Longjie Zhou, Zhiqiang Zhu, Xiaofei Zhao, Lu Ye, Linfang Wang, Jiaqing Wang, Haotian Xu, Qianhao Liu, Yuexing Tu, Minhua Chen, Xi Li
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 blaKPC-3 to blaKPC-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 blaKPC-267-positive CZA-resistant strain SRMPA3523 was isolated from patient 1 after blaKPC-3-positive P. aeruginosa SRMPA1139 and SRMPA1630 were treated with CZA. Whole-genome sequencing indicated that blaKPC-3/267 was located on the Tn6296 transposon contained in the IncP-2 plasmid, which could be transferred into P. aeruginosa PAO1Rif. KPC-267 mediates resistance to CZA by reducing the inhibitory effect of avibactam and increasing affinity for ceftazidime. Global analysis indicated that blaKPC-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 blaKPC-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.