Which antibiotic is NOT considered first-line for mild-to-moderate C. difficile infection?

• A. Metronidazole
• B. Fidaxomicin
• C. Oral vancomycin
• D. Daptomycin

Answer: (A)

Metronidazole is no longer considered a first-line option for mild-to-moderate C. difficile infection. Current guidelines favor oral vancomycin or fidaxomicin because they achieve high, sustained concentrations in the colon where the infection sits, leading to higher cure rates and lower recurrence. Metronidazole, on the other hand, is more readily absorbed from the gut, resulting in lower colonic drug levels and less reliable eradication of C. difficile, which contributes to poorer outcomes and more relapses. Daptomycin isn’t used for C. difficile at all, so it isn’t chosen as a first-line therapy. Therefore, metronidazole is the correct choice as not being first-line.