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

在低收入和中等收入国家，革兰氏阴性菌对碳青霉烯类药物的耐药性正在上升。我们开展了一项单中心研究，以鉴定在越南导致人类感染的耐碳青霉烯类分离株中携带碳青霉烯酶的质粒。次要目标是调查在这种情况下多重耐药（MDR）和高毒力菌株的流行情况。我们的基因组分析研究对越南河内第108军事医院在2021年1月1日至2021年12月31日期间从重症监护病房和普通病房收集的245株临床分离株中的105株进行了特征分析。所有分离株均使用长读长和短读长测序进行特征分析，随后进行混合组装。进行了全面的基因组分析以鉴定携带碳青霉烯酶的质粒，并通过对常用和新型抗生素进行扩展抗生素敏感性测试加以补充。我们观察到与NDM-4相关的碳青霉烯类耐药性的高流行率（30.5%，32/105），主要由一种特定的83 kb IncFII质粒携带，该质粒还共携带 blaCTX-M-15（46.9%，15/32）。携带 blaCTX-M-15的质粒的基因组内容高度可变。虽然 blaTEM-1B和 blaSHV-12分别主要位于IncX3和IncL质粒上，但大多数携带 blaCTX-M-15的质粒与任何已命名的Inc类型均无关。所有分离株均表现出MDR表型；然而，大多数分离株对铁载体头孢菌素头孢地尔仍敏感（79%，83/105）。所有分离株对氨曲南/阿维巴坦均敏感。此外，我们鉴定出一株高毒力、耐碳青霉烯类的ST23菌株，通过小鼠致死率和组织病理学实验得以证实。我们的研究深入了解了在越南传播的携带碳青霉烯酶新德里金属β-内酰胺酶、类奥克西林酶-48和KPC碳青霉烯酶-2的质粒。

重要性

革兰氏阴性菌对碳青霉烯类药物的耐药性是一项重大的公共卫生威胁，尤其是在低收入和中等收入国家。本研究检查了来自越南一家医院的耐药菌株，以了解它们如何传播以及哪些抗生素可能仍然有效。我们发现，这些细菌中有相当数量在不同类型的质粒上携带耐药基因。尽管它们对许多抗生素耐药，但大多数菌株对头孢地尔和氨曲南/阿维巴坦等新型药物仍敏感。令人担忧的是，我们还鉴定出一株耐碳青霉烯类的高毒力菌株，这可能对患者构成更大风险。本研究深入了解了越南一家医院中携带碳青霉烯酶基因的质粒的流行病学情况。了解这些耐药模式有助于指导抗生素的使用和政策决策，以应对越南多重耐药感染日益增长的威胁。