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

Treatment of Clostridioides difficile Infection

For initial C. difficile 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 effective alternative that reduces recurrence rates. 1, 2

Initial Episode Treatment Strategy

Non-Severe CDI (First Episode)

• 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, 3
• Metronidazole 500 mg orally three times daily for 10 days may be used for non-severe cases only, but is increasingly disfavored due to treatment failures and should be limited to initial mild-moderate episodes 1, 4, 5

Non-severe disease is defined by stool frequency < 4 times daily, WBC < 15 × 10⁹/L, and normal serum albumin and creatinine 4, 2

Severe CDI (First Episode)

• 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, 3
• Metronidazole should NOT be used for severe disease 1

Severe disease is characterized by: WBC > 15 × 10⁹/L, serum albumin < 30 g/L, rise in serum creatinine ≥1.5 times baseline, temperature > 38.5°C, or hemodynamic instability 4, 2

Fulminant CDI

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 1
• When oral administration is not possible: intravenous metronidazole 500 mg three times daily PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily via nasogastric tube 6, 1
• Early surgical consultation is mandatory for patients with systemic toxicity, perforation, toxic megacolon, or severe ileus 1, 2
• Surgery should be performed before colitis becomes very severe, ideally before serum lactate exceeds 5.0 mmol/L 6

Recurrent CDI Treatment

First Recurrence

• Vancomycin 125 mg four times daily for 10 days is recommended, especially if metronidazole was used initially 1, 4
• 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, 3
• Avoid metronidazole for recurrent episodes due to lower sustained response rates and risk of cumulative neurotoxicity 1, 4

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, 4
• Fecal microbiota transplantation (FMT) should be strongly considered for multiple recurrences 1, 2
• Fidaxomicin 200 mg twice daily for 10 days remains an option 1

Pediatric Dosing (≥6 months to <18 years)

Tablets (for children ≥12.5 kg who can swallow tablets)

• 200 mg orally twice daily for 10 days 3

Oral Suspension (weight-based dosing)

• 4 kg to <7 kg: 80 mg (2 mL) twice daily 3
• 7 kg to <9 kg: 120 mg (3 mL) twice daily 3
• 9 kg to <12.5 kg: 160 mg (4 mL) twice daily 3
• ≥12.5 kg: 200 mg (5 mL) twice daily 3

For severe or fulminant infection in children: vancomycin 10 mg/kg/dose (max 500 mg) every 8 hours for 10 days, with or without IV metronidazole 1

Critical Adjunctive Measures

• Discontinue the inciting antibiotic immediately if clinically possible 1, 4, 2
• Avoid antiperistaltic agents and opiates, as they may worsen disease 6, 4
• Hand hygiene must be performed with soap and water, NOT alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 4
• Monitor for clinical response within 3 days; treatment failure is defined as absence of improvement after 3-5 days 4, 2
• No follow-up stool testing is needed if symptoms resolve 4

Important Caveats

Metronidazole is no longer recommended as first-line therapy due to increasing treatment failures and concerns about resistance, and should be avoided for severe disease and all recurrent episodes 1, 5, 7. The shift away from metronidazole represents a major change from older guidelines 6.

Fidaxomicin has consistently demonstrated lower recurrence rates compared to vancomycin across multiple studies, making it particularly valuable for patients at high risk for recurrence, though cost may be a consideration 1, 7. The FDA has approved fidaxomicin for patients ≥6 months of age 3.

Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may be administered intravenously to prevent recurrences in high-risk patients, though this is an adjunctive therapy and not a replacement for antibiotics 4, 7.