Treatment of Clostridioides difficile Infection
For a first episode of 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; metronidazole is no longer recommended as preferred treatment. 1, 2
Disease Severity Assessment
Severity classification determines treatment intensity and is based on specific laboratory parameters:
- Non-severe CDI: WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1
- Severe CDI: WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 1
- Fulminant CDI: Presence of hypotension, shock, ileus, or megacolon 1
First Episode Treatment
Non-Severe and Severe Disease
Both severity categories receive the same initial therapy:
- Vancomycin 125 mg orally four times daily for 10 days (strong recommendation, high-quality evidence) 1
- Fidaxomicin 200 mg orally twice daily for 10 days (equally recommended first-line option with lower recurrence rates but substantially higher cost) 1, 3, 4
- Metronidazole 500 mg orally three times daily for 10 days should only be used when vancomycin or fidaxomicin are unavailable, as cure rates are inferior (84% vs 97% overall; 76% vs 97% in severe disease) 2
Fulminant Disease
Escalate therapy immediately for patients with hypotension, shock, ileus, or megacolon:
- Vancomycin 500 mg orally four times daily (high-dose) 1
- PLUS intravenous metronidazole 500 mg every 8 hours (strong recommendation, moderate-quality evidence) 1, 5
- If ileus is present, consider adding rectal vancomycin in combination with IV metronidazole and oral vancomycin 2, 5
First Recurrence Management
For patients who experience a first recurrence after successful initial treatment:
- Vancomycin taper-pulse regimen (specific dosing varies but typically involves gradual dose reduction over weeks) 6
- Fidaxomicin 200 mg twice daily for 10 days (preferred due to superior sustained response rates of 70-72% vs 57% with vancomycin) 3, 6
- Bezlotoxumab (intravenous monoclonal antibody) can be added to antibiotic therapy to prevent subsequent recurrences 7, 6
Multiple Recurrences
After second or subsequent recurrences:
- Fecal microbiota transplantation (FMT) is now clearly indicated for second CDI recurrence 7, 6
- FDA-approved live biotherapeutics are available for prevention of recurrent CDI (not limited to multiply recurrent cases) 6
- Fidaxomicin remains an option if FMT or live biotherapeutics are not accessible 6
Special Populations
Pregnancy
- Oral vancomycin is preferred as it has minimal systemic absorption 2
- Metronidazole can be used if necessary, though lower doses are preferred to minimize fetal exposure 2
Severe Renal Impairment
- Oral vancomycin dosing does not require adjustment as systemic absorption is minimal 1
- Fidaxomicin has no dosage adjustment requirements for renal impairment 3
- IV metronidazole should be used cautiously and for limited duration due to neurotoxicity risk 2, 5
Critical Management Principles
Immediate Actions
- Discontinue the inciting antibiotic immediately if clinically feasible, as this significantly reduces recurrence risk (strong recommendation, moderate-quality evidence) 1
- Avoid antiperistaltic agents and opiates entirely, as they worsen outcomes and increase complications 1
Metronidazole Safety Warning
- Never use metronidazole for more than 14 days or for multiple treatment courses due to cumulative and potentially irreversible neurotoxicity 2, 5
- Repeated or prolonged courses beyond 14 days carry significant risk of permanent neurological damage 2, 5
Fidaxomicin Advantages
- Sustained clinical response rates at 25 days post-treatment are significantly higher (70-72%) compared to vancomycin (57%) 3
- Lower recurrence rates are due to minimal impact on normal fecal microflora and narrow spectrum targeting C. difficile 4, 8
- Clinical cure rates at end of treatment are noninferior to vancomycin (88% vs 86-87%) 3