KPC-53, a KPC-3 Variant of Clinical Origin Associated with Reduced Susceptibility to Ceftazidime-Avibactam

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Klebsiella pneumoniae is a significant opportunistic pathogen.
• Ceftazidime-avibactam is a crucial antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria.
• Emergence of resistance to ceftazidime-avibactam poses a serious threat to public health.

Purpose of the Study:

• To characterize a Klebsiella pneumoniae clinical isolate with high-level resistance to ceftazidime-avibactam.
• To identify the genetic basis of this resistance.
• To understand the mechanisms underlying ceftazidime-avibactam resistance.

Main Methods:

• Phenotypic characterization of antibiotic resistance.
• Whole-genome sequencing (WGS) to identify genetic determinants.
• Plasmid analysis to determine gene location.

Main Results:

• Identification of a Klebsiella pneumoniae isolate with high-level ceftazidime-avibactam resistance.
• Characterization of KPC-53, a novel KPC-3 variant with a Leu167Glu168 duplication in the Ω-loop and loss of carbapenemase activity.
• Detection of two copies of the blaKPC-53 gene: one on a pKpQIL-like plasmid and another on a Siphoviridae family plasmid prophage.

Conclusions:

• The study elucidates a novel mechanism of ceftazidime-avibactam resistance in Klebsiella pneumoniae.
• The KPC-53 enzyme variant and its unique genetic location contribute to high-level resistance.
• Findings provide critical insights into the evolving landscape of antibiotic resistance.