Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses
Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses
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DOI：
10.1093/cid/ciw691
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发表时间：
2017-01-15
影响因子：
11.8
通讯作者：
Litvintseva, Anastasia P.
中科院分区：
文献类型：
--
作者：
Lockhart, Shawn R.;Etienne, Kizee A.;Litvintseva, Anastasia P.
背景耳念珠菌是一种引起侵袭性感染的多药耐药酵母菌，于2009年在日本首次报道，此后已有多个国家报道。为了了解C. auris分离到54例患者的C. 2012-2015年期间来自巴基斯坦、印度、南非和委内瑞拉的auris感染和来自日本的模式标本。41株分离株的患者信息可用。我们进行了抗真菌药敏试验和全基因组测序（WGS）。现有的临床资料显示，41%的患者患有糖尿病，51%的患者最近接受过手术，73%的患者有中心静脉导管，41%的患者在C.耳道分离。从入院到感染的中位时间为19天（四分位距，9-36天），61%的患者发生血液感染，59%死亡。使用严格折点，93%的分离株耐氟康唑，35%的抗真菌素B，7%的棘白菌素; 41%的耐2类抗真菌药和4%的耐3类。WGS表明，分离物按地理区域分为独特的分支。进化枝由数千个单核苷酸多态性分开，但在每个进化枝内，分离物是克隆的。ERG 11的不同突变与各地理分支的唑类耐药相关。C.耳炎是一种新出现的与保健相关的病原体，死亡率很高。由于抗真菌药物耐药性，治疗选择有限。WGS分析表明，几乎同时，最近，独立出现的不同克隆种群在3大洲。需要阐明风险因素和传播机制，以指导控制措施。
Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries.Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS).Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade.Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.