Mechanisms of resistance to fluoroquinolones

Fluoroquinolones have some of the properties of an 'ideal' antimicrobial ag ent. Because of their potent broad spectrum activity and absence of transfe rable mechanism of resistance or inactivating enzymes, it was hoped that cl inical resistance to this useful group of drugs would not occur, However, o ver the years, due to intense selective pressure and relative lack of poten cy of the available quinolones against some strains, bacteria have evolved at least two mechanisms of resistance: (i) alteration of molecular targets, and (ii) reduction of drug accumulation. DNA gyrase and topoisomerase IV a re the two molecular targets of fluoroquinolones. Mutations in specified re gions (quinolone resistance-determining region) in genes coding for the gyr ase and/or topoisomerase leads to clinical resistance. An efflux pump effec tive in pumping out hydrophilic quinolones has been described. Newer fluoro quinolones which recognize both molecular targets and have improved pharmac okinetic properties offer hope of higher potency, thereby reducing the prob ability of development of resistance.