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基因组学洞察控制万古霉素耐药肠球菌的出现。

Genomic insights to control the emergence of vancomycin-resistant enterococci.

机构信息

Austin Centre for Infection Research (ACIR), Infectious Diseases Department, Austin Health, Heidelberg, Victoria, Australia.

出版信息

mBio. 2013 Aug 13;4(4):e00412-13. doi: 10.1128/mBio.00412-13.

DOI:10.1128/mBio.00412-13
PMID:23943759
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3747580/
Abstract

UNLABELLED

Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm.

IMPORTANCE

Enterococcus faecium is an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in hospitals globally, yet in many institutions around the world, vancomycin-resistant E. faecium (VREfm) infections continue to rise. The new findings from this study help explain the failures of our current approaches to controlling vanB VREfm in health care institutions. Given the importance of this bacterium as a cause of hospital-acquired infections and the difficulties faced by infection control units in trying to prevent colonization in their institutions, the novel findings from this study provide evidence that a new approach to controlling VREfm in hospitals is required. In particular, more attention should be given to understanding the epidemiology of hospital-adapted vancomycin-susceptible E. faecium, and patients at higher risk for de novo generation of VREfm need to be identified and optimally managed.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/6a5ae1d21e2c/mbo0041315890006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/d0cd6bef37dc/mbo0041315890001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/f6d0293d7088/mbo0041315890002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/a52f36f8ec79/mbo0041315890003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/b20946e82c9d/mbo0041315890004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/13ac023a2421/mbo0041315890005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/6a5ae1d21e2c/mbo0041315890006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/d0cd6bef37dc/mbo0041315890001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/f6d0293d7088/mbo0041315890002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/a52f36f8ec79/mbo0041315890003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/b20946e82c9d/mbo0041315890004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/13ac023a2421/mbo0041315890005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/3747580/6a5ae1d21e2c/mbo0041315890006.jpg

目的

万古霉素耐药粪肠球菌(VREfm)医院感染暴发被认为是通过患者之间 VREfm 的传播而发生的,这表明感染控制策略将限制交叉传播。尽管实施了这些策略,VREfm 感染的发病率仍在继续上升。我们旨在利用基因组学更好地了解大型医院内粪肠球菌的流行病学,并探讨感染控制策略失败的原因。对 61 株粪肠球菌(36 株 VREfm)分离株进行了全基因组测序,这些分离株主要来自 1998 年至 2009 年期间在一家医院采集的血培养物,对从人类粪便中分离出的 5 株 vanB 阳性厌氧共生菌进行了测序。基于全基因组的系统发育分析和精确绘制 vanB 基因图谱,结果表明,36 株 VREfm 分离株中至少有 18 株是通过独立的插入事件获得转座子的,这表明 VREfm 是新生成的,而不是交叉传播的。此外,在 36 株 VREfm 分离株中的 15 株中发现的 Tn1549 序列与其中一株肠道厌氧菌中的 Tn1549 序列相同。来自国家和国际比较的粪肠球菌分离株与我们医院的分离株在系统发育上相互穿插,这表明我们的发现可能具有全球代表性。这些数据表明,患者体内 VREfm 的产生很常见,可能发生在抗生素治疗期间的人类肠道中,这有助于解释我们无法降低 VREfm 感染的原因。我们的研究结果表明,感染控制措施应包括筛查患者是否携带特定的医院克隆万古霉素敏感粪肠球菌,而不仅仅是 VREfm。

意义

粪肠球菌是一种日益重要的人类病原体,主要引起住院患者的抗生素耐药性感染。全球大量的医疗保健资金用于试图控制医院内的抗生素耐药细菌,但在世界各地的许多机构中,万古霉素耐药粪肠球菌(VREfm)感染仍在继续上升。这项研究的新发现有助于解释我们目前控制医疗机构中 vanB VREfm 的方法的失败。鉴于该细菌作为医院获得性感染的原因的重要性以及感染控制单位在试图防止其机构内定植方面所面临的困难,这项研究的新发现提供了证据,表明需要采取新的方法来控制医院内的 VREfm。特别是,应更加重视了解医院适应的万古霉素敏感粪肠球菌的流行病学,需要识别和最佳管理易发生 VREfm 新生成的高风险患者。

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