Antibiotic-phytochemical combinations against Enterococcus faecalis: a therapeutic strategy optimized using response surface methodology.

Enterococcus faecalis, a Gram-positive bacterium that causes nosocomial infections, has been reported to be resistant to several antibiotics, posing a significant threat to public healthcare. In the present study, we explored a combinatorial therapeutic approach involving conventional antibiotics alongside phytochemicals against E. faecalis. Vancomycin and ciprofloxacin were chosen for the current study due to their different modes of action. The minimum inhibitory concentration (MIC) of cuminaldehyde and thymoquinone was found to be 500 µg/mL and 30 µg/mL, respectively. Co-administering vancomycin with thymoquinone or cuminaldehyde reduced the MIC of vancomycin from 5 to 2 µg/mL, resulting in a 60% drop in MIC dose. Ciprofloxacin's MIC reduced from 1.5 to 1 µg/mL in the presence of the same phytochemicals, resulting in 33% reduction in its MIC dose. Furthermore, fractional inhibitory concentration indices (FICI) suggested additive interactions (FICI range: 0.66-1) between the antibiotics and phytochemicals against E. faecalis. Since precision dosing is important for any combinatorial application, we explored response surface methodology (RSM) to optimize dosing regimens of the selected compounds. It was observed that the predicted optimal concentrations of the test compounds (in different combinations) could closely match the actual observations when tested under the in-vitro laboratory conditions (R2 range: 0.97-0.99). These findings suggested that combining conventional antibiotics with phytochemicals may offer a promising strategy to enhance the antimicrobial efficacy for effective control of infections caused by E. faecalis.