Resistance to Ceftazidime/Avibactam Plus Meropenem/Vaborbactam When Both are Used Together Achieved in Four Steps from Metallo-β-Lactamase Negative <i>Klebsiella pneumoniae</i>.

Punyawee Dulyayangkul, Edward J. A. Douglas, Filip Lsstovka, Matthew B Avison*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Serine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae. Recently, this has driven clinical deployment of the β-lactam/β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps: 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.
Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Early online date13 Jul 2020
DOIs
Publication statusE-pub ahead of print - 13 Jul 2020

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