A large-scale surveillance revealed that KPC variants mediated ceftazidime-avibactam resistance in clinically isolated Klebsiella pneumoniae

作者：Sai Qiao, Shaojun Xin, Yufeng Zhu, Feng Zhao, Heng Wu, Jingjing Zhang, Bingyan Yao, Yunsong Yu, Ying Fu, Yan Jiang, Xinyou Xie, Jun Zhang · 发表于：Microbiology Spectrum · 年份：2024 · DOI：10.1128/spectrum.00258-24 · 被引用次数：4 · 研究领域：Antibiotic Resistance in Bacteria、Antibiotics Pharmacokinetics and Efficacy、Plant Pathogenic Bacteria Studies

ABSTRACT To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, we conducted over a 2-year surveillance focusing on the Klebsiella pneumoniae associated with the clinical usage of ceftazidime-avibactam (CZA) in a teaching hospital. A total of 4,641 K . pneumoniae isolates were screened to identify the CZA resistance through antimicrobial susceptibility testing. Comprehensive analyses, including homology analysis, conjugation experiments, clone assays, and whole genome sequencing, were furtherly performed on the CZA-resistant strains. In total, four CZA-resistant K. pneumoniae (CZA-R-Kp) strains were separated from four patients, in which three of them received CZA treatment during the hospitalization, accounting for a 4% (3/75) resistance development rate of K. pneumoniae under CZA stress. All CZA-R-Kp isolates were found to possess variants of bla KPC-2 . The identified mutations included bla KPC-33 , bla KPC-86 , and a novel variant designated as bla KPC-129 , all of which were located in the Ω loop of the KPC enzyme. These mutations were found to impact the amino acid sequence and spatial structure of the enzyme’s active center, consequently affecting KPC carbapenemase activity. This study underscores the importance of active surveillance to monitor the emergence of resistance to CZA, highlighting the need for ongoing research to develop effective strategies for combating antimicrobial resistance. Understanding the mechanisms behind re...