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Resistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniae.
Antimicrobial Agents and Chemotherapy ( IF 4.1 ) Pub Date : 2020-09-21 , DOI: 10.1128/aac.00409-20
Punyawee Dulyayangkul 1 , Edward J A Douglas 1 , Filip Lastovka 1 , Matthew B Avison 2
Affiliation  

Serine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae isolates. Recently, this has driven clinical deployment of the β-lactam–β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps, i.e., ompK36 and ramR mutation plus carriage of OXA-232 and KPC-3-D178Y variant β-lactamases, confer ceftazidime/avibactam and meropenem/vaborbactam resistance when both pairs are used together. These findings have implications for decision making about sequential and combinatorial use of these β-lactam–β-lactamase inhibitor pairs to treat K. pneumoniae infections.

中文翻译:

在金属β-内酰胺酶阴性肺炎克雷伯菌的四个步骤中实现了对头孢他啶/阿维巴坦+美罗培南/ Vaborbactam的抗药性。

丝氨酸β-内酰胺酶是肺炎克雷伯菌分离株中β-内酰胺抗性的主要原因。最近,这推动了β-内酰胺-β-内酰胺酶抑制剂对头孢他啶/阿维巴坦和美罗培南/ vaborbactam的临床应用。我们显示了四个步骤,即ompK36ramR突变加上OXA-232和KPC-3-D178Y变异β-内酰胺酶的运输,当将两对一起使用时,赋予头孢他啶/ avibactam和美洛培南/ vaborbactam耐药。这些发现对于顺序和联合使用这些β-内酰胺-β-内酰胺酶抑制剂对治疗肺炎克雷伯菌感染具有决定意义。
更新日期:2020-09-21
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