Fluoroquinolones are an important class of wide‐spectrum antibacterial agents. The first
quinolone described was nalidixic acid, which showed a narrow spectrum of activity. The
evolution of quinolones to more potent molecules was based on changes at positions 1, 6, 7
and 8 of the chemical structure of nalidixic acid. Quinolones inhibit DNA gyrase and
topoisomerase IV activities, two enzymes essential for bacteria viability. The acquisition of
quinolone resistance is frequently related to (i) chromosomal mutations such as those in the …

A topoisomerase was identified as the bacterial target site for quinolone action in the late
1970s. Since that time, further study identified two bacterial topoisomerases, DNA gyrase
and topoisomerase IV, as sites of antibacterial activity. DNA gyrase appears to be the
primary quinolone target for gram‐negative bacteria. Topoisomerase IV appears to be the
preferential target in gram‐positive organisms, but this varies with the drug. Three
mechanisms of resistance against quinolones are mutations of topoisomerases, decreased …