Statistical analysis -normality of input data.

<div><p>Antimicrobial resistance is increasing globally and is one of the major public health concerns. This highlights the need to search for new antimicrobial agents. Natural fruit by-products are a rich source of bioactive compounds. Pomegranate (<i>Punica granatum</i>) fruit is particularly rich in phenolic bioactive phytochemicals. These compounds are known for their antioxidant, anti-inflammatory, and anticancer properties. Furthermore, they exhibit a broad spectrum of antimicrobial effects. Bioactive phytochemicals are found mainly in peel (exocarp and mesocarp), which constitutes about 50% of the whole fresh fruit. This study utilized pomegranate of Jordanian origin to evaluate the antimicrobial activity of different Pomegranate peel extracts (PPEs) alone and/or in combination with antibacterial agents against four bacterial strains. Different solvents and extraction methods were employed to obtain the PPEs. A key focus was to explore the enhancement of antibacterial activity against gentamicin-resistant <i>Pseudomonas aeruginosa</i> (<i>P</i>. <i>aeruginosa</i>) when microwaved aqueous extracts are combined with gentamicin. The antibacterial activity of PPEs varied depending on the extraction method and the solvent used. Notably, the aqueous macerate and microwave-assisted extract showed high potency and similar activity against <i>Staphylococcus aureus</i> (<i>S</i>. <i>aureus</i>), <i>Escherichia coli (E</i>. <i>coli)</i>, and <i>P</i>. <i>aeruginosa</i> (MICs 12.5, 25, and 25 μg/μL, respectively for both aqueous extracts). In contrast, <i>Proteus mirabilis</i> (<i>P</i>. <i>mirabilis</i>) was more susceptible to the inhibitory activity of organic PPEs with a MIC of 25 μg/μL recorded with the use of ethanolic solvents. Bacterial antagonistic activity was observed against gentamicin-resistant <i>P</i>. <i>aeruginosa</i>, particularly when lower concentrations (3.125, 1.562, 0.781, and 0.39 μg/μL) of microwaved aqueous PPEs were evaluated in combination with different concentrations of gentamicin. In conclusion, pomegranate peels, a natural and safe by-product, demonstrate promising antimicrobial potential. Furthermore, combining PPEs with conventional antibiotics shows promise in addressing antibiotic resistance, highlighting their potential role in treating infectious diseases.</p></div>