The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro.

TLDR: The status of these agents as revealed in the published English literature is reviewed in a two-part minireview, considering the structures, mechanisms of action and resistance, and spectra of activity of the six aforementioned fluoroquinolones with reference to nalidixic and oxolonic acids.

Abstract: INTRODUCTION During the past 5 to 7 years, much attention has been given to the synthesis of new 4-quinolone-3-carboxylates and to the evaluation of these newly prepared agents for antibacterial activity, a revival of interest generated by the discovery of nalidixic and oxolinic acids mtny years ago. This renewed effort uncovered a. number of 6-fluoro-7piperazino-4-quinolones noteworthy for both the breadth and intensity of their activities against gram-negative bacilli and cocci in vitro and for the capacity to control experimentally induced systemic infections with selected bacteria when administered orally in well-tolerated doses (21). The most active representatives of this compound class, designated fluoroquinolones, include norfloxacin (AM-715, MK-0366), ofloxacin (DL-8280), ciprofloxacin (Bay o 9867), amifloxacin (WIN 49375), enoxacin (AT-2266, CI-919), and pefloxacin (1589-RB). The prim4ary target of nalidixic acid and probably also all the fluoroquinolones is DNA gyrase, an essential bacterial enzyme that maintains superhelical twists in DNA (13, 18, 24). The promise of the fluoroquinoloies led to their prompt evaluation for pharmacokinetics in human volunteers and cautious assessments of therapeutic potential, including tolerability in selected patients. The encouraging results of these early trials, with the burgeoning interest in further studies, have made it desirable to review the status of these agents as revealed in the published English literature. We have attempted this task in a two-part minireview. The first part here considers the structures, mechanisms of action and resistance, and spectra of activity of the six aforementioned fluoroquinolones with reference to nalidixic and oxolonic acids for comparison. The second part will consider pharmacology, clinical activity, and toxicities in humans (D. C. Hooper and J. S. Wolfson, Antimicrob. Agents Chemother., in press). Other quinolones, such as cinoxacin, pipemidic acid, rosoxacin, and flumequine, will not be discussed directly. Several reviews of cinoxacin have recently appeared (28, 63).