Cooperative Behavior of Fluoroquinolone Combinations against Escherichia coli and Staphylococcus aureus

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 the...

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Bibliographic Details
Published in:	Biological & pharmaceutical bulletin Vol. 40; no. 6; pp. 758 - 764
Main Authors:	Vitorino, Graciela Pinto, Becerra, María Cecilia, Barrera, Gustavo Daniel, Caira, Mino Rodolfo, Mazzieri, María Rosa
Format:	Journal Article
Language:	English
Published:	Japan The Pharmaceutical Society of Japan 2017 Pharmaceutical Society of Japan Japan Science and Technology Agency
Subjects:	Anti-Bacterial Agents - pharmacology Antibiotics Assaying Ciprofloxacin combination cooperative behavior Drug Synergism E coli Escherichia coli - drug effects Escherichia coli - growth & development fluoroquinolone Fluoroquinolones - pharmacology Microbial Sensitivity Tests Minimum inhibitory concentration Norfloxacin Reactive oxygen species sinergistic effect Staphylococcus aureus - drug effects Staphylococcus aureus - growth & development fluoroquinolone sinergistic effect norfloxacin cooperative behavior ciprofloxacin combination
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Summary:	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 the more effectives combinations against Escherichia coli were 0.0009 µg/mL CIP+0.0312 µg/mL NOR and 0.0037 µg/mL CIP+0.0075 µg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 µg/mL CIP+0.2500 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 combinations 0.0009 µg/mL CIP+0.0312 µg/mL NOR, 0.0018 µg/mL CIP+0.0312 µg/mL NOR, 0.0037 µg/mL CIP+0.0075 µg/mL NOR and 0.0037 µg/mL CIP+0.0156 µg/mL NOR at 24 h against E. coli. The combination 0.0037 µg/mL CIP+0.0312 µg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidal effects at 4 h. The combinations 0.0625 µg/mL CIP+0.2500 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 minimum inhibitory concentration (MIC) CIP+1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecular of CIP and NOR assayed, generated less levels of reactive oxygen species (ROS) than the components alone.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0918-6158 1347-5215
DOI:	10.1248/bpb.b16-00616