Genomic Epidemiology and Ceftazidime-avibactam Resistance Mechanism of KPC-3-producing Pseudomonas aeruginosa: A Decade Retrospective Study in China.

Authors

Longjie Zhou, Zhiqiang Zhu, Xiaofei Zhao, Lu Ye, Linfang Wang, Jiaqing Wang, Haotian Xu, Qianhao Liu, Yuexing Tu, Minhua Chen, Xi Li

Published in

International journal of antimicrobial agents. Pages 107972. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CRPA), especially KPC-producing P. aeruginosa (KPC-PA), is rapidly expanding and posing a serious public health threat. Here, we aim to characterise the epidemiology of KPC-3-producing P. aeruginosa in a tertiary hospital over a 10-year period and elucidate the mechanism of ceftazidime-avibactam (CZA) resistance driven by bla_KPC-3 to bla_KPC-267 mutations in CRPA, along with conducting a global phylogeographic analysis of KPC-3-producing P. aeruginosa. All 11 KPC-3-producing CRPA strains in this study belonged to ST1076 and were resistant to ceftazidime, cefepime, meropenem, and imipenem, displaying a multiple-drug resistance phenotype. The bla_KPC-267-positive CZA-resistant strain SRMPA3523 was isolated from patient 1 after bla_KPC-3-positive P. aeruginosa SRMPA1139 and SRMPA1630 were treated with CZA. Whole-genome sequencing indicated that bla_KPC-3/267 was located on the Tn6296 transposon contained in the IncP-2 plasmid, which could be transferred into P. aeruginosa PAO1^Rif. KPC-267 mediates resistance to CZA by reducing the inhibitory effect of avibactam and increasing affinity for ceftazidime. Global analysis indicated that bla_KPC-3-carrying P. aeruginosa were predominantly in China, America, and Colombia, with ST1076 and ST111 as dominant clones. In conclusion, our study characterised the global phylogeography of bla_KPC-3-carrying P. aeruginosa and first reported the KPC-267 variant, which converted from KPC-3. This finding highlighted the risk of developing CZA resistance in KPC-PA strains under therapeutic pressure.

PMID:
42628850
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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