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

Treatment of Clostridioides difficile Infection

For initial episodes of C. difficile infection (CDI), oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) is strongly recommended over metronidazole as first-line therapy. 1, 2

Classification and Treatment Algorithm

1. Initial Episode Treatment

Based on disease severity:

• Non-severe CDI (WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL):

  • First-line: Vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days 1, 2
  • Alternative (only if access to vancomycin/fidaxomicin is limited): Metronidazole 500 mg orally three times daily for 10 days 1
  • Note: Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

• Severe CDI (WBC ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL OR serum albumin <30 g/L):

  • Vancomycin 125 mg orally four times daily for 10 days OR fidaxomicin 200 mg orally twice daily for 10 days 2

• Fulminant/Complicated CDI (hypotension, shock, ileus, or toxic megacolon):

  • Vancomycin 500 mg orally four times daily AND metronidazole 500 mg IV every 8 hours 1, 2
  • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline as retention enema every 6 hours 1, 2
  • Consider early surgical consultation for patients with rising WBC count (≥25,000) or rising lactate level (≥5 mmol/L) 1

2. Recurrent CDI Treatment

• First Recurrence:

  • If metronidazole was used for initial episode: Vancomycin 125 mg orally four times daily for 10 days 1, 2
  • If standard vancomycin was used for initial episode: Fidaxomicin 200 mg twice daily for 10 days OR vancomycin in a tapered and pulsed regimen 1, 2

• Multiple Recurrences (options include):

  • Vancomycin in a tapered and pulsed regimen 1, 2
  • Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1, 2
  • Fidaxomicin 200 mg twice daily for 10 days 1, 2
  • Fecal microbiota transplantation (FMT) after appropriate antibiotic treatments for at least 2 recurrences 1, 2

Special Considerations

Pediatric Patients

• For children 6 months and older:
  • Fidaxomicin is FDA-approved for children ≥6 months 3
  • Weight-based dosing for oral suspension is available for children who cannot swallow tablets 3
  • For severe CDI in children: Vancomycin with or without IV metronidazole 2

Supportive Measures

• Discontinue the inciting antibiotic as soon as possible to improve clinical response and reduce recurrence risk 1, 2
• Avoid antimotility agents and opiates in the acute setting as they may worsen symptoms 2
• Consider discontinuing proton pump inhibitors if not essential 2
• Provide supportive care including IV fluids and electrolyte replacement 2

Prevention and Infection Control

• Implement proper hand hygiene with soap and water (preferred over alcohol-based products during outbreaks) 2, 4
• Use contact precautions for infected patients 2
• Thorough environmental cleaning and disinfection 2
• Antibiotic stewardship to reduce unnecessary antibiotic use 2, 4

Emerging Therapies

• Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, can be considered to reduce CDI recurrence, particularly in high-risk patients (immunocompromised, severe CDI, or infection with the 027 epidemic strain) 2

Common Pitfalls to Avoid

• Do not repeat C. difficile testing within 7 days during the same episode of diarrhea as it rarely changes management and may lead to false positive results 2
• Do not use metronidazole as first-line therapy for adults with CDI, as recent studies show it is inferior to vancomycin for clinical cure 1, 4
• Do not test asymptomatic patients or those taking laxatives 2, 4
• Do not use probiotics for prevention of CDI as they are not recommended by the Infectious Diseases Society of America 4
• Do not delay empiric treatment in cases of fulminant CDI or when substantial laboratory delay is expected 1

The treatment landscape for CDI has evolved significantly, with vancomycin and fidaxomicin now preferred over metronidazole for initial episodes based on superior efficacy demonstrated in randomized controlled trials 1, 4.