Emergence of Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae with Penicillin-Binding Protein 3 Insertions, Taiwan, 2021

Carbapenem-resistant Enterobacterales (CRE) are a major global health threat with limited treatment options. Aztreonam/avibactam is a promising therapy against metallo-β-lactamase (MBL)-producing and other CRE, but emerging resistance threatens its effectiveness. Insertions in penicillin-binding protein 3 (PBP3), which are well described in Escherichia coli, are linked to reduced aztreonam/avibactam susceptibility but remain poorly characterized in Klebsiella pneumoniae. We report clinical K. pneumoniae carbapenemase-producing K. pneumoniae sequence type 11 isolates carrying a novel PBP3 YRIT insertion, conferring reduced susceptibility to aztreonam/avibactam and ceftazidime/avibactam. Functional and genetic studies suggest that the PBP3 insertion impairs β-lactam binding and, in combination with blaKPC-2 and other β-lactamases, contributes to reduced susceptibility. Those findings demonstrate the emergence of a PBP3 insertion in a high-risk K. pneumoniae clone, underscoring the expansion of this resistance mechanism and the critical need for genomic surveillance and novel therapeutics to identify and treat such infections.