4-Quinolone interactions with gyrase subunit B inhibitors

In studies which have involved determination of fractional inhibitory concentrations, synergy has been described between the 4-quinolones, which inhibit the A subunit of DNA gyrase, and either coumermycin or novobiocin, which inhibit the B subunit of the same enzyme. In this study, fixed concentrations of ciprofloxacin or ofloxacin were combined with varying concentrations of coumermycin or novobiocin and vice versa in nutrient broth. The bactericidal activities of the different mixtures against either Staphylococcus aureus E3T or S. warneri were determined and found to be less than those of equivalent concentrations of either 4-quinolone alone. The observation that gyrase B subunit inhibitors antagonised the bactericidal activity of 4-quinolones is in accordance with the report previously made by others that ciprofloxacin combined with coumermycin was less effective than ciprofloxacin alone in treating staphylococcal endocarditis in rats. Our results indicate that both inhibitory and bactericidal activity should be taken into account when assessing possible interactions in vivo between 4-quinolones and other antimicrobial agents.