Evaluating the Antimicrobial Activity of Esomeprazole Magnesium Trihydrate on Antibiotic-Resistant Bacteria Using Efflux Pumps

Abstract

BACKGROUND: Antibiotic resistance mediated by efflux pumps is a serious public health threat. Esomeprazole magnesium trihydrate (EMT) is a proton pump inhibitor with reported antimicrobial activity, but its effects against efflux-mediated resistance are unknown. OBJECTIVE: To evaluate the antimicrobial activity of EMT alone and in combination with the efflux pump inhibitor reserpine against clinical isolates of _Pseudomonas aeruginosa, Acinetobacter baumannii_ and _Staphylococcus aureus_. METHODS: Minimum inhibitory concentration (MIC) assays were performed using the broth microdilution method on 15 non-duplicate clinical isolates and reference strains with/without EMT and reserpine. RESULTS: EMT demonstrated activity against all isolates, with MIC ranges of 4-32 μg/mL, 8-64 μg/mL and 2-16 μg/mL respectively. EMT MICs decreased 4-8-fold for 13/15 isolates when combined with reserpine, indicating EMT may inhibit efflux pumps. Similar reductions occurred for comparator antibiotics. CONCLUSIONS: This study provides the first evidence that EMT possesses intrinsic antimicrobial activity against these pathogens and may function as both an efflux pump substrate and inhibitor. EMT warrants further investigation as a potential adjuvant antibiotic for overcoming efflux-mediated resistance.