Fluoroquinolones such as ciprofloxacin kill bacteria primarily by which mechanism?

• A Inhibiting bacterial RNA polymerase, blocking transcription initiation
• B Blocking the 50S peptidyl-transferase center, preventing peptide elongation
• C Stabilizing the DNA-topoisomerase II/IV cleavable complex, causing irreversible double-strand DNA breaks ✓
• D Inhibiting dihydrofolate reductase, depleting tetrahydrofolate

Explanation

Fluoroquinolones inhibit bacterial DNA gyrase (topoisomerase II, primary target in gram-negatives) and topoisomerase IV (primary target in gram-positives) by forming a ternary drug-enzyme-DNA cleavable complex. This complex stabilizes cut DNA strands in a cleaved intermediate state, and the drug prevents relegation, resulting in double-strand breaks that are bactericidal. RNA polymerase is the target of rifampicin. The 50S peptidyl-transferase center is targeted by chloramphenicol and linezolid. DHFR is inhibited by trimethoprim.

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

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