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

Treatment of Clostridioides difficile Infection

For C. difficile infection, oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) are the recommended first-line treatments, with treatment choice based on disease severity and risk of recurrence. 1

Initial Treatment Based on Disease Severity

Non-Severe CDI

• First-line options:
  • Oral vancomycin: 125 mg four times daily for 10 days 2, 1
  • Fidaxomicin: 200 mg twice daily for 10 days 1, 3
  • Note: Metronidazole (500 mg three times daily for 10 days) is no longer recommended as first-line therapy when vancomycin or fidaxomicin are available 4, 5

Severe CDI

• First-line treatment:
  • Oral vancomycin: 125 mg four times daily for 10 days 2, 1
  • Consider higher doses (up to 500 mg four times daily) in severe cases 1

Fulminant CDI (with hypotension, shock, ileus, or megacolon)

• Intravenous metronidazole: 500 mg three times daily 2
• PLUS one of the following:
  • Oral vancomycin: 500 mg four times daily (if oral intake possible) 2
  • Intracolonic vancomycin: 500 mg in 100 mL normal saline every 4-12 hours (if ileus present) 2
  • Vancomycin via nasogastric tube: 500 mg four times daily 2

When Oral Therapy Is Not Possible

• Intravenous metronidazole: 500 mg three times daily for 10 days 2
• Consider adding intracolonic vancomycin: 500 mg in 100 mL normal saline every 4-12 hours 2

Treatment of Recurrent CDI

First Recurrence

• Preferred treatment:
  • Fidaxomicin: 200 mg twice daily for 10 days 1, 4
  • Alternative: Oral vancomycin: 125 mg four times daily for 10 days 2, 1

Second or Subsequent Recurrences

• Options (in order of preference):
  1. Fecal Microbiota Transplantation (FMT) after vancomycin lead-in 1, 4
  2. Vancomycin taper/pulse 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 2, 1
  3. Fidaxomicin extended-pulsed regimen: 200 mg twice daily for 5 days, then 200 mg every other day for days 6-25 1
  4. Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy with standard antibiotics for patients with high risk of recurrence 1, 4

Special Considerations

Pediatric Patients

• For non-severe CDI: Either metronidazole or vancomycin can be used 2
• For severe CDI: Oral vancomycin is recommended 2
• Dosing for children:
  • Metronidazole: 10 mg/kg/dose (max 500 mg) three times daily 2
  • Vancomycin: 10 mg/kg/dose (max 125 mg) four times daily 2

Elderly Patients

• Higher risk of morbidity, mortality, and recurrence 1
• Oral vancomycin is preferred over metronidazole as first-line treatment 1
• Consider early use of fidaxomicin to reduce recurrence risk 1, 4

Surgical Management

• Colectomy should be performed in cases of:
  • Perforation of the colon 2
  • Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy 2
  • Toxic megacolon or severe ileus 2
• Surgery should be performed before serum lactate exceeds 5.0 mmol/L 2

Additional Management Strategies

Discontinuation of Inciting Antibiotics

• Stop unnecessary antibiotics as soon as possible 2, 1
• For mild CDI clearly induced by antibiotics with stool frequency <4 times daily and no signs of severe colitis, consider discontinuing the inducing antibiotic and observing clinical response 2

Infection Control

• Hand hygiene with soap and water (preferred during outbreaks) 1
• Environmental cleaning with sporicidal agents 1
• Isolation of patients with suspected CDI 2

Avoid

• Antiperistaltic agents and opiates should be avoided, especially in acute settings 2
• Unnecessary antibiotics following CDI treatment 1
• Prophylactic antibiotics for CDI prevention 2

Follow-up

• Monitor for symptom resolution 1
• Follow patients for at least 8 weeks after treatment to assess for recurrence 1

The treatment landscape for C. difficile infection has evolved significantly, with metronidazole no longer recommended as first-line therapy and increased emphasis on fidaxomicin and fecal microbiota transplantation for recurrent cases. Treatment decisions should consider disease severity, risk factors for recurrence, and patient characteristics to optimize outcomes and reduce mortality.