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Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors.
Diagnostic Microbiology and Infectious Disease ( IF 2.9 ) Pub Date : 2020-07-25 , DOI: 10.1016/j.diagmicrobio.2020.115149
Andrea M Hujer 1 , S Wesley Long 2 , Randall J Olsen 2 , Magdalena A Taracila 1 , Laura J Rojas 1 , James M Musser 2 , Robert A Bonomo 3
Affiliation  

Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates. All blaNDM-1 (9/9) and the majority of blaNDM-1/OXA-48 (3/4) containing isolates were resistant to CAZ/AVI as predicted by WGS. The combination of ATM and CAZ/AVI restored susceptibility by disk diffusion assay. Unexpectedly, clinical Kp isolates bearing blaKPC-8 (V240G) and blaKPC-14 (G242 and T243 deletion) did not test fully resistant to CAZ/AVI. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Presumed phenotypes conferred by AMR determinants need to be tested if therapeutic decisions are being guided by their presence or absence.



中文翻译:

在肺炎克雷伯菌中使用全基因组测序预测 β-内酰胺耐药性:β-内酰胺酶抑制剂的挑战。

尽管多种抗菌素耐药性 (AMR) 决定因素可以赋予相同的体外抗菌药敏试验 (AST) 表型,但它们对最佳治疗选择的不同影响尚不确定。使用跨越 3.5 年的大量基于人群的临床菌株集合,我们应用 WGS 来检测抑制剂抗性 (IR)、超广谱 β-内酰胺酶 (ESBL) 和碳青霉烯抗性 (CR) β-内酰胺酶 ( bla )基因并将基因型与选定分离株中的 AST 表型进行比较。所有bla NDM-1 (9/9) 和大部分bla NDM-1/OXA-48WGS 预测,含有 (3/4) 的分离株对 CAZ/AVI 具有抗性。ATM 和 CAZ/AVI 的组合通过磁盘扩散试验恢复了敏感性。出乎意料的是,带有bla KPC-8 (V240G) 和bla KPC-14(G242 和 T243 缺失)的临床Kp分离株并未测试对 CAZ/AVI 具有完全抗性。最后,尽管 β-内酰胺酶背景复杂,CAZ/AVI 仍保持效力。如果治疗决策是由 AMR 决定因素赋予的假定表型,则需要对其进行测试。

更新日期:2020-08-25
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