Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.00797-17. Print 2017 Nov.
Carbapenem antibiotics are among the mainstays for treating infections caused by , especially in the Northwest United States, where carbapenem-resistant remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant occurred in 16 patients from five health care facilities in the state of Oregon. All isolates were defined as extensively drug resistant. Multilocus sequence typing revealed that the isolates belonged to sequence type 2 (international clone 2 [IC2]) and were >95% similar as determined by repetitive-sequence-based PCR analysis. Multiplex PCR revealed the presence of a carbapenemase gene, later identified as Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global phylogeny. Pacific Biosciences (PacBio) SMRT sequencing was also performed on one isolate to gain insight into the genetic location of the carbapenem resistance gene. We discovered that , flanked on either side by IS elements in opposite orientations, was carried on a 15,198-bp plasmid designated pORAB01-3 and was present in all 16 isolates. The plasmid also contained genes encoding a TonB-dependent receptor, septicolysin, a type IV secretory pathway (VirD4 component, TraG/TraD family) ATPase, an integrase, a RepB family plasmid DNA replication initiator protein, an alpha/beta hydrolase, and a BrnT/BrnA type II toxin-antitoxin system. This is the first reported outbreak in the northwestern United States associated with this carbapenemase. Particularly worrisome is that was carried on a plasmid and found in the most prominent worldwide clonal group IC2, potentially giving pORAB01-3 great capacity for future widespread dissemination.
碳青霉烯类抗生素是治疗 感染的主要药物之一,尤其是在美国西北部,那里的耐碳青霉烯类 仍然相对较少。然而,在 2012 年 6 月至 2014 年 10 月期间,俄勒冈州的五个医疗机构的 16 名患者发生了碳青霉烯类耐药 的爆发。所有分离株均被定义为广泛耐药。多位点序列分型显示,这些分离株属于序列型 2(国际克隆 2 [IC2]),通过重复序列基于 PCR 分析,它们的相似度>95%。多重 PCR 显示存在一种 碳青霉烯酶基因,随后被鉴定为 对所有分离株进行全基因组测序揭示了一个在全球 系统发育中具有良好支持的单独分支。还对一个分离株进行了太平洋生物科学公司(PacBio)SMRT 测序,以深入了解碳青霉烯类耐药基因的遗传位置。我们发现, 被两侧相反方向的 IS 元件包围,位于一个 15198bp 的质粒上,该质粒被命名为 pORAB01-3,存在于所有 16 个分离株中。该质粒还包含编码 TonB 依赖性受体、溶胞素、IV 型分泌途径(VirD4 成分、TraG/TraD 家族)ATP 酶、整合酶、RepB 家族质粒 DNA 复制起始蛋白、α/β水解酶和 BrnT/BrnA 型 II 毒素-抗毒素系统的基因。这是美国西北部首次报道的与这种碳青霉烯酶相关的爆发。特别令人担忧的是, 位于质粒上,并且存在于最突出的全球克隆群 IC2 中,这使得 pORAB01-3 具有未来广泛传播的巨大潜力。