KPC-39-mediated resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 clinical isolate

Antimicrob Agents Chemother. 2021 Oct 4:AAC0116021. doi: 10.1128/AAC.01160-21. Online ahead of print.

ABSTRACT

Resistance to ceftazidime-avibactam (CAZ-AVI) combination is being increasingly reported. Here, we report a CAZ-AVI resistant Klebsiella pneumoniae belonging to the high-risk ST307 clone and producing KPC-39, a single amino-acid variant of KPC-3 (A172T). Cloning experiments, steady state kinetic parameters and molecular dynamics simulations revealed a loss of carbapenemase activity and an increased affinity for ceftazidime. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European healthcare settings.

PMID:34606331 | DOI:10.1128/AAC.01160-21