A Staphylococcus aureus blood culture isolate shows a rising ciprofloxacin MIC over successive admissions. The single most important chromosomal mechanism responsible for high-level fluoroquinolone resistance in gram-positive cocci is:
- A Point mutations in the QRDR of gyrA and grlA reducing drug binding to topoisomerases ✓
- B Acquisition of a plasmid-encoded qnr gene
- C Production of aminoglycoside acetyltransferase
- D Loss of the vanHAX gene cluster
Correct answer: A. Point mutations in the QRDR of gyrA and grlA reducing drug binding to topoisomerases
Explanation
Fluoroquinolone resistance develops stepwise through point mutations in the quinolone-resistance-determining region (QRDR) of the target subunits, chiefly GyrA of DNA gyrase and GrIA (ParC equivalent) of topoisomerase IV in staphylococci. Mutated targets bind the drug less avidly while retaining catalytic function. qnr plasmids mainly protect gyrase in gram-negatives, and enzymatic drug modification does not apply to quinolones.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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