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Review
. 2023 Dec 20;36(4):e0000823.
doi: 10.1128/cmr.00008-23. Epub 2023 Nov 8.

Klebsiella pneumoniae carbapenemase variants: the new threat to global public health

Li Ding #  1   2 , Siquan Shen #  1   2 , Jing Chen  3 , Zhen Tian  3 , Qingyu Shi  1   2 , Renru Han  1   2 , Yan Guo  1   2 , Fupin Hu  1   2
Affiliations
Review

Klebsiella pneumoniae carbapenemase variants: the new threat to global public health

Li Ding et al. Clin Microbiol Rev. .

Abstract

Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild blaKPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 blaKPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting blaKPC variants, treatment options, and future perspectives of blaKPC variants worldwide to alert this new great public health threat.

Keywords: Klebsiella pneumoniae; blaKPC variants; ceftazidime-avibactam.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Distribution of Klebsiella pneumoniae carbapenemase variants based on KPC-2 and KPC-3 mutations. The data are calculated based on the number of Klebsiella pneumoniae carbapenemase variants uploaded to the National Center for Biotechnology Information each year in each region (https://www.ncbi.nlm.nih.gov/).
Fig 2
Fig 2
KPC variants evolutionary tree analysis chart (A) and the number of new variants reported in PubMed over the years (B) (up to March 2023).
Fig 3
Fig 3
Ω-Loop destabilization as a mechanism of resistance to ceftazidime-avibactam. (A) Structure of KPC-2 (Protein Data Bank accession number 5UL8), Ω-Loop was shown in yellow; (B) hydrogen bonding network involving Ω-loop Arg and Asp residues in the WT KPC-2 (40); (C) Hydrogen bonding network involving Ω-loop Arg and Asp residues in D179N KPC-2 (40).
Fig 4
Fig 4
Genetic sequences surrounding blaKPC carbapenemase genes.
See this image and copyright information in PMC

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