Fluoroquinolone Resistance in Salmonella: Deciphering Molecular Mechanisms, Global Dissemination Dynamics, and Clinical Countermeasures

Increasing clinical use of fluoroquinolone antibiotics has led to a rapid surge in fluoroquinolone-resistant Salmonella strains, markedly constraining the therapeutic armamentarium and increasing treatment failure risks. Epidemiological surveillance reveals high prevalence rates of resistant isolates across Asia, Africa, Europe, and the Americas, with infection-associated mortality remaining persistently elevated—a situation that poses a formidable threat to global public health. Despite this urgency, systematic investigations elucidating the precise molecular underpinnings of resistance and the mechanistic pathways governing transnational dissemination remain insufficient. This comprehensive review delineates the resistance and propagation mechanisms of fluoroquinolone-resistant Salmonella, with particular emphasis on the synergistic interplay between chromosomal mutations in gyrA/parC and the overexpression of efflux pump systems, alongside the horizontal transfer of plasmid-mediated quinolone resistance (PMQR) determinants—including qnr, aac(6′)-Ib-cr, and oqxAB—facilitated by integrons, transposons, and insertion sequences (ISs). The intricate complexity of these resistance mechanisms and dissemination routes poses substantial challenges to clinical therapeutics, rendering conventional antibiotic regimens progressively ineffective. Accordingly, this review further explores the development of novel therapeutic modalities and antimicrobial agents, aiming to inform evidence-based prevention and control strategies.