Repeated insertions at positions 261-280 in KPC-2 highlight a ceftazidime-avibactam resistance hotspot.

We report the emergence of KPC-261, a KPC-2 variant identified in a Klebsiella pneumoniae strain exhibiting high-level resistance to ceftazidime-avibactam (CZA). Comparative sequence analysis revealed a repeated insertion event between amino acid positions 261-280, highlighting a mutational hotspot linked to reduced avibactam binding. Our findings uncover a structural mechanism driving CZA resistance and broaden our understanding of β-lactamase evolution.