Dehydrocostus lactone from Echinops kebericho Mesfin synergizes the antibacterial effects of gentamicin and ciprofloxacin

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Abstract Background: Combination therapy is becoming an appealing solution to the emergence of antimicrobial resistance (AMR). This study investigated the combinatory effects of dehydrocostus lactone (DCL) and essential oil (EO) from Echinops kebericho when combined with selected standard antibacterial antibiotics. Methods: The minimum inhibitory concentration (MIC) was determined using broth microdilution. Checkerboard analyses were used to determine the interactive effect. Eight serials, two-fold dilutions of conventional antibiotics and DCL/EO were prepared by diluting in broth. Dilutions of 50μl of antibiotic were dispensed in rows; while those of the EO/ DCL were dispensed in columns (1:1 v/v) of different concentrations ranging from 1/32 × MIC to 4 × MIC. In isobole analysis the EO/ DCL were combined with conventional antibiotics in nine different ratios. Isobolograms of the combination of DCL/EO with antibiotics were constructed. Results:Out of a total of 90 different combinations evaluated, only five (5.55%) showed a synergistic effect; the majority (80%) showed no interaction, while 14.44% showed an additive effect. No antagonistic effect was observed in all combinations tested. Beta-lactam antibiotics were non-interactive range of ΣFIC with DCL with the exception of a 3:7 DCL to penicillin combination with ∑FIC =1, in the additive range. All combinations of EO with selected beta-lactam antibiotics were in the non-interactive range. In this study, isobole analyses have shown the dependence of interactive effects on the ratio of combining agents. The DCL combination ratios of gentamicin or ciprofloxacin showed a synergistic effect. Conclusion: Dehydrocostus lactone showed a synergistic effect against methicillin resistant Staphylococcus aureus (MRSA) when combined with ciprofloxacin or gentamicin. The observed synergistic effect could be useful for combating resistant strains. Further investigations are required on the mechanism of synergism and reversing resistance.

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