaxomicin 200 mg orally twice daily for 10 days (preferred) or vancomycin 125 mg orally four times daily for 10 days. 1
Initial Episode Treatment Algorithm
First-Line Therapy (Non-Severe and Severe Disease)
Fidaxomicin 200 mg orally twice daily for 10 days is the preferred treatment for both non-severe and severe initial CDI episodes, as it significantly reduces recurrence rates compared to vancomycin 1, 2, 3
Vancomycin 125 mg orally four times daily for 10 days remains an acceptable alternative with proven efficacy (81-92% clinical cure rates) 1, 4
The distinction between non-severe (WBC ≤15,000 cells/μL and serum creatinine <1.5 mg/dL) and severe disease (WBC ≥15,000 cells/μL or serum creatinine >1.5 mg/dL) does not change the initial antibiotic choice—both fidaxomicin and vancomycin are appropriate for either severity 1, 2
When Metronidazole May Be Considered
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 CDI 1
Metronidazole has inferior efficacy compared to vancomycin, particularly in severe cases (76% vs 97% cure rates in severe CDI) 2, 3
Avoid repeated or prolonged metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2, 3
Fulminant/Life-Threatening CDI
Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg every 8 hours is the regimen of choice for fulminant CDI (hypotension, shock, ileus, or megacolon) 1
If ileus is present, add vancomycin 500 mg in 100 mL normal saline per rectum every 6 hours as a retention enema 1, 2
Vancomycin can be administered via nasogastric tube if oral route is compromised 1, 2
Note: Intravenous vancomycin has no effect on CDI since it is not excreted into the colon 2
Critical Management Principles
Discontinue the inciting antibiotic agent(s) as soon as possible, as this reduces the risk of CDI recurrence 1, 2, 3
Avoid antiperistaltic agents and opiates in all patients with CDI 2, 3
Clinical response typically requires 3-5 days after starting therapy; median time to diarrhea resolution is 4-5 days 4, 5
Do not perform a "test of cure" after treatment completion 2
Common Pitfalls to Avoid
Do not use metronidazole for severe or fulminant CDI—it has significantly lower cure rates and is strongly discouraged in these settings 2
Do not use intravenous vancomycin alone for CDI treatment—it does not reach therapeutic concentrations in the colon 2
Do not continue unnecessary proton pump inhibitors, though insufficient evidence exists to mandate discontinuation solely for CDI prevention 1
Be aware that recurrence occurs in 18-25% of patients within 4 weeks after successful treatment with vancomycin 4
Why Fidaxomicin is Preferred
Fidaxomicin demonstrates significantly lower recurrence rates compared to vancomycin (13.3% vs 24.0% in per-protocol analysis) 6
The lower recurrence rate translates to better long-term outcomes and reduced need for additional treatment courses 1, 6
Clinical cure rates with fidaxomicin are non-inferior to vancomycin (92.1% vs 89.8%) 6
Implementation depends on available resources, as fidaxomicin is more expensive than vancomycin 1