What is the recommended first-line therapy for mild-to-moderate C. difficile infection in adults?

• A. Oral vancomycin or fidaxomicin
• B. Metronidazole
• C. Amoxicillin-clavulanate
• D. Ciprofloxacin

Answer: (A)

For a first episode of mild-to-moderate C. difficile infection, you want an antibiotic that stays in the gut where the infection is and has strong, sustained effectiveness with minimal disruption to the rest of the gut flora. Oral vancomycin and fidaxomicin do exactly that. They act locally in the colon, reliably clear the infection, and fidaxomicin, in particular, is associated with lower recurrence rates after treatment. Metronidazole used to be considered a first-line option, but it is less effective for initial episodes and carries systemic side effects, making it a suboptimal choice now. The other antibiotics listed—amoxicillin-clavulanate and ciprofloxacin—don’t treat C. difficile and can worsen the situation by further disturbing the gut microbiota. So the best first-line therapy is oral vancomycin or fidaxomicin.