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

Treatment of Clostridioides difficile Infection

Oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for initial C. difficile infection regardless of disease severity. 1, 2

Initial Episode Treatment

Non-Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days is recommended as first-line therapy for all initial episodes, including non-severe cases 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with lower recurrence rates 1, 2, 3
• Metronidazole 500 mg orally three times daily for 10 days may be used only for non-severe initial episodes when vancomycin or fidaxomicin are unavailable, but this is no longer preferred due to increasing treatment failures 1, 4, 5

Severe Disease

Severe CDI is defined by one or more of the following: WBC >15 × 10⁹/L, serum albumin <30 g/L, or serum creatinine ≥1.5 times baseline 1, 2, 4

• Vancomycin 125 mg orally four times daily for 10 days is the treatment of choice 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative 1, 2
• Metronidazole should NOT be used for severe disease 2

Fulminant Disease

Fulminant CDI presents with hypotension, shock, ileus, toxic megacolon, or peritonitis 2

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 1, 2
• When oral administration is not possible, use intravenous metronidazole 500 mg three times daily combined with vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema 6, 1
• Early surgical consultation is essential for patients with systemic toxicity, perforation, or toxic megacolon 2, 4

Recurrent C. difficile Infection

First Recurrence

• Vancomycin 125 mg four times daily for 10 days is recommended, especially if metronidazole was used for the initial episode 1, 2
• Fidaxomicin 200 mg twice daily for 10 days is preferred when vancomycin was used initially, due to lower recurrence rates 6, 1, 2
• Avoid metronidazole for recurrent episodes due to lower sustained response rates and risk of cumulative neurotoxicity 1, 2

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen: 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks 6, 1
• Fecal microbiota transplantation (FMT) should be considered for multiple recurrences after appropriate antibiotic therapy 1, 2
• Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may prevent recurrences in high-risk patients 2

Pediatric Treatment (≥6 months of age)

Non-Severe First Episode or First Recurrence

• Metronidazole 7.5 mg/kg/dose (max 500 mg) orally four times daily for 10 days OR vancomycin 10 mg/kg/dose (max 125 mg) orally four times daily for 10 days 1

Severe or Fulminant Infection

• Vancomycin 10 mg/kg/dose (max 500 mg for fulminant) orally four times daily 1

Multiple Recurrences

• Vancomycin extended regimen or consideration of FMT 1

Critical Management Principles

Antibiotic Stewardship

• Discontinue the inciting antibiotic as soon as clinically possible to reduce recurrence risk 1, 2, 4

Infection Control

• Hand hygiene must be performed with soap and water, NOT alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 2
• Implement contact precautions and environmental cleaning with sporicidal agents 2

Medications to Avoid

• Do not use antiperistaltic agents or opiates, as they may worsen colitis 4
• Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

Common Pitfalls

• Do not delay treatment for severe CDI while awaiting diagnostic confirmation 2
• Do not use metronidazole for severe or recurrent infections - it has inferior efficacy and potential toxicity 2
• Do not stop treatment early even if symptoms improve - complete the full 10-day course to prevent recurrence and resistance 1, 5
• Fidaxomicin may increase cost but reduces recurrence rates compared to vancomycin, particularly valuable in patients at high risk for recurrence 6, 1