Open AccessResistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniae
Author(s) -
Punyawee Dulyayangkul,
Edward Douglas,
Filip Lastovka,
Matthew B. Avison
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00409-20
Subject(s) - ceftazidime/avibactam , klebsiella pneumoniae , avibactam , microbiology and biotechnology , meropenem , ceftazidime , beta lactamase inhibitors , medicine , biology , antibiotic resistance , antibiotics , escherichia coli , pseudomonas aeruginosa , bacteria , genetics , gene
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.