Synergy of flavone with vancomycin and oxacillin against vancomycin-intermediate Staphylococcus aureus

ABSTRACT

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 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-dependant 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