Standard Treatment of Clostridioides difficile Infection in Adults
For initial C. difficile infection in adults, use oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days as first-line therapy, regardless of disease severity. 1, 2
Initial Episode Treatment
The Infectious Diseases Society of America guidelines have shifted away from metronidazole as first-line therapy. Both vancomycin and fidaxomicin are now equally recommended as first-line options for all initial episodes, whether non-severe or severe 1, 2. This represents a significant change from older recommendations that stratified treatment by severity.
Key dosing:
- Vancomycin: 125 mg orally four times daily for 10 days 1, 2, 3
- Fidaxomicin: 200 mg orally twice daily for 10 days 1, 3
Fidaxomicin demonstrates significantly lower recurrence rates (15% vs 25-31% with vancomycin), though cost may be prohibitive 1, 4. Both agents have equivalent cure rates of approximately 87-88% 4.
Critical first step: Immediately discontinue the causative antibiotic if clinically feasible, as this dramatically reduces recurrence risk 1, 2, 4.
Disease Severity Assessment
While treatment no longer differs by severity for initial episodes, severity assessment remains important for monitoring and prognosis:
- Non-severe: WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 2
- Severe: WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 2
- Fulminant: Hypotension, shock, ileus, or megacolon 2, 4
Fulminant/Complicated CDI
For fulminant disease, escalate to vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1, 2, 4. This higher vancomycin dose (500 mg vs 125 mg) is expert opinion-based, though 125 mg is non-inferior in uncomplicated disease 4.
If ileus is present, add vancomycin retention enema 500 mg in 100 mL normal saline every 6 hours 1, 2, 4. Rectal vancomycin should never be used alone, as it may not reach the entire affected colon 4.
Obtain prompt surgical consultation for fulminant cases, as early intervention reduces mortality 4. Subtotal or total colectomy with end ileostomy may be required 4.
Recurrent CDI Treatment
Approximately 20% of patients experience recurrence after initial treatment 1.
First recurrence:
- Preferred: Fidaxomicin 200 mg orally twice daily for 10 days 1
- Alternative: Vancomycin 125 mg four times daily for 10 days 1, 2
Second or subsequent recurrences:
- Tapered and pulsed vancomycin regimen: 125 mg every 6 hours for 1-2 weeks, then 125 mg every 12 hours for 1 week, then 125 mg every 24 hours for 1 week, then 125 mg every 48 hours for 2-8 weeks 4
- Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 1, 2
FMT demonstrates remarkable efficacy with 87-94% clinical resolution rates for recurrent CDI 4. One randomized trial showed 94% symptom resolution with vancomycin followed by FMT versus only 31% with vancomycin alone 4.
Critical Pitfalls to Avoid
- Never use intravenous vancomycin alone for CDI - it does not achieve adequate colonic concentrations 1
- Avoid metronidazole for severe or recurrent CDI - it has inferior efficacy (cure rates 66-73% vs 78-97% for vancomycin in severe disease) and risk of cumulative neurotoxicity 2, 4
- Do not use antiperistaltic agents or opiates in patients with active CDI 1
- Do not perform "test of cure" after treatment completion - testing should only be done in symptomatic patients 4, 1
- Failing to discontinue the inciting antibiotic dramatically increases recurrence risk 1, 2, 4
Special Situations
For patients unable to take oral medications (NPO or ileus):
- Intravenous metronidazole 500 mg every 8 hours PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1
- Transition to oral therapy once oral intake is possible 1
Treatment duration: Standard 10 days for all initial episodes and most recurrences, with consideration for extending to 14 days if delayed response 1, 2. Clinical response is expected within 3-5 days 4, 1.