Genomic analysis of carbapenemase-encoding plasmids and antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae 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 Klebsiella pneumoniae isolates causing human infections in Vietnam. The secondary objective was to investigate the prevalence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae in this setting. Our genomic analysis study characterized 105 of 245 clinical K. pneumoniae 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 bla TEM-1 (46.9%, 15/32). The genomic content of the bla NDM-4-harboring plasmids is highly variable. While bla OXA-181 and bla OXA-48 were predominantly located on an IncX3 and an IncL plasmid, respectively, the majority of plasmids harboring bla 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 K. pneumoniae ST23 strain, confirmed through both in vitro and in vivo experiments. Our study provides insights into plasmids harboring the carbapenemases New Delhi metallo-β-lactamase, oxacillinase-48 like, and K. pneumoniae carbapenemase-2 circulating in Vietnam.IMPORTANCECarbapenem resistance in Klebsiella pneumoniae 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.