fluoroquinolones

Fluoroquinolones are a class of broad-spectrum antibacterial agents that inhibit bacterial DNA replication by targeting DNA gyrase (gyrA/gyrB) and topoisomerase IV. They are bactericidal and have activity against many gram-negative aerobes and several gram-positive cocci, as well as atypical pathogens such as Mycoplasma and Chlamydophila. Activity against anaerobes is variable and often limited, depending on the agent.

Common agents include ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, norfloxacin, gemifloxacin and delafloxacin.

Clinical use covers a broad range of infections, including complicated and uncomplicated urinary tract infections and prostatitis; community-acquired pneumonia and other respiratory infections; skin and soft tissue infections; intra-abdominal infections (often in combination); gonorrhea; and post-exposure prophylaxis for anthrax.

Pharmacology: oral bioavailability is high for most agents; tissue penetration is good in urine, prostate, lungs, and skin. Dosing often adjusted for renal impairment; hepatic metabolism occurs for some agents. Absorption is reduced by dairy or multivitamins containing divalent cations; separate dosing recommended.

Safety: fluoroquinolones carry risks of tendinopathy and tendon rupture, peripheral neuropathy, CNS effects, QT interval prolongation, dysglycemia, phototoxicity, and C. difficile infection. Should be avoided in myasthenia gravis and with caution in the elderly, in pregnancy and in children.

Resistance: common mechanisms include mutations in gyrA/gyrB and parC, as well as efflux pumps and, for some agents, plasmid-mediated qnr genes. Overuse accelerates resistance.

Regulatory and stewardship notes: many agencies advise limiting fluoroquinolone use to specific indications where benefits outweigh risks, and to avoid use for uncomplicated infections when safer alternatives exist.

Generations vary in spectrum: earlier agents favor gram-negatives; newer ones expand gram-positives and atypicals, with moxifloxacin offering broader anaerobic activity but limited urinary excretion; delafloxacin is a newer agent with expanded Gram-positive coverage.