A 72-year-old post-surgical patient develops Clostridioides difficile colitis after cephalosporin therapy. The first-line treatment is fidaxomicin rather than oral vancomycin because fidaxomicin:

• A Has superior tissue penetration reaching the colonic mucosa where C. difficile vegetative forms reside
• B Kills C. difficile spores directly, preventing environmental persistence and reinfection
• C Blocks toxin A and toxin B production more effectively than vancomycin at equivalent concentrations
• D Inhibits C. difficile RNA polymerase with minimal systemic absorption and lower recurrence rates due to preservation of Bacteroides spp. ✓

Explanation

Fidaxomicin inhibits bacterial RNA polymerase at a site distinct from rifampicin, primarily targeting C. difficile. It has extremely low systemic absorption (<1%) maintaining high colonic concentrations. Crucially, it has minimal activity against Bacteroides fragilis group — key commensal bacteria that colonize resistance against C. difficile. By preserving this protective microbiome, fidaxomicin has significantly lower clinical recurrence rates (~13%) compared to oral vancomycin (~25%). It does not kill spores and does not neutralize toxins.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.