A patient on fluoroquinolone therapy for Pseudomonas bacteremia develops treatment failure. Susceptibility testing reveals high-level fluoroquinolone resistance. Which molecular mechanism is most likely responsible?
- A Production of carbapenemase enzymes that degrade fluoroquinolones
- B MRSA-like mecA gene acquisition altering the target
- C Mutation in gyrA gene (Ser83Leu substitution) reducing DNA gyrase binding affinity for fluoroquinolones ✓
- D Mutation in erm gene causing ribosomal methylation
Correct answer: C. Mutation in gyrA gene (Ser83Leu substitution) reducing DNA gyrase binding affinity for fluoroquinolones
Explanation
Fluoroquinolone resistance in Pseudomonas and other Gram-negatives most commonly results from point mutations in gyrA (encoding DNA gyrase subunit A) at positions Ser83 and Asp87, reducing drug binding to the topoisomerase-DNA complex. Secondary mutations in parC (topoisomerase IV) further increase resistance. Efflux pump overexpression (MexAB-OprM) and porin loss also contribute. Options B, C, and D describe unrelated resistance mechanisms for carbapenems, beta-lactams, and macrolides respectively.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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