Impaired inhibition by avibactam and resistance to the ceftazidime-avibactam combination due to the D(179)Y substitution in the β-lactamase KPC-2.

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Impaired inhibition by avibactam and resistance to the ceftazidime-avibactam combination due to the D(179)Y substitution in the β-lactamase KPC-2.

Antimicrob Agents Chemother. 2017 May 01;:

Authors: Compain F, Arthur M

Abstract
The ceftazidime-avibactam combination was recently shown to be at risk of emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a KPC-2 β-lactamase harboring the D(179)Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for resistance. In contrast, the D(179)Y substitution abolished hydrolysis of aztreonam and imipenem indicating these drugs might provide therapeutic alternatives.

PMID: 28461318 [PubMed - as supplied by publisher]