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

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of C. difficile infection, oral vancomycin or fidaxomicin are now the first-line treatments, with metronidazole no longer recommended as first-line therapy for adults. 1

Initial Treatment Based on Severity

Non-severe CDI

• First-line:
  • Vancomycin 125 mg orally four times daily for 10 days 1
  • OR Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Alternative (only if above options unavailable):
  • Metronidazole 500 mg orally three times daily for 10 days 3, 1
  • Note: Metronidazole has decreased efficacy and higher risk of neurotoxicity 1

Severe CDI

• Definition: WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 1
• Treatment:
  • Vancomycin 125 mg orally four times daily for 10 days 3, 1
  • OR Fidaxomicin 200 mg orally twice daily for 10 days 1, 2

Fulminant CDI

• Definition: Hypotension, shock, ileus, or megacolon 1
• Treatment:
  • Vancomycin 500 mg orally four times daily 1
  • PLUS IV metronidazole 500 mg every 8 hours 1
  • If oral therapy impossible: IV 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 3

Treatment of Recurrent CDI

First Recurrence

• First-line:
  • Vancomycin 125 mg orally four times daily for 10 days 3, 1
  • OR Fidaxomicin 200 mg orally twice daily for 10 days (especially if vancomycin was used for initial episode) 1, 2

Second or Subsequent Recurrences

• First-line:
  • Vancomycin using a tapered and pulsed regimen 3, 1:
    • 125 mg four times daily for 10-14 days
    • Then 125 mg twice daily for 7 days
    • Then 125 mg once daily for 7 days
    • Then 125 mg every 2-3 days for 2-8 weeks
• Alternative:
  • Fecal microbiota transplantation (FMT) for multiple recurrences after appropriate antibiotic therapy for at least three episodes 1, 4
  • FMT has shown cure rates of 70-90% in severe and fulminant CDI 5

Pediatric Treatment (6 Months to Less than 18 Years)

• Vancomycin 40 mg/kg/day in 3-4 divided doses (max 2g/day) 1
• OR Fidaxomicin (if ≥6 months old) 2:
  • For weight ≥12.5 kg: 200 mg tablet twice daily for 10 days
  • For weight <12.5 kg: Weight-based dosing of oral suspension

Surgical Management

• Colectomy should be considered in:
  • Perforation of the colon
  • Systemic inflammation not responding to antibiotic therapy
  • Toxic megacolon or severe ileus
  • Surgery preferably before serum lactate exceeds 5.0 mmol/L 3, 1

Important Adjunctive Measures

1. Discontinue the inciting antibiotic whenever possible 1
2. Avoid antiperistaltic agents and opiates 3
3. Provide supportive care including fluid and electrolyte replacement 1
4. Practice proper hand hygiene (soap and water preferred over alcohol-based sanitizers) 1

Treatment Pitfalls to Avoid

1. Do not use metronidazole for recurrent CDI due to lower response rates and risk of cumulative neurotoxicity 1, 6
2. Do not treat mild CDI with antibiotics if it can be managed by stopping the inciting antibiotic (observe closely for deterioration) 3
3. Do not use antiperistaltic agents as they can worsen outcomes 3
4. Do not delay surgical consultation in fulminant cases not responding to medical therapy 1
5. Do not test for cure after treatment if symptoms resolve 7

Risk Factors for Recurrence

• Advanced age
• Continued use of antibiotics during or after CDI treatment
• Defective immune response against C. difficile toxins
• Severe underlying disease
• Use of proton pump inhibitors
• Previous CDI episodes 1

The treatment of CDI has evolved significantly, with vancomycin and fidaxomicin now being the cornerstones of therapy 6. The microbiome-sparing properties of fidaxomicin may reduce recurrence risk 8, making it an increasingly preferred option despite higher cost. For patients with multiple recurrences, FMT has emerged as a highly effective treatment strategy 4, 5.