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Fluoroquinolones: Classification, Mechanism of Action, Resistance, and Therapeutic Uses
Classification of Fluoroquinolones
- First-generation: Nalidixic acid
- Second-generation: Ciprofloxacin, ofloxacin
- Third-generation: Levofloxacin, moxifloxacin
- Fourth-generation: Gemifloxacin, delafloxacin
Mechanism of Action
Fluoroquinolones inhibit DNA gyrase and topoisomerase IV, enzymes responsible for DNA replication. This leads to DNA fragmentation and bacterial cell death.
Mechanism of Resistance
- Mutations in DNA gyrase or topoisomerase IV reduce drug binding.
- Efflux pumps expel the drug from bacterial cells.
- Reduced permeability of bacterial membranes to fluoroquinolones.
- Plasmid-mediated resistance with altered targets or efflux systems.
Therapeutic Uses
- Urinary tract infections (UTIs): Ciprofloxacin
- Respiratory infections: Levofloxacin for pneumonia, chronic bronchitis
- Gastrointestinal infections: Ciprofloxacin for traveler's diarrhea
- Skin and soft tissue infections: Delafloxacin for MRSA
- Bone and joint infections: Ciprofloxacin for osteomyelitis
- Atypical infections: Moxifloxacin for Legionella, Mycoplasma
Adverse Effects
- Gastrointestinal: Nausea, vomiting, diarrhea
- CNS: Headache, dizziness, confusion, seizures
- Tendonitis, tendon rupture
- QT interval prolongation, arrhythmias
- Phototoxicity
- Hepatotoxicity, peripheral neuropathy
Contraindications
- Pregnancy and breastfeeding
- Children under 18 years
- History of tendonitis or tendon rupture
- Hypersensitivity to fluoroquinolones
- Severe renal impairment
- Concomitant use with corticosteroids
