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

Treatment of Clostridioides difficile Infection

For initial C. difficile infection, oral vancomycin 125 mg four times daily for 10 days is the recommended first-line therapy 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 CDI (First Episode)

• Vancomycin 125 mg orally four times daily for 10 days is the preferred treatment 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 for non-severe cases, but is increasingly falling out of favor due to treatment failures 1, 4

Important caveat: While metronidazole was historically first-line, current guidelines prioritize vancomycin or fidaxomicin due to superior efficacy and the risk of metronidazole neurotoxicity with repeated courses 1, 2

Severe CDI (First Episode)

Severe disease is defined by: WBC >15 × 10^9/L, serum albumin <30 g/L, or serum creatinine ≥1.5 times baseline 2, 4

• 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 equally effective alternative 1, 2

Fulminant CDI

Fulminant disease 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, 2
• 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 1
• Early surgical consultation is mandatory for patients with systemic toxicity, perforation, or toxic megacolon 2
• Subtotal colectomy with end ileostomy is the established surgical procedure, though loop ileostomy with colonic lavage is emerging as a colon-salvage alternative 5

Recurrent CDI Treatment

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 initial episode, due to significantly lower recurrence rates 1, 2
• Avoid metronidazole for recurrent episodes due to lower sustained response rates and neurotoxicity risk 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. difficile toxin B) may be administered to prevent recurrences in high-risk patients 2, 4

Pediatric Treatment (6 Months to <18 Years)

Non-Severe or First Recurrence

• Metronidazole 7.5 mg/kg/dose (max 500 mg) three to four times daily for 10 days 5, 1
• Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 5, 1

Severe or Fulminant

• Vancomycin 10 mg/kg/dose (max 500 mg) every 8 hours for 10 days, with or without IV metronidazole 5, 1
• May be given orally or per rectum 5

Multiple Recurrences in Children

• Vancomycin extended regimen (same tapering schedule as adults, weight-adjusted) 5, 1
• FMT should be considered 5, 1

Fidaxomicin dosing for pediatrics: For children ≥6 months and ≥12.5 kg who can swallow tablets: 200 mg twice daily for 10 days; for those unable to swallow tablets, oral suspension is available with weight-based dosing 3

Critical Adjunctive Measures

• Discontinue the inciting antibiotic immediately if clinically possible, as continued use significantly increases recurrence risk 1, 2, 4
• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 2, 4
• Hand hygiene with soap and water (not alcohol-based sanitizers) is essential, as alcohol does not kill C. difficile spores 2, 4
• Discontinue chronic acid suppressive therapy when feasible 6

Key Clinical Pearls

Fidaxomicin advantages: While more expensive, fidaxomicin demonstrates lower recurrence rates compared to vancomycin and is particularly valuable in patients at high risk for recurrence 1, 7, 6. It is also microbiome-sparing, which reduces the risk of subsequent dysbiosis 7

Metronidazole limitations: Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1. Current guidelines recommend limiting metronidazole to initial episodes of mild-moderate CDI only 1

Monitoring response: Clinical improvement (decreased stool frequency, improved consistency) should be evident within 3-5 days of treatment 4. Absence of improvement warrants reassessment and consideration of treatment escalation 4

No follow-up testing needed: If symptoms resolve, no follow-up stool testing is required, as patients may remain colonized without active infection 4