Resistance to quinolones in gram-negative microorganisms: mechanisms and prevention.

Bacterial resistance to quinolones is essentially the result of mutations on several genes involved in the synthesis of DNA-gyrase or in proteins of the cellular envelope. A single mutational event may lead to complete resistance to older quinolones, but clinical resistance to newer quinolones such as norfloxacin requires two or more mutations. Prevention of resistance to norfloxacin requires prevention of the strains carrying 'first mutations' (by a controlled use of older quinolones) and the early detection of such strains. If microbiologic and pharmacologic data are taken into account at the same time, the incidence of norfloxacin-resistant strains in urinary tract infections will remain insignificant.