Fluoroquinolones

One-Sentence Definition

Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV, providing broad Gram-negative (and some Gram-positive) activity — with chromosomal resistance common and significant toxicity/t stewardship concerns.

Simple Explanation

They block DNA replication enzymes — good for many urinary and respiratory Gram-negatives when susceptible, but resistance rises fast.

Detailed Scientific Explanation

Agent (examples)Notes
CiprofloxacinPseudomonas-capable (context); GI/UTI
LevofloxacinRespiratory Gram-positives/negatives (when susceptible)
MoxifloxacinAnaerobic/atypical coverage nuances

Spectrum: Enterobacterales, Pseudomonas (cipro), atypicals (Legionella, Mycoplasma) — always check local AST.

Resistance: gyrA/parC mutations; plasmid-mediated qnr (low-level); efflux — often multi-step.

Toxicities: tendon rupture, QT prolongation, CNS effects, glucose dysregulation — affects empiric use.

Mechanism

Trap gyrase/topoisomerase on DNA → double-strand breaks → bactericidal effect (concentration-dependent).

Clinical Importance

  • Uncomplicated cystitis options where susceptibility known
  • Not reliable empiric therapy for Gonorrhea (widespread resistance)
  • TB (ofloxacin/moxifloxacin) in MDR regimens — specialized use

AMR Relevance

  • Selects rapidly in E. coli UTIs and Campylobacter (One Health)
  • Part of MDR/XDR Typhoid and Enterobacterales profiles

Active Recall Questions

  1. Primary enzymatic targets?
  2. Why avoid FQ for gonorrhea empirically?
  3. Concentration-dependent killing — dosing implication?

Connections