What is the treatment for Clostridioides difficile (C-diff) infection?

Treatment of Clostridioides difficile (C-diff) Infection

Fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment for C. difficile infection (CDI) due to superior sustained clinical response rates and lower recurrence rates. 1

Treatment Algorithm Based on Disease Severity

Initial CDI Episode

1. First-line treatment options:

   • Fidaxomicin: 200 mg orally twice daily for 10 days (preferred) 1
   • Vancomycin: 125 mg orally four times daily for 10 days (alternative) 1, 2
   • Metronidazole: 500 mg orally three times daily for 10-14 days (limited use - only for mild-moderate cases in patients ≤65 years when other options unavailable) 1

2. For severe CDI (hypotension, shock, ileus, or megacolon):

   • Vancomycin: 500 mg orally four times daily 3, 1
   • Add rectal instillation of vancomycin if ileus is present 1
   • Add intravenous metronidazole: 500 mg every 8 hours 1

Recurrent CDI

1. First recurrence:

   • Fidaxomicin: 200 mg twice daily for 10 days OR
   • Fidaxomicin: 200 mg twice daily for 5 days followed by once every other day for 20 days 1

2. Second or subsequent recurrence:

   • Consider Fecal Microbiota Transplantation (FMT) after appropriate antibiotic treatments (70-90% success rates) 3, 1
   • Bezlotoxumab: 10 mg/kg IV once during antibiotic administration may be considered as adjunctive therapy, particularly for immunocompromised patients 3, 1

Important Considerations

Discontinue Inciting Antibiotics

• If possible, discontinue the antibiotic that triggered the CDI to reduce risk of recurrence 3, 1
• If continued antibiotic therapy is required, use agents less frequently associated with CDI (aminoglycosides, sulfonamides, macrolides, vancomycin, tetracycline/tigecycline) 3

Monitoring Treatment Response

• Improvement typically expected within 2-3 days 1
• If no improvement within 48-72 hours, reassess severity and consider alternative treatments 1

Special Populations

Pediatric Patients

• Metronidazole: 7.5 mg/kg/dose (maximum 500 mg) three or four times daily for 10 days 1

Elderly Patients (>65 years)

• Monitor renal function during and after vancomycin treatment due to increased risk of nephrotoxicity 1, 2
• Higher risk of adverse effects including hypokalemia, urinary tract infection, peripheral edema, and hypotension 2

Infection Control Measures

• Place patients in private rooms with en suite facilities when possible 3
• Implement strict hand hygiene with soap and water (alcohol-based sanitizers are ineffective against C. difficile spores) 3, 1
• Use contact precautions and thorough environmental cleaning 3, 1

Adverse Effects to Monitor

• Vancomycin: Nephrotoxicity (especially in patients >65 years), nausea, abdominal pain, hypokalemia 2
• Metronidazole: Gastrointestinal effects, disulfiram-like reaction with alcohol, peripheral neuropathy with prolonged therapy 1
• Fidaxomicin: Generally well-tolerated with fewer recurrences compared to other treatments 1, 4

Treatment Evolution

The treatment landscape for CDI has evolved significantly in recent years. While metronidazole was historically the first-line treatment, current guidelines now favor fidaxomicin and vancomycin due to higher cure rates and lower recurrence rates 4, 5. The emergence of hypervirulent strains like NAP1/027 has further emphasized the need for effective treatment strategies and infection control measures 6.