A patient with a UTI due to E. coli fails ciprofloxacin therapy. Sequencing reveals a gyrA mutation at codon 83 (Ser83Leu). Which therapeutic choice is MOST appropriate?

• A Levofloxacin, as it is more potent against the same gyrA mutant
• B Ofloxacin, as it is structurally distinct from ciprofloxacin
• C Moxifloxacin, as it primarily targets topoisomerase IV rather than gyrase
• D Fosfomycin, as it acts via an entirely different mechanism targeting MurA enzyme in peptidoglycan synthesis ✓

Explanation

A gyrA Ser83Leu mutation confers high-level cross-resistance to ALL fluoroquinolones because they share the same DNA gyrase target. Levofloxacin, ofloxacin, and moxifloxacin would all be ineffective. Fosfomycin inhibits MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), the first committed step in peptidoglycan synthesis — a completely unrelated target — and retains activity against many fluoroquinolone-resistant E. coli. Fosfomycin is approved as a single-dose oral treatment for uncomplicated UTI.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.