Abstract
BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) pose a critical global threat. However, the genomic epidemiology, transmission dynamics (clonal vs. horizontal gene transfer), and mechanisms driving co-resistance in Southern Vietnam remain poorly understood. This study aimed to use Whole-Genome Sequencing (WGS) to characterize the molecular epidemiology, transmission mechanisms, and co-resistance patterns of CRE from a major referral center in Southern Vietnam. METHODOLOGY: We performed a cross-sectional study using whole-genome sequencing on 189 CRE isolates (K. pneumoniae, E. coli, E. cloacae) from a major referral hospital in Southern Vietnam. We analyzed Carbapenemase-Producing Genes (CPGs), MLST, colistin resistance mutations, plasmid clusters, and co-carried AMR genes. RESULTS: K. pneumoniae ST16 (n=67, 35.4%) was the most frequently identified clone, detected in 10/12 ward strata. We identified two distinct colistin resistance pathways linked to CPG lineage: bla (KPC)/bla (OXA-48) family clones (ST147, ST5815, ST11) showed a universal prevalence of chromosomal pmrB mutations (n=55/55, 100%), whereas the bla (NDM) clone (ST16) exhibited a low frequency of these mutations (6.0%). Analysis of 10 plasmid clusters carrying CPGs revealed the frequent co-carriage of qnrS1 (quinolone resistance) and rmtB1 (amikacin resistance). CONCLUSIONS: CRE dissemination in Southern Vietnam is driven by a dual-transmission scenario. We identified distinct CPG-linked colistin resistance pathways and significant co-carriage of qnrS1 with CPGs. This highlights the potential risk of co-selection through antibiotic pressure. These findings underscore the urgent need for surveillance strategies targeting high-risk clones like K. pneumoniae ST16.