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

Treatment of Clostridioides difficile Infection

For initial C. diff infection, oral vancomycin 125 mg four times daily for 10 days is the first-line treatment regardless of disease severity, with fidaxomicin 200 mg twice daily for 10 days as an excellent alternative that reduces recurrence rates. 1, 2

Initial Episode Treatment by Severity

Non-Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days is recommended as first-line therapy 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 can be used for non-severe cases, but is now considered inferior due to increasing treatment failures and should be limited to situations where vancomycin or fidaxomicin are unavailable 1, 4, 5

Severe Disease

Severe CDI is defined by: leukocytosis (WBC >15 × 10⁹/L), serum albumin <30 g/L, or rise in serum creatinine (≥1.5 times baseline) 1, 2

• Vancomycin 125 mg orally four times daily for 10 days remains the treatment of choice 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with demonstrated lower recurrence rates 1, 2

Fulminant Disease

Fulminant CDI presents with hypotension, shock, ileus, toxic megacolon, or peritonitis 1

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 1
• When oral administration is not possible: vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema, combined with IV metronidazole 500 mg three times daily 1
• Early surgical consultation is mandatory for patients with systemic toxicity 1, 2
• Surgical options include subtotal colectomy with end ileostomy, though loop ileostomy with colonic lavage is emerging as a colon-salvage alternative 1

Recurrent C. diff Infection

First Recurrence

• Vancomycin 125 mg four times daily for 10 days, especially if metronidazole was used initially 1, 2
• Fidaxomicin 200 mg twice daily for 10 days is preferred when vancomycin was used for the first episode, due to significantly lower recurrence rates 1, 3
• Avoid metronidazole for recurrent episodes due to lower sustained response rates 1

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 1, 2
• Fecal microbiota transplantation (FMT) should be strongly considered for multiple recurrences 1, 4
• Bezlotoxumab (monoclonal antibody against C. diff toxin B) may prevent recurrences, particularly in high-risk patients 2, 4

Pediatric Dosing (≥6 months old)

Non-Severe or First Recurrence

• Metronidazole 7.5 mg/kg/dose (max 500 mg) four times daily for 10 days OR vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 1
• For children ≥12.5 kg who can swallow tablets: fidaxomicin 200 mg twice daily for 10 days 3
• For children <12.5 kg: fidaxomicin oral suspension dosed by weight (see FDA label for specific dosing) 3

Severe or Fulminant Infection

• Vancomycin 10 mg/kg/dose (max 500 mg) every 8 hours for 10 days, with or without IV metronidazole 1

Multiple Recurrences in Children

• Vancomycin extended regimen (same tapering schedule as adults, weight-adjusted) 1
• FMT should be considered 1

Critical Adjunctive Measures

Antibiotic Stewardship

• Discontinue the inciting antibiotic as soon as clinically possible—this is one of the most important interventions to reduce recurrence risk 1, 2, 6

Infection Control

• Hand hygiene must be performed with soap and water, NOT alcohol-based sanitizers, as alcohol does not kill C. diff spores 1, 2, 6

Medications to Avoid

• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 2, 6
• Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

Important Clinical Pitfalls

• Metronidazole is no longer recommended as first-line therapy due to increasing treatment failures and inferior outcomes compared to vancomycin and fidaxomicin 4, 5
• Fidaxomicin has higher cost but provides lower recurrence rates, making it particularly valuable in patients at high risk for recurrence 1
• Vancomycin may increase the risk of vancomycin-resistant bacteria acquisition compared to fidaxomicin 1
• Monitor for clinical response (decreased stool frequency, improved consistency) within 3 days of treatment 6
• No follow-up stool testing is needed if symptoms resolve 6
• Watch for signs of treatment failure (absence of improvement after 3-5 days) 6