Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain

Abstract

This study describes KPC-204, a novel variant of Klebsiella pneumoniae carbapenemase, characterized by a Lys-Asp-Asp (KDD) amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204’s contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Docking simulations revealed a weaker interaction between KPC-204 and avibactam compared to KPC-2. Mating experiments demonstrated the resistance’s transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.