Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types.
Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types.
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DOI：
10.1099/mgen.0.000789
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发表时间：
2022-04
影响因子：
3.9
通讯作者：
Hubbard, Alasdair T. M.
中科院分区：
文献类型：
--
作者：
Edwards, Thomas;Heinz, Eva;van Aartsen, Jon;Howard, Alex;Roberts, Paul;Corless, Caroline;Fraser, Alice J.;Williams, Christopher T.;Bulgasim, Issra;Cuevas, Luis E.;Parry, Christopher M.;Roberts, Adam P.;Adams, Emily R.;Mason, Jenifer;Hubbard, Alasdair T. M.
哌拉西林/他唑巴坦（TZP）耐药 大肠杆菌 主要与对第三代头孢菌素产生耐药性的机制有关。最近的报告指出， E.杆菌 对哌拉西林/他唑巴坦表型耐药，但对第三代头孢菌素（TZP-R/3GC-S）敏感的菌株。在这项研究中，我们试图确定这种表型的遗传多样性， E.杆菌 （n=58）2014-2017年在英国利物浦的一家三级医院分离的，以及相关的耐药机制。我们将我们的发现与英国范围内的侵入性 E.杆菌 具有公开表型和基因型数据的分离株（n=1509）。这些数据集包括TZP-R/3GC-S表型（n=68），哌拉西林/他唑巴坦和第三代头孢菌素敏感（TZP-S/3GC-S，n=1271）表型。TZP-R/3GC-S表型显示在广泛的序列类型中，这反映在来自英国范围收集的相同表型中，并且侵袭性肿瘤的总体多样性在不同的序列类型中是不同的。 E.杆菌 分离株TZP-R/3GC-S分离株含有多种质粒，表明TZP抗性机制的多个获得事件，而不是特定质粒或序列类型的克隆扩增。假定的耐药机制同样多样，包括TEM-1的过度产生，通过强启动子或基因扩增，携带耐药β-内酰胺酶，以及首次在临床分离株中检测到的S133 G bla CTX-M-15突变。这些机制中的几种在来自英国范围收集的TZP-S/3GC-S分离株中以较低的丰度存在，但没有对TZP的相关表型抗性。11株（19%）的分离株没有从基因组数据中确定的推定机制。我们的研究结果强调了这种隐蔽表型的复杂性，需要持续的表型监测，以及进一步的研究，以改善从基因组数据中检测和预测TZP-R/3GC-S表型。
Resistance to piperacillin/tazobactam (TZP) in Escherichia coli has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified E. coli strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in E. coli (n=58) isolated between 2014–2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive E. coli isolates (n=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, n=1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive E. coli isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G bla CTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.
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