Genomic analysis of carbapenemase-encoding plasmids and antibiotic resistance in carbapenem-resistant <i>Klebsiella pneumoniae</i> isolates from Vietnam, 2021

Carbapenem resistance in gram-negative rods is increasing in low- and middle-income countries. We conducted a single-center study to identify carbapenemase-encoding plasmids in carbapenem-resistant <i>Klebsiella pneumoniae</i> isolates causing human infections in Vietnam. The secondary objective was to investigate the prevalence of multidrug-resistant (MDR) and hypervirulent <i>K. pneumoniae</i> in this setting. Our genomic analysis study characterized 105 of 245 clinical <i>K. pneumoniae</i> isolates at the 108 Military Hospital in Hanoi, Vietnam, collected from intensive care unit and regular wards between 1 January 2021 and 31 December 2021. All isolates were characterized using long- and short-read sequencing, followed by hybrid assembly. Comprehensive genomic analysis was performed to identify carbapenemase-encoding plasmids, complemented by extended antibiotic susceptibility testing for commonly used and novel antibiotics. We observed a high prevalence of NDM-4-related carbapenem resistance (30.5%, 32/105) mostly carried by a specific 83-kb IncFII plasmid co-carrying the <i>bla</i> _TEM-1 (46.9%, 15/32). The genomic content of the <i>bla</i> _NDM-4-harboring plasmids is highly variable. While <i>bla</i> _OXA-181 and <i>bla</i> _OXA-48 were predominantly located on an IncX3 and an IncL plasmid, respectively, the majority of plasmids harboring <i>bla</i> _KPC-2 were not related to any named Inc-type. All isolates exhibited the MDR phenotype; however, the majority remained susceptible to the siderophore-cephalosporin cefiderocol (79%, 83/105). All isolates were susceptible to aztreonam/avibactam. In addition, we identified a hypervirulent, carbapenem-resistant <i>K. pneumoniae</i> ST23 strain, confirmed through both <i>in vitro</i> and <i>in vivo</i> experiments. Our study provides insights into plasmids harboring the carbapenemases New Delhi metallo-β-lactamase, oxacillinase-48 like, and <i>K. pneumoniae</i> carbapenemase-2 circulating in Vietnam.IMPORTANCECarbapenem resistance in <i>Klebsiella pneumoniae</i> is a major public health threat, especially in low- and middle-income countries. This study examined resistant strains from a hospital in Vietnam to understand how they spread and which antibiotics might still work. We found that a significant number of these bacteria carried resistance genes on different types of plasmids. Despite their resistance to many antibiotics, most strains remained susceptible to newer substances like cefiderocol and aztreonam/avibactam. Alarmingly, we also identified a hypervirulent strain that is carbapenem resistant, potentially posing an even greater risk to patients. This research provides insight into the epidemiology of the carbapenemase gene-harboring plasmids in a Vietnamese hospital. Understanding these resistance patterns can help guide antibiotic use and policy decisions to combat the growing threat of multidrug-resistant infections in Vietnam.