Cooperative Behavior of Fluoroquinolone Combinations against Escherichia coli and Staphylococcus aureus

PINTO VITORINO G; BECERRA M.C,; BARRERA GD; CAIRA M; MAZZIERI MR

BIOL. PHARM. BULL.

PHARMACEUTICAL SOC JAPAN

Lugar: Tokyo; Año: 2017 vol. 40

0918-6158

The effects of different combinations of ciprofloxacin (CIP) and norfloxacin (NOR) against Escherichia coli and Staphylococcus aureus were studied using checkerboard, fractional inhibitory concentration (FIC) and time?kill analysis methods. Results obtained by the checkerboard method showed that themore effectives combinations against Escherichia coli were 0.0009 μg/mL CIP0.0312 μg/mL NOR and 0.0037 μg/mL CIP0.0075 μg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 μg/mL CIP0.2500 μg/mL NOR showed a synergistic effect, with a FIC index of 0.50. The results of the time?kill method demonstrated either indifference or additivity of the ombinations 0.0009 μg/mL CIP0.0312 μg/mL NOR, 0.0018 μg/mL CIP0.0312 μg/mL NOR, 0.0037 μg/mL CIP 0.0075 μg/mL NOR and 0.0037 μg/mL CIP0.0156 μg/mL NOR at 24 h against E. coli. The combination 0.0037 μg/mL CIP0.0312 μg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidaleffects at 4 h. The combinations 0.0625 μg/mL CIP0.2500 μg/mL NOR and 0.0625 μg/mL CIP 0.0625 μg/mL NOR showed indifference or additivity against S. aureus. None of them generated bactericidal effect at 4 h.Moreover, this last equimolecular combination (equivalent to 1/4 minimal inhibitory concentration (MIC)CIP1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecularof CIP and NOR assayed, generated less levels of reactive oxygen species(ROS) than the components alone.