Treatment of Clostridioides difficile Infection (C. diff)

Initial Treatment Based on Disease Severity

For non-severe C. diff infection, the Infectious Diseases Society of America recommends metronidazole 500 mg orally three times daily for 10 days, or vancomycin 125 mg orally four times daily for 10 days as alternative therapy 1, 3
For severe C. diff infection, the Infectious Diseases Society of America recommends vancomycin 125 mg orally four times daily for 10 days, with fidaxomicin 200 mg orally twice daily for 10 days as an alternative 1, 5
The American College of Gastroenterology suggests that fidaxomicin has fewer recurrences compared to vancomycin 5

The Infectious Diseases Society of America defines severe C. diff infection as marked by leukocytosis (WBC >15 × 10^9/L), serum albumin <30 g/L, or rise in serum creatinine (≥133 μM or ≥1.5 times premorbid level) 7
Advanced age and significant comorbidities may also be considered markers of severe disease 1, 4

For first recurrence, the Infectious Diseases Society of America recommends treating as an initial episode based on severity, with vancomycin or fidaxomicin as first-line therapy 4, 6
For second and subsequent recurrences, the Infectious Diseases Society of America suggests vancomycin 125 mg orally four times daily for at least 10 days, with consideration of a vancomycin taper/pulse strategy after the initial course 8, 4

The Infectious Diseases Society of America recommends discontinuing the inciting antibiotic if possible, as continued use significantly increases risk of recurrence 2
Bezlotoxumab (monoclonal antibody against C. diff toxin B) may prevent recurrences, particularly in high-risk patients 2

The World Society of Emergency Surgery recommends surgical consultation for patients with severe CDI who develop systemic toxicity, with indications for surgery including perforation of the colon, systemic inflammation with deteriorating clinical condition, toxic megacolon, or severe ileus 2, 8, 3
Total colectomy has been the traditional surgical approach, but diverting loop ileostomy with colonic lavage is emerging as a viable alternative with potentially lower mortality 2

The Centers for Disease Control and Prevention recommend hand hygiene with soap and water (not alcohol-based sanitizers) to prevent transmission, as alcohol does not kill C. diff spores 2
The Infectious Diseases Society of America advises avoiding antiperistaltic agents and opiates as they may mask symptoms and worsen disease 3