Fluoroquinolones

The era of quinolone antibiotics began with the serendipitous discovery of the prototype quinolone antibiotic, nalidixic acid, during the synthesis of the antimalarial agent, chloroquine, in the early 1960s.(50) Nalidixic acid never became a useful agent to treat systemic infections because of its narrow antibacterial spectrum, poor tissue penetrability, rapid emergence of bacterial resistance, and frequent adverse central nervous system (CNS) effects(72); however, nalidixic acid did provide the chemical foundation upon which to build the modifications that subsequently would improve therapeutic properties and limit adverse effects of the quinolones. To date more than 10,000 analogues of nalidixic acid have undergone an initial screening process. More than 20 years passed, however, before such an analogue, the first fluoroquinolone (FQ) antibiotic, was approved for clinical use. Over the last decade, the FQs have become a dominant class of antimicrobial agents. No other class of antimicrobial agents has grown so rapidly or been developed with such interest by pharmaceutical research companies. Through the 1990s and into the new millennium, this drug class will likely double in size, with several approvals currently before the Food and Drug Administration (FDA) in the United States. In the past 3 years, four new agents have been released into the US market, including levofloxacin, sparfloxacin, grepafloxacin, and trovafloxacin. Moxifloxacin and gatifloxacin are two additional FQs that have been recently approved for use. Clinafloxacin, gemafloxacin, and tosufloxacin are on the horizon. With the rapid expansion of the FQs comes the potential for confusion regarding appropriate use, tolerability, safety profiles, drug interactions, and dosing issues. This review provides an overview of the FQ class including mechanisms of action and emerging resistance, spectrum of activity, and pharmacology, paying particular attention to the newer agents. In addition, we provide a clinically relevant overview of use of these agents.