What is the treatment for Clostridioides difficile (Cdiff) infection?

Treatment of Clostridioides difficile Infection (CDI)

For Clostridioides difficile infection, either vancomycin or fidaxomicin is recommended over metronidazole as first-line therapy, with treatment selection based on disease severity. 1

Disease Severity Classification

• CDI is classified as non-severe or severe based on specific clinical and laboratory parameters 1
• Severe CDI is characterized by:
  • Leukocytosis (WBC >15 × 10^9/L)
  • Serum albumin <30 g/L
  • Rise in serum creatinine (≥1.5 times baseline)
  • Fever >38.5°C
  • Hemodynamic instability
  • Signs of peritonitis or ileus
  • Pseudomembranous colitis on endoscopy 1, 2

Initial Treatment Algorithm

For Non-Severe CDI:

• 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 (if access to vancomycin or fidaxomicin is limited): Metronidazole 500 mg orally three times daily for 10 days 1, 2
• For mild CDI clearly induced by antibiotics, consider stopping the inciting antibiotic and observing closely, but be prepared to start therapy immediately if clinical deterioration occurs 1

For Severe CDI:

• First-line: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2

When Oral Therapy Is Not Possible:

• Non-severe: Metronidazole 500 mg intravenously three times daily for 10 days 1
• Severe: Metronidazole 500 mg intravenously three times daily for 10 days PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 1

Treatment of Recurrent CDI

• First recurrence: Treat as an initial episode based on severity 1, 2
• Second and subsequent recurrences (if oral therapy is possible):
  • Vancomycin 125 mg orally four times daily for at least 10 days 1, 2
  • Consider a vancomycin taper/pulse strategy after the initial course (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 1, 2
• For multiple recurrences: Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment 1, 2, 3

Surgical Management

• Surgical consultation should be obtained for patients with severe CDI who develop systemic toxicity 1, 2
• Indications for surgery include:
  • Perforation of the colon
  • Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy
  • Toxic megacolon
  • Severe ileus 1, 2
• Surgery should be performed before colitis becomes very severe (before serum lactate exceeds 5.0 mmol/L) 1

Important Considerations and Pitfalls

• Discontinue the inciting antibiotic if possible, as continued use significantly increases the risk of CDI recurrence 1, 2
• Avoid antiperistaltic agents and opiates, especially in the acute setting, as they may mask symptoms and potentially worsen disease 1, 2
• Hand hygiene should be performed with soap and water, not alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 2
• Fidaxomicin has been shown to have lower recurrence rates compared to vancomycin, particularly in patients at high risk for recurrence 1, 2, 4
• Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may be considered as adjunctive therapy to prevent recurrences, especially in high-risk patients 1, 2
• Metronidazole should be avoided for repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1

Special Populations

• For immunocompromised patients or those with severe comorbidities, consider using vancomycin or fidaxomicin as first-line therapy regardless of disease severity 1, 2
• For pregnant patients, vancomycin is preferred over metronidazole due to potential teratogenic effects of metronidazole 2
• For pediatric patients 6 months of age and older, fidaxomicin is FDA-approved for treatment of C. difficile-associated diarrhea 5