## Mechanism and Spectrum of Fluoroquinolones ### Correct Statements **Key Point:** Fluoroquinolones are **bactericidal** agents that inhibit bacterial topoisomerases, preventing DNA supercoiling and subsequent replication and transcription. **High-Yield:** The two primary targets are: - **DNA gyrase (topoisomerase II)** — primarily in gram-negative bacteria - **Topoisomerase IV** — primarily in gram-positive bacteria Newer fluoroquinolones (moxifloxacin, gemifloxacin) have improved activity against gram-positive organisms, including *Streptococcus pneumoniae*, due to enhanced topoisomerase IV inhibition. ### Why Option 1 Is Incorrect **Warning:** This is the **wrong statement**. Gram-negative bacilli (e.g., *E. coli*, *Pseudomonas aeruginosa*, *Klebsiella*) are **more susceptible** to fluoroquinolones than gram-positive cocci. Early fluoroquinolones were primarily gram-negative agents. Gram-positive coverage improved only with later-generation agents. ### Comparative Susceptibility | Organism Class | Susceptibility | Notes | |---|---|---| | Gram-negative bacilli | **Excellent** | DNA gyrase is primary target; early FQs were gram-negative agents | | Gram-positive cocci | **Moderate–Good** (older FQs) → **Good** (newer FQs) | Topoisomerase IV is primary target; moxifloxacin > ciprofloxacin | | *Pseudomonas aeruginosa* | **Good** (ciprofloxacin) | Fluoroquinolone of choice for *P. aeruginosa* | | *Streptococcus pneumoniae* | **Poor** (older FQs) → **Good** (moxifloxacin) | Newer agents better for respiratory infections | [cite:KD Tripathi 8e Ch 48]
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