Abstract
<title>Abstract</title> <p> <bold>Background:</bold> Pneumonia caused by <italic>Pseudomonas aeruginosa</italic> is increasingly difficult to treat due to Meropenem resistance, largely driven by the overexpression of the efflux pump MexAB-OprM, which expels the antibiotic from the bacterial cell before it reaches its target, allowing the pathogen to overcome Meropenem activity. Meropenem is crucial for managing multidrug-resistant (MDR) infections caused by <italic>Pseudomonas aeruginosa</italic> due to its broad-spectrum antibacterial activity. However, the emergence and accumulation of carbapenem-resistant mechanisms have elevated minimum inhibitory concentrations <italic>(</italic> MICs <italic>),</italic> significantly limiting therapeutic options. Among these resistance mechanisms, the overexpression of efflux pump systems is a major contributor. Notably, MexAB-OprM, the first efflux pump identified from the Resistance-Nodulation-Cell Division <italic>(</italic> RND <italic>)</italic> family, is constitutively expressed at high levels in <italic>P. aeruginosa</italic> , contributing substantially to both intrinsic and acquired resistance. Given their critical role as last-resort agents against increasingly difficult-to-treat Gram-negative pathogens, including <italic>P. aeruginosa</italic> , the prudent use of carbapenems is essential. <bold>Aim:</bold> The study aims to overcome efflux pump-mediated resistance in <italic>Pseudomonas aeruginosa</italic> through the synergistic effect of α-Bisabolol (a plant metabolite) and Meropenem (an antibiotic). <bold>Objective:</bold> To investigate the ability of the combination of Meropenem and the α-Bisabolol plant metabolite to resensitize the clinical Meropenem-resistant <italic>Pseudomonas aeruginosa</italic> by inhibiting the MexB efflux pump <italic>in vitro</italic> studies. <bold>Results:</bold> The combination of Meropenem and α-Bisabolol reduced the MIC of Meropenem by fourfold and significantly inhibited bacterial growth in time-kill assays. Ethidium bromide accumulation confirmed efflux inhibition, as evidenced by increased fluorescence in treated cells. These results suggest that α-Bisabolol effectively restores Meropenem activity and offers a promising strategy against resistant <italic>P. aeruginosa</italic> infections. </p>