Antibacterial Activity of Estragole From Ocimum tenuiflorum , and Tagetes lucida and Synergistic Effect With Meropenem and Tobramycin Against Multidrug‐ and Extensively Drug‐Resistant (MDR‐XDR) Gram‐Negative Bacteria

Estragole, a prime compound present in the essential oils (EOs) of Ocimum tenuiflorum and Tagetes lucida, shows significant antimicrobial activity against WHO priority bacterial pathogens. This study evaluated the bactericidal effects of estragole, both in its chemically pure form and when isolated from the EOs of these plants, when used alone and in combination with the antibiotics meropenem and tobramycin against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria. Antibacterial activity was evaluated using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. The interaction of estragole with the selected antibiotics was analyzed using the checkerboard method, where the fractional inhibitory concentration index (FICI) was calculated. Results showed that estragole has inherent bactericidal properties, with MICs of no more than 256 μg/mL, indicating significant activity regardless of the bacteria's resistance profile. Combinations with meropenem and tobramycin exhibited pronounced synergy, achieving reductions in the MIC of up to 16-fold in over 88% of the bacteria tested. An additive or partially synergistic effect was evident in only around 11% of cases. These results highlight the potential of estragole as a therapeutic adjuvant capable of enhancing the efficacy of conventional antibiotics, reducing the required doses and the associated side effects and toxicities. Furthermore, this study emphasizes the beneficial potential of phytochemical-antibiotic combinations as an innovative strategy to address the growing threat posed by antimicrobial resistance.