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  • 标题:Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks
  • 本地全文:下载
  • 作者:Gustavo C. Cerqueira ; Ashlee M. Earl ; Christoph M. Ernst
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2017
  • 卷号:114
  • 期号:5
  • 页码:1135-1140
  • DOI:10.1073/pnas.1616248114
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae . There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC ( K. pneumoniae carbapenemases) beta-lactamases encoded by bla KPC2, bla KPC3, and bla KPC4, which were transferred between strains and species by seven distinct subgroups of the Tn 4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.
  • 关键词:carbapenem resistance ; Enterobacteriaceae ; comparative genomics ; whole-genome sequencing ; molecular evolution
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