Activity and synergistic interactions of stilbenes and antibiotic combinations against bacteria in vitro

The synergistic antibacterial activity of two stilbenes [3,4',5-trihydroxystilbene (1) and 3,5-dihydroxy-4-isopropylstilbene(2)] purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) in combination with ciprofloxacin and cefotaxime was investigated. The activity of the stilbenes and standard antibiotics on bacteria were determined using the macrodilution method. The minimum inhibitory concentration and minimum bactericidal concentration of the stilbenes was compared with that of the standard antibiotics. The antibacterial activities of stilbenes against pathogenic bacteria were assessed using the checkerboard and time-kill methods to evaluate the synergistic effects of stilbenes in treatment with ciprofloxacin or cefotaxime. The results of the present study showed that the combination effects of both stilbenes with ciprofloxacin were synergistic (FIC index <0.5). Whereas stilbene 2 with cefotaxime recorded additive. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 12-24 h of treatment with 50:50 ratios of stilbenes and antibiotics. These results suggest that stilbenes combined with antibiotics may be microbiologically beneficial and not antagonistic. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and stilbenes). The in vitro synergistic activity of stilbenes and antibiotics against bacteria is reported here for the first time.