Antimicrobial resistance mechanisms, treatment challenges, and emerging strategies in Stenotrophomonas maltophilia infections.

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen widely distributed in natural and clinical environments, and has increasingly been recognized as a significant cause of nosocomial infections. Owing to its complex intrinsic resistance mechanisms and the continuous evolution of acquired resistance, the clinical management of S. maltophilia infections remains highly challenging. Resistance in S. maltophilia is mediated by multiple mechanisms, including chromosomally encoded L1/L2 β-lactamases, multidrug efflux pump systems, reduced outer membrane permeability, and biofilm formation, as well as the acquisition of resistance determinants via mobile genetic elements. In addition, virulence-associated traits, including quorum sensing systems, and extracellular enzyme production, contribute to host adaptation and persistent infection. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first-line therapy. However, increasing resistance has been reported in certain regions. Alternative and combination therapies, including minocycline and fluoroquinolones, are increasingly utilized. Meanwhile, emerging strategies such as efflux pump inhibitors, anti-virulence approaches, and bacteriophage therapy have attracted growing attention. This review provides a comprehensive overview of the resistance mechanisms, virulence-associated phenotypes, and current therapeutic advances of S. maltophilia, with particular emphasis on resistance evolution and novel treatment strategies. These insights may advance our understanding of host-pathogen interactions and support the development of targeted therapeutic approaches for improved clinical management.