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

Treatment of Clostridioides difficile Infection

First-Line Treatment for Initial Episodes

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

Treatment Options by Severity

Non-Severe CDI:

• Vancomycin 125 mg orally four times daily for 10 days is preferred for all cases 1, 2
• Metronidazole 500 mg orally three times daily for 10 days may be used as an alternative for non-severe cases only, though it is inferior to vancomycin 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with lower recurrence rates 1, 2, 4

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

• Vancomycin 125 mg orally four times daily for 10 days is the treatment of choice 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with demonstrated lower recurrence rates 1, 2

Fulminant CDI (with hypotension, shock, ileus, toxic megacolon, or peritonitis):

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 1, 2
• When oral administration is not possible, use vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema, combined with IV metronidazole 1
• Obtain early surgical consultation for patients with systemic toxicity, perforation, or toxic megacolon 1, 2, 3

Treatment of Recurrent CDI

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 lower recurrence rates 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 1
• Fecal microbiota transplantation (FMT) is recommended for multiple recurrences that have failed appropriate antibiotic treatments 1, 2
• Bezlotoxumab (monoclonal antibody against C. diff toxin B) may prevent recurrences in high-risk patients 2

Pediatric Treatment (≥6 months of age)

Non-Severe or First Recurrence:

• Metronidazole 7.5 mg/kg/dose (max 500 mg) 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 4

Severe or Fulminant:

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

Multiple Recurrences:

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

Critical Management Principles

Essential Adjunctive Measures:

• Discontinue the inciting antibiotic as soon as clinically possible to reduce recurrence risk 1, 2
• Avoid antiperistaltic agents and opiates 3
• Hand hygiene must be performed with soap and water, NOT alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 2

Monitoring:

• Assess clinical response within 3 days of treatment initiation 3
• Treatment failure is defined as absence of improvement after 3-5 days 3

Important Caveats

Metronidazole Limitations:

• Should be limited to initial episodes of non-severe CDI only 1
• Never use for severe or recurrent CDI due to lower efficacy 2
• Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2

Fidaxomicin Considerations:

• Higher cost but reduces recurrence rates compared to vancomycin 1
• Particularly valuable in patients at high risk for recurrence 1
• May reduce risk of vancomycin-resistant bacteria acquisition compared to vancomycin 1

Surgical Intervention:

• Subtotal colectomy with end ileostomy is the established procedure for systemic toxicity, perforation, or toxic megacolon 1
• Loop ileostomy with colonic lavage is emerging as a colon-salvage alternative 1
• Surgery should be performed before colitis becomes very severe, ideally before significant clinical deterioration 3