Confronting blaNDM-5 in Salmonella Typhi: From Molecular Epidemiology, Resistance Mechanism to Clinical Management

Abstract: The emergence of Carbapenem-Resistant Salmonella enterica serovar Typhi (CR Salmonella enterica var typhi ) represents a critical challenge in the prevention and control of typhoid fever. In recent years, CR Salmonella enterica var typhi strains carrying the bla NDM-5 gene have rapidly disseminated worldwide, particularly across South Asia such as India and Pakistan, severely exacerbating the clinical treatment failure rates and significant mortality. Due to the acceleration of global travel and trade, the multidrug resistant clones mainly transmitted through plasmids (such as lncX3), increasingly endanger China with historically low resistance levels. The CR Salmonella enterica var typhi strains exhibit extensive resistance to fluoroquinolones, cephalosporins, and carbapenems, compromising the effectiveness of conventional treatment regimens. Herein, efforts are made to provide a comprehensive review on the global epidemiology, underlying resistance mechanisms, the evolving challenges in clinical management. The antimicrobial resistance surveillance systems, such as whole-genome sequencing (WGS) technology, strict antibiotic management, infection control measures, and future perspectives on the combination therapies (such as meropenem combined with polymyxin) have also been discussed and outlooked. It is highly anticipated that the surveillance technologies combined with potential therapeutic pathways will witness a leap-forward development in clinical translation for public health. Keywords: Salmonella enterica , carbapenem resistance, bla NDM-5 global dissemination