Increased antimicrobial resistance requires effective ways to overcome the global challenge of bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). From the emergence of MRSA to its continued evolution, it is important to explore this pathogen from fresh perspectives and develop corresponding coping strategies to counter its growing threat. New coping strategies are continuously emerging, including but not limited to enhancing penetration capabilities or targeting their virulence. This review summarizes the epidemiological characteristics, drug resistance mechanisms, and therapeutic strategies of MRSA that have emerged over the past fifteen years. The focus of this paper is to explore the promising applications and current limitations of novel MRSA control strategies. This review serves as a key resource for treating MRSA infections and discussing novel strategies to overcome bacterial drug resistance.

Rutin is a widely known plant secondary metabolite that exhibits multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing rutin, and further explored the mechanisms behind this synergy. In vitro antibacterial test results of rutin showed that the ranges of minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) are 0.125–1 and 0.125–2 mg/mL, respectively. However, rutin and amikacin have a significant synergistic effect, with a fractional inhibitory concentration index (FICI) range of 0.1875–0.5. The time bactericidal curve proved that the combination of rutin and amikacin inhibited bacterial growth within 8 h. Scanning electron microscopy (SEM) revealed that a low-dose combination treatment could disrupt the cell membrane of Escherichia coli (E. coli). A comprehensive analysis using alkaline phosphatase (AKP), K⁺, and a protein leakage assay revealed that co-treatment destroyed the cell membrane of E. coli, resulting in the significant leakage of AKP, intracellular K⁺, and proteins. Moreover, confocal laser scanning microscopy (CLSM) and red–green cell ratio analysis indicated severe damage to the E. coli cell membrane following the co-treatment of rutin and amikacin. This study indicates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect, which could significantly control antibiotic resistance.