Quinolone generations: natural history or natural selection?

The quinolones have evolved from antibacterial agents with a limited spectr um of predominantly anti-Gram-negative antimicrobial activity and a restric ted number of indications to a class of widely used oral land, in some case s, intravenous) antibiotics with extensive indications for infections cause d by many bacterial pathogens in most body tissues and fluids. This evoluti onary pattern has arisen through the development of new core and side-chain structures, with associated improvements in activity, pharmacokinetics and tolerability, and through the selection of molecules that remain useful an d well tolerated. This review describes the progress of the quinolones from the first to the third (IIIa and IIIb) generations. Special attention is g iven to gemifloxacin, currently the most developmentally advanced third-gen eration quinolone, which has enhanced in vitro Gram-positive antimicrobial activity and no troublesome adverse drug reactions. Preliminary data indica te that gemifloxacin should prove to be an important addition to the fluoro quinolone class. Further clinical trial data are awaited with interest.