Clinical use of the fluoroquinolones

The quinolones have undergone a "structural evolution" since the inadverten t discovery of nalidixic acid in 1962. A better understanding of structure- activity and structure-toxicity relationships has allowed chemists to modif y the adaptable quinolone structure to enhance or limit the extent of antim icrobial activity and to improve various other product attributes such as t he pharmacokinetic profile, tolerability, drug interaction potential, and t oxicity of each new agent. Ciprofloxacin and levofloxin/ oflofloxin have de monstrated relatively clean safety profiles over several years of clinical use. Newer fluorquinolones should be fully evaluated by clinicians prior to their use so as to avoid potentially life-threatening adverse events. Seve ral newer quinolones are available or are being investigated for clinical u se, including gatifloxacin, moxifloxican, clinafloxacin, and gemifloxacin. Rare but life-threatening toxicities (e.g., cardiotoxicity, hepatotoxicity) have led to the withdrawal or have severely limited the use of two quinolo nes, grepafloxacin and trovafloxacin, in 1999. We review the clinical use o f the quinolones, including the role of newer generation fluoroquinolones a nd their place in therapy, transitional therapy principles, and issues conc erning safety and toxicity.