Resistance to aztreonam in combination with non-β-lactam β-lactamase inhibitors due to the layering of mechanisms in Escherichia coli identified following mixed culture selection.
Cheung, C. H. P.; Dulyayangkul, P.; Heesom, K. J.; Avison, M.
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Using mixed culture selection, we show how reduced envelope permeability, reduced target-site affinity, and increased {beta}-lactamase production layer to confer aztreonam/{beta}-lactamase inhibitor resistance in Escherichia coli. We report a clinical isolate producing CTX-M-15 and CMY-4, lacking OmpF, and carrying a PBP3 mutation. It is resistant to aztreonam plus the inhibitors avibactam, relebactam and vaborbactam. Mobilisation of blaSHV-12 into this isolate generated a derivative additionally resistant to aztreonam plus the bicyclic boronate inhibitors 2 and taniborbactam.
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