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J Antimicrob Chemother. 1986 Nov;18 Suppl D:21-9.

The mode of action of 4-quinolones and possible mechanisms of resistance.


Supercoiling of bacterial DNA, mediated by DNA gyrase, is essential to enable bacteria to accommodate their very long chromosomes within the cell envelope. Bacterial DNA gyrase, unlike the comparable mammalian enzyme, is susceptible to 4-quinolone antimicrobials. All 4-quinolones share this action, but ciprofloxacin, norfloxacin and ofloxacin possess an additional killing mechanism which vastly increases their potency. The occurrence of this second mechanism may also explain the lower frequencies (in populations of Escherichia coli KL 16) of mutants resistant to these three quinolones (less than 10(-12)) compared with other quinolones (10(-10)-10(-8)). No mutant was encountered that was resistant to peak serum concentrations of ciprofloxacin, norfloxacin or ofloxacin, or resistant to attainable urine concentrations of these or of acrosoxacin, flumequine, enoxacin, oxolinic acid or pipemidic acid. Mutational resistance may not necessarily lead to therapeutic resistance to 4-quinolones in E. coli.

[Indexed for MEDLINE]

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