Molecular Characterization of Pandrug-, Extensively Drug-, and Multidrug-Resistant <i>Stenotrophomonas maltophilia</i> Isolates from Thailand

<i>Stenotrophomonas maltophilia</i> is a Gram-negative opportunistic pathogen associated with severe hospital-acquired infections. The multiple drug-resistant nature of <i>S. maltophilia</i> poses significant challenges in treating infections caused by it. In this study, genomic, antimicrobial susceptibility, and virulence phenotypic analyses of four <i>S. maltophilia</i> clinical isolates-strains SMC1291, SMC3920, SMC5345, and SMC5580-were conducted. Comparative genome analysis of these strains against publicly available clinical and environmental isolates revealed its relativeness and key antimicrobial resistance mechanisms. A phylogenetic tree revealed that <i>S. maltophilia</i> SMC5345 is closely related to SMC3920, whereas SMC5580 is closely related to <i>Stenotrophomonas sepilia</i>-the <i>S. maltophilia</i> complex. SMC1291 exhibited resistance to trimethoprim-sulfamethoxazole and gentamicin due to the acquisition of the antibiotic resistance genes <i>sul1</i> and <i>aac(6')-Ib</i>, resulting in an extensively drug-resistant strain. SMC3920 showed resistance to trimethoprim-sulfamethoxazole and quaternary ammonium compounds, arising from the acquisition of antimicrobial resistance genes <i>sul1</i> and <i>qacF</i>. SMC3920 also demonstrated resistance to levofloxacin and minocycline, which was attributed to the L116Q amino acid substitution in SmeT. The combined acquisition of antimicrobial resistance genes and a chromosomal mutation rendered strain SMC3920 resistant to all clinically relevant antibiotics, classifying it as a pandrug-resistant (PDR) strain. Notably, <i>sul1</i>, <i>aac(6')-Ib</i>, and <i>qacF</i> were encoded within the mobile genetic element class 1 integron. The effects of <i>sul1</i> and <i>qacF</i> upon gene transfer were studied, corroborating their contribution to the antimicrobial resistance phenotype. Even though the PDR strain SMC3920 remained susceptible to aztreonam and ceftazidime/avibactam combination, exploration of novel therapeutic strategies is urgently needed to combat these difficult-to-treat <i>S. maltophilia</i> infections.