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全球高危克隆株的引入是挪威产碳青霉烯酶菌株产生的主要驱动因素。

Import of global high-risk clones is the primary driver of carbapenemase-producing in Norway.

作者信息

Haldorsen Bjørg Christina, Samuelsen Ørjan, Janice Jessin, Sare Miriam, Molvik Mari, Sundsfjord Arnfinn, Pedersen Torunn

机构信息

Norwegian Centre for Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.

Department for Infection Control and Preparedness, Norwegian Institute of Public Health, Oslo, Norway.

出版信息

J Med Microbiol. 2025 Jan;74(1). doi: 10.1099/jmm.0.001944.

Abstract

Infections by carbapenemase-producing (CP-Pa) are concerning due to limited treatment options. The emergence of multidrug-resistant (MDR) high-risk clones is an essential driver in the global rise of CP-Pa. Insights into the molecular epidemiology of CP-Pa are crucial to understanding its clinical and public health impact. Despite the low incidence of infections in Norway, global spread requires an understanding of regional dissemination patterns. This study aimed to investigate the phenotypic and genotypic characteristics of CP-Pa isolates in Norway and molecular epidemiology by utilizing available metadata. The study collection comprised all verified CP-Pa isolated in Norway from 2006 to 2022 (=67) obtained from clinical (75%; =50) or screening samples (22%; =15) or had no available information (3%; =2). Phenotypic analyses included antimicrobial susceptibility testing against clinically relevant antipseudomonal antibiotics and comparative testing for carbapenemase production using three different methods (-CARBA, IMI/IMD gradient test and Coris O.K.N.V.I RESIST-5). Whole-genome sequencing was performed to identify virulence factors, resistance determinants and genomic relatedness. The isolates were categorized as MDR (=39) encoding Verona integron-encoded metallo--lactamase (VIM) (=28), New Delhi metallo--lactamase (NDM) (=6), imipenemase metallo--lactamase (IMP) (=4) or Guiana extended spectrum metallo--lactamase (=1) carbapenemases or extensively drug-resistant (XDR; 28) encoding VIM (=11), NDM (=9) or IMP (=8) carbapenemases. CP-Pa numbers ranged from 1 to 7 annually, peaking at 17 in 2022. Most isolates (=64) were associated with international travel or hospitalization abroad. Phylogenetic analyses identified nine clusters of closely related genomes, with one suspected case of domestic patient-to-patient transmission. Among 21 detected sequence types, several were global high-risk clones, including ST235 (=12), ST111 (=9), ST773 (=9), ST253 (=3), ST357 (=3), ST395 (=3), ST823 (=3), ST233 (=2), ST654 (=2), ST260 (=1) and ST308 (=1), covering 72% of the Norwegian isolates. ST1047 (IMP-1) and ST773 (NDM-1) were associated with Ukrainian war victims. Carbapenemase detection rates for phenotypic tests were 88% (-CARBA), 91% (IMI/IMD) and 94% (Coris) in our collection. The study highlights the low incidence yet high genomic diversity of CP-Pa in Norway and the dominance of high-risk clones linked to imports, contributing to the high proportion of XDR.

摘要

产碳青霉烯酶(CP-Pa)的感染令人担忧,因为治疗选择有限。多重耐药(MDR)高风险克隆的出现是全球CP-Pa感染增加的一个重要驱动因素。深入了解CP-Pa的分子流行病学对于理解其临床和公共卫生影响至关重要。尽管挪威的感染发病率较低,但全球传播需要了解区域传播模式。本研究旨在利用现有元数据调查挪威CP-Pa分离株的表型和基因型特征以及分子流行病学。研究收集了2006年至2022年在挪威分离出的所有经证实的CP-Pa(共67株),这些菌株来自临床样本(75%;共50株)或筛查样本(22%;共15株),或无可用信息(3%;共2株)。表型分析包括针对临床相关抗假单胞菌抗生素的药敏试验以及使用三种不同方法(-CARBA、IMI/IMD梯度试验和Coris O.K.N.V.I RESIST-5)进行碳青霉烯酶产生的比较试验。进行全基因组测序以鉴定毒力因子、耐药决定因素和基因组相关性。这些分离株被分类为编码维罗纳整合子编码金属β-内酰胺酶(VIM)(共28株)、新德里金属β-内酰胺酶(NDM)(共6株)、亚胺培南酶金属β-内酰胺酶(IMP)(共4株)或圭亚那超广谱金属β-内酰胺酶(共1株)碳青霉烯酶的MDR(共39株),或编码VIM(共11株)、NDM(共9株)或IMP(共8株)碳青霉烯酶的广泛耐药(XDR;共28株)。每年CP-Pa的数量在1至7株之间,2022年达到峰值17株。大多数分离株(共64株)与国际旅行或国外住院有关。系统发育分析确定了九个密切相关基因组的簇,其中有一例疑似国内患者间传播的病例。在检测到的21种序列类型中,有几种是全球高风险克隆,包括ST235(共12株)、ST111(共9株)、ST773(共9株)、ST253(共3株)、ST357(共3株)、ST395(共3株)、ST823(共3株)、ST233(共2株)、ST654(共2株)、ST260(共1株)和ST308(共1株),占挪威分离株的72%。ST1047(IMP-1)和ST773(NDM-1)与乌克兰战争受害者有关。我们收集的样本中,表型试验的碳青霉烯酶检测率分别为88%(-CARBA)、91%(IMI/IMD)和94%(Coris)。该研究突出了挪威CP-Pa感染发病率低但基因组多样性高的特点,以及与输入相关的高风险克隆的主导地位,这导致了XDR的高比例。

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