Treatment of Clostridioides difficile Infection

First-Line Treatment for Initial Episode

• The Infectious Diseases Society of America recommends oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days as first-line therapy for both non-severe and severe initial CDI episodes 1, 2
• Non-severe CDI is defined as a white blood cell count ≤15,000 cells/μL and serum creatinine <1.5 mg/dL, while severe CDI is defined as a white blood cell count >15,000 cells/μL or serum creatinine ≥1.5 mg/dL 1, 2

Disease Severity Classification

• Fulminant CDI is characterized by hypotension or shock, ileus, or megacolon 1

Treatment Selection

• The preferred regimen for initial episode, regardless of severity, is vancomycin 125 mg orally four times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• For non-severe CDI, metronidazole 500 mg three times daily orally for 10-14 days is an alternative option only if vancomycin and fidaxomicin are unavailable 1

Treatment for First Recurrence

• The preferred therapy for first CDI recurrence is fidaxomicin 200 mg twice daily for 10 days 1, 2
• Alternative options include vancomycin in a tapered and pulsed regimen or standard vancomycin 125 mg four times daily for 10 days 1, 2

Treatment for Second or Subsequent Recurrence

• For multiple recurrences, treatment options include vancomycin in a tapered/pulsed regimen, fidaxomicin extended regimen, vancomycin followed by rifaximin, or fecal microbiota transplantation after at least 2 recurrences 1, 2

Fulminant CDI Management

• For fulminant CDI, high-dose vancomycin 500 mg four times daily orally or by nasogastric tube plus intravenous metronidazole 500 mg every 8 hours is recommended 1, 2
• If ileus is present, vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours should be added 1, 3

NPO Patients

• For patients unable to take oral medications, IV metronidazole 500 mg every 8 hours plus vancomycin retention enema 500 mg in 100 mL normal saline four times daily is recommended 3, 4

Critical Management Principles

• Discontinuing inciting antibiotics as soon as medically feasible is essential 1, 2
• Standard treatment duration is 10 days, which may be extended to 14 days if there is a delayed response 1, 2
• Antiperistaltic agents and opiates should be avoided 3
• A "test of cure" should not be performed after treatment completion 2, 4