Resistance to fluoroquinolones in Gram-negative bacteria most commonly arises through mutations in which specific target, and which quinolone target does it preferentially affect?

• A Porin channel mutation; affects entry of all fluoroquinolones equally
• B Mutations in parC gene encoding topoisomerase IV; affects topoisomerase IV preferentially in Gram-negative organisms
• C Acquisition of qnr plasmid genes encoding proteins that protect DNA gyrase; completely abrogates activity
• D Mutations in gyrA gene encoding DNA gyrase subunit A; affects gyrase preferentially in Gram-negative organisms ✓

Explanation

In Gram-negative bacteria, the primary target of fluoroquinolones is DNA gyrase (topoisomerase II), and mutations in the gyrA gene (encoding the A subunit of DNA gyrase) are the most common first-step resistance mutations. In Gram-positive organisms, topoisomerase IV (encoded by parC/parE) is the primary target, and mutations there are the first step in resistance. Plasmid-mediated resistance via qnr genes does occur and provides protection but confers only low-level resistance; it is not the most common mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.