Fluoroquinolones

Summary

Fluoroquinolones are a group of antibiotics that end with the suffix “-floxacin”, including Ciprofloxacin, Moxifloxacin, or Levofloxacin. These drugs work by inhibiting the enzymes, DNA gyrase and topoisomerase IV, which are both enzymes used to wind and unwind bacterial DNA for replication and transcription. Blocking these enzymes impairs bacterial DNA function, which has a bactericidal effect on most bacteria. Clinically, fluoroquinolones are broad-spectrum antibiotics used for a variety of bacterial infections. One of the most important side effects of fluoroquinolones is tendonitis and tendon rupture. Fluroquinolones should not be taken with antacids, as antacids will prevent the GI absorption of fluoroquinolones, preventing them from entering the body to exert their antibiotic activity. Fluoroquinolones should also be avoided in pregnant women and children due to the potential of causing skeletal defects in teeth and bone. One fluoroquinolone drug in particular, ciprofloxacin, is a potent inhibitor of CYP enzymes and is well known to cause drug interactions. Last but not least, remember that fluoroquinolones can cause QT prolongation, increasing the risk of Torsades de Pointes.

Key Points

• Fluoroquinolones
  • Drug Names
    • Ciprofloxacin
    • Levofloxacin, Moxifloxacin, Gemifloxacin
      • “Respiratory” fluoroquinolones used for pneumonias
    • Enoxacin
    • Norfloxacin
    • Ofloxacin
  • Mechanism
    • Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
      • Inhibits bacterial DNA synthesis by inhibiting DNA winding and unwinding, which causes strand breaks
    • Bactericidal
    • Must not be taken with antacids
      • Reduces oral absorption of drug, reducing its efficacy
  • Clinical Use
    • Gram-negative rods
      • In urinary and GI tracts (e.g. Pseudomonas)
    • Some gram-positive organisms
    • Otitis externa
  • Adverse Effects
    • Tendonitis/Tendon rupture
      • e.g. Achilles tendon rupture
    • Teratogen
      • Possible cartilage damage
    • Avoid in children
      • Possible cartilage damage
    • Ciprofloxacin: Inhibits CYP450 enzymes
      • Can lead to drug interactions (e.g. warfarin, theophylline)
    • Prolongs QT interval (Torsades de Pointes risk)
    • GI upset
    • Superinfections
    • Skin rashes
    • Headache, Dizziness
    • Leg cramps, myalgias
  • Resistance
    • Mutation in DNA gyrase/topoisomerase genes
    • Plasmid-mediated resistance
    • Efflux pumps