Treatment of Clostridioides difficile Infection
For initial C. difficile infection (CDI), fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment due to superior sustained clinical response rates and lower recurrence rates compared to other options. 1
Treatment Algorithm Based on Disease Severity
Non-severe Initial CDI
- First choice: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
- Alternative: Vancomycin 125 mg orally four times daily for 10 days 3, 1
- Limited use: Metronidazole 500 mg orally three times daily for 10 days (only for patients ≤65 years with limited access to first-line agents) 1
Severe CDI
Severe CDI is characterized by hypotension, shock, ileus, megacolon, or markers such as:
- WBC >15,000 cells/mm³
- Serum creatinine ≥1.5 mg/dL
- Age >60 years
- Hypoalbuminemia
Treatment:
- First choice: Vancomycin 125 mg orally four times daily for 10 days 3, 1
- Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 3, 1
Severe-Complicated/Fulminant CDI
- Vancomycin 500 mg orally four times daily 1
- PLUS intravenous metronidazole 500 mg every 8 hours 1
- If ileus present: Add rectal instillation of vancomycin 500 mg in 100 mL normal saline every 4-12 hours 1
Treatment of Recurrent CDI
First Recurrence
- Preferred: Fidaxomicin 200 mg twice daily for 10 days 1, 4
- Reduces second recurrence to 19.7% vs. 35.5% with vancomycin 4
- Alternative regimen: Fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1
Multiple Recurrences (≥2)
- Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment 1, 5
- Success rates of 70-90% in preventing further recurrences
- Adjunctive therapy: Bezlotoxumab 10 mg/kg IV once during antibiotic administration, particularly for immunocompromised patients 1
Special Populations
Pediatric Patients (6 months to <18 years)
- Fidaxomicin is FDA-approved for children 6 months and older 2
- Weight-based dosing for oral suspension:
- 4 kg to <7 kg: 80 mg (2 mL) twice daily
- 7 kg to <9 kg: 120 mg (3 mL) twice daily
- 9 kg to <12.5 kg: 160 mg (4 mL) twice daily
- ≥12.5 kg: 200 mg (5 mL) twice daily
- Children able to swallow tablets and weighing ≥12.5 kg: 200 mg tablet twice daily 2
- Alternative: Metronidazole 7.5 mg/kg/dose (maximum 500 mg) three or four times daily for 10 days 1
Infection Control Measures
- Strict hand hygiene with soap and water (not alcohol-based sanitizers) 1
- Contact precautions with isolation and personal protective equipment 1
- Thorough environmental cleaning with sporicidal agents 1
- Discontinue the inciting antibiotic as soon as possible 1
Important Clinical Considerations
- Expect clinical improvement within 2-3 days; reassess if no improvement within 48-72 hours 1
- Monitor for treatment response and consider alternative therapy if symptoms persist 1
- For patients on metronidazole, monitor for peripheral neuropathy with prolonged therapy 1
- Monitor renal function in patients >65 years during and after vancomycin treatment 1
Key Paradigm Shifts in CDI Treatment
- Metronidazole is no longer recommended as first-line therapy for adults 1, 5, 6
- Fidaxomicin has emerged as preferred therapy due to microbiome-sparing properties and lower recurrence rates 1, 7
- FMT has become established as effective therapy for multiple recurrent CDI 1, 5, 8
The treatment landscape for CDI continues to evolve, with increasing emphasis on preventing recurrence through microbiome-sparing approaches and targeted therapies rather than broad-spectrum antibiotics that may perpetuate the cycle of dysbiosis and recurrence.