Combination of ferulic acid and antibiotics as effective antibacterial agents

Ferulic acid (FA) is a monophenolic phenyl propanoid occurring in plant materials including rice, green tea and coffee beans. In this study we have shown that FA interacts in a synergistic way with antibiotics such as amikacin, ampicillin, ciprofloxacin, erythromycin and vancomycin against Gram negative (Escherichia coli, Enterobacter aerogenes and Pseudomonas aeruginosa) and positive (Staphylococcus aureus) bacteria. The interaction is quantified by checkerboard and time-kill curve assays. The Fractional Inhibitory Concentration (FIC) index shows that FA is synergistic with amikacin against all the organisms, except P. aerugionsa (see Table below). S.aureus was found to be highly sensitive to the combinations and P.aeruginosa was the least. Time kill curve studies was done to study the parameters such as killing rate (K_max) and area under killing curve (AURKC) for the combinations, namely phytochemical and antibiotics and were compared with the values from individual compounds. The K_max and AURKC for FA and amikacin combination against E.coli was –2.7h-1 and –15.6 respectively and was statistically significant than the individual treatments. FA possessed bacterial membrane damaging activity. Our study showed that FA was synergistic with few of the antibiotics tested; therefore food rich in this natural compound could positively interact with antibiotics under in vivo conditions too.

Table 1: FIC index indicating the interaction of FA with antibiotics against various bacteria. (Synergy is indicated by underline)

	Microorganisms
Phytochemical	E. coli					E. aerogenes
	Ami	Amp	Cip	Ery	Van	Ami	Amp	Cip	Ery	Van
FA	0.38	0.62	0.47	0.48	0.52	0.18	0.76	0.52	0.51	0.68

	Microorganisms
Phytochemical	P. aeruginosa					S. aureus
	Ami	Amp	Cip	Ery	Van	Ami	Amp	Cip	Ery	Van
FA	0.54	0.68	0.49	0.73	0.66	0.16	0.65	0.36	0.44	0.23