Epidemiological and genetic profiles of ceftazidime/avibactam-resistant Klebsiella pneumoniae conferred by KPC variants in a tertiary hospital in China.

Objective: The emergence of Klebsiella pneumoniae carbapenemase variants (KPCVs), conferring resistance to ceftazidime/avibactam (CAZ/AVI), represents a critical clinical challenge. However, investigations into KPCV-producing K. pneumoniae (KPCV-Kp) are confined to sporadic clinical cases.

Methods: Clinical isolates of KPCV-Kp exhibiting resistance to CAZ/AVI were collected from a Chinese tertiary hospital from February 2015 to March 2024. The clinical characteristics, antimicrobial susceptibility, molecular epidemiology and genetic phylogeny were subjected to analysis.

Results: A total of 25 KPCV-Kp strains displaying high-level resistance to CAZ/AVI were identified, with their initial isolation in 2018 and the majority obtained in 2023 (64.0%, 16/25). All patients except one had prior CAZ/AVI exposure for 3 to 38 days. Twelve KPCVs, including four novel variants (designated as KPC-219 to KPC-222), were identified. KPC-33 predominated (40.0%, 10/25), followed by KPC-71 (12.0%, 3/25), KPC-14, and KPC-90 (8.0%, 2/25 for each). Notably, 50.0% (6/12) of the KPCVs exhibited multiple mutations in the Ω-loop as well as in other regions, which were associated with a significantly longer CAZ/AVI exposure (P = 0.033). Molecular analysis highlighted the circulation of ST11-KL64 clone (72.0%, 18/25), followed by ST11-KL47 and ST11-KL25 clones (12.0%, 3/25 for each). Phylogenetic analysis revealed no epidemiological linkage between cases, and the KPCV-Kp evolved from their individual parental KPC-2-producing strains.

Conclusions: Our study provided a preliminary glimpse into the epidemiology and genetic characteristics of KPCV-Kp in China, underscoring the critical need for continuous monitoring in patients treated with CAZ/AVI, even in short-term therapy, to better grasp the evolving threat posed by these variants.