Clinical use of the fluoroquinolones

Abstract

The appetite for modification to the basic quinolone nucleus has grown logarithmically since the first quinolone was employed in clinical practice. Important structural refinements have led to expanded microbiologic activity, optimal pharmacokinetics, and increased safety profiles. The practicing clinician and researcher may glean considerable information from the quinolone structure with regard to microbiologic spectra and safety before administering these agents to patients. Although some toxicities can be ominously predictable, such as with the so-called high-risk quinolones (e.g., double-halogenated and trifluorinated quinolones), clinicians must rely on animal models of toxicity and clinical trial data to discern other toxicities (e.g., Q-Tc interval prolongation). A few quinolones enjoy a relatively clean safety profile and are well tolerated (e.g., gatifloxacin, levofloxacin, ciprofloxacin). Other quinolones may be associated with significant collateral system toxicity during therapy; however, under certain conditions, albeit rare, their potential for benefit may outweigh the existing risk. Clinafloxacin, for use in the management of lung infections caused by multiply resistant B. cepacia in cystic fibrosis patients, is an example of a risk that may be outweighed by its therapeutic benefit. Because there are many treatment alternatives within the clinician's armamentarium, the obligation is to select the safest, most therapeutically effective, and most cost-effective agent that is available. In addition to increasing mortality and morbidity, the development of toxicity or an adverse event during therapy may compromise the immediate effectiveness of treatment as well as affect the cost of the patient's care significantly. With the immediate abundance of quinolones available for use, the safest, most effective, and best-tolerated agents will likely emerge as the most appropriate therapeutic choices when a quinolone is indicated.