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Journal of Antimicrobial Chemotherapy (1999) 43, Suppl. B, 31-37
© 1999 The British Society for Antimicrobial Chemotherapy

The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus

Holger Schedletzky, Bernd Wiedemann and Peter Heisig*

Pharmaceutical Microbiology, University of bonn, Meckenheimer Allee 168, D-53115 Bonn, Germany

The effect of moxifloxacin on its target enzymes was evaluated by three different approaches: (i) the MICs of moxifloxacin and nine other fluoroquinolones were determined for mutants of Escherichia coli (n = 13) and Staphylococcus aureus (n = 5) carrying different combinations of resistance mutations; (ii) the activity of moxifloxacin on isolated targets was determined as IC 50 values for wild-type and mutant type II topoisomerases from E. coli; and (iii) the mutation frequencies were determined for two single-step mutants (MI with a Ser83->Leu mutation in gyrA and WT-4 with a Ser80->Ile mutation in parC) and their parent strain (WT). Of the quinolones tested, moxifloxacin was the only one showing an equivalent high activity against both targets. This is reflected by a comparable high susceptibility of the test strains of E. coli and S. aureus and by the IC 50 values of moxifloxacin which were 50–90% lower than those of ciprofloxacin, norfloxacin and sparfloxacin for the wild-type and single mutant enzymes of gyrase and topoisomerase IV. However, double mutant GyrA was significantly more sensitive to moxifloxacin than to the other fluoroquinolones tested, while wild-type topoisomerase IV was two-fold more refractory. Mutation rates of WT, MI and WT-4 for ciprofloxacin and moxifloxacin were 5 x 10-8 vs 4 x 10-10, <6 x 10-11 vs <6 x 10-11; and 2 x 10 -6 vs 5 x 10-7, respectively. These data indicate an equivalenthigh inhibitory activity of moxifloxacin on DNA gyrase and topoisomerase IV of E. coli.

* Corresponding author. Tel: +49-228-735267.


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