Synergy of flavone with vancomycin and oxacillin against vancomycin-intermediate Staphyloccus aureus.
This study evaluated in vitro activity of 9 flavonoids in combination with vancomycin or oxacillin against vancomycin-intermediate Staphylococcus aureus (VISA) ATCC 700699 by employing the checkerboard method to obtain Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index. Six flavonoids namely hesperitin, rutin, naringenin, flavones, naringin and 3, 7-dihyroxyflavone which exhibited notable inhibitory activity (MIC values < 3200 μg/ml) were further evaluated for combination assay with antibiotics. The combinations of vancomycin+flavone and oxacillin+flavone were found synergistic with the FIC index value 0.094 and 0.126, respectively. Other combinations showed an additive interaction (FIC index = 1.063) but no antagonistic reaction (FIC index > 4) were observed. In time kill studies, oxacillin-flavone combination at synergistic concentration demonstrated bactericidal effect at 24 h period with concentration-dependent manner on the VISA strain. Following 1 h exposure, the combination also produced persistent effect on the bacteria growth for 2.9 hrs at 1x sub-MIC and more than 24 h at 5x of sub-MIC and there was a significant difference between both concentrations (p<0.05). Vancomycin-flavone combination, however, showed no concentration-dependent effect and lower PAE values (1.159 h and 2.322 h at 1x and 5x sub-MIC, respectively) on the VISA strain. In conclusion, flavone markedly intensifies the susceptibility of oxacillin against VISA and the combination can be implicated for further interaction studies at molecular level.
Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Nur Salwani
NS
Bakar
Noraziah Mohamad
NM
Zin
Dayang Fredalina
DF
Basri
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005419:Flavonoids; D014640:Vancomycin; D010068:Oxacillin