quinolone

Quinolone is a class of synthetic antimicrobial agents that are based on the 4-quinolone core structure. The term encompasses older nonfluorinated compounds such as nalidixic acid, as well as newer fluoroquinolones that carry fluorine substitutions and other modifications. Clinically important fluoroquinolones include ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, and delafloxacin. Quinolones are used to treat a range of infections and are available in oral and intravenous forms.

Mechanism of action and spectrum: Quinolones inhibit bacterial DNA gyrase (topoisomerase II) and, in many species, topoisomerase IV, enzymes essential for DNA replication and transcription. This leads to bactericidal activity, with killing that is often concentration-dependent. They have broad activity against many Gram-negative bacteria and, in later generations, increased activity against certain Gram-positive and atypical pathogens. Activity against anaerobes is more limited and varies by agent.

Pharmacology and safety: Quinolones generally offer good oral bioavailability and tissue penetration, making them convenient for a variety of infections, including respiratory and urinary tract infections. Adverse effects can include tendinopathy and tendon rupture, QT interval prolongation, hypoglycemia or hyperglycemia, CNS effects, and hypersensitivity. They are cautioned or avoided in pregnancy and in children for certain agents due to potential cartilage toxicity. Interactions with divalent cations and certain supplements can reduce absorption. Regulatory agencies warn about serious risks, contributing to more restricted use.

Resistance and clinical use: Resistance mechanisms include mutations in gyrA/gyrB and parC/parE, efflux pumps, and plasmid-mediated qnr genes. Because of safety concerns and rising resistance, guideline-directed use emphasizes targeted therapy when possible. Quinolones are used for various urinary, respiratory, gastrointestinal, and some skin and intra-abdominal infections, but many guidelines discourage routine use for uncomplicated cases when safer alternatives exist.