Emergence of Tigecycline-Nonsusceptible Carbapenem-Resistant Klebsiella pneumoniae with Metallo-β-Lactamase and Transferable Ceftazidime-Avibactam Resistance in China

In recent years, resistance of <i>Klebsiella pneumoniae</i> to the clinical last-resort drugs carbapenem and tigecycline has intensified, including Metallo-β-Lactamase-producing <i>K. pneumoniae</i> (MBL-KP), which demonstrated resistance to ceftazidime-avibactam (CZA), posing a significant public health threat. This study focused on the carbapenems, CZA, and tigecycline resistance mechanisms of MBL-producing Carbapenem-resistant <i>K. pneumoniae</i> (MBL-CRKP). A retrospective study and genomic epidemiological analysis of Carbapenem-resistant <i>K. pneumoniae</i> (CRKP) strains isolated from Yangzhou City, Jiangsu Province, China, between 2016 and 2023 was conducted. The detection rate of CRKP in Yangzhou City has increased significantly in recent years, with five strains carrying the Metallo-β-Lactamases (MBLs) gene, all of which exhibited resistance to carbapenems and CZA. Two strains even showed reduced susceptibility to tigecycline, with one harboring <i>tmexCD2-toprJ2</i>. Moreover, three CRKP strains carrying both <i>bla</i>_KPC-2 and <i>bla</i>_NDM-1/<i>bla</i>_NDM-29 genes were identified. Plasmids carrying MBL genes can horizontally transfer, leading to the spread of resistance, thus further exacerbating the difficulty of clinical treatment and the spread of resistance. In conclusion, this study not only revealed the resistance of MBL-CRKP strains to clinical last-resort therapeutic drugs but also explored the resistance mechanism and horizontal transfer through genomic analysis. Moreover, this study also suggested that microbial drug resistance surveillance should be conducted from the perspective of "one health" in the future to combat this global health challenge.