Emergence of transferable ceftazidime–avibactam resistance in KPC-producing Klebsiella pneumoniae due to a novel CMY AmpC β-lactamase in China. (January 2022)

• Record Type: Journal Article
• Authors: Xu, Min; Zhao, Jun; Xu, Li; Yang, Qing; Xu, Hao; Kong, Haishen; Zhou, Jianying; Fu, Yiqi
• Is Part Of: Clinical microbiology and infection. Volume 28:Number 1(2022)
• Page Start: 136.e1
• Page End: 136.e6
• Publication Date: 2022-01
• Subjects: Avibactam -- CMY -- Klebsiella pneumoniae -- KPC -- Plasmid; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2021.05.026
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: Objectives: To evaluate the molecular mechanisms of ceftazidime/avibactam (CAZ/AVI) resistance in six Klebsiella pneumoniae strains that co-produce K. pneumoniae carbapenemase (KPC)-2 and a novel variant of CMY cephalosporinase in a Chinese hospital. Methods: Antimicrobial susceptibility was determined by broth microdilution. Whole-genome sequencing (WGS) was performed to investigate potential resistance determinants. Plasmid conjugation, electroporation, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) hybridization and cloning experiment were carried out to investigate the resistance plasmids and genes. Results: A high level of CAZ/AVI resistance was observed in six KPC-Kp strains (MIC 128 mg/L). Five strains were isolated in 2015 and one in 2016, before the approval of CAZ/AVI in China. Sequence analysis indicated that all the strains belonged to sequence type (ST) 11 and uniformly carried a novel CMY AmpC β-lactamase gene, designated bla CMY-172 . When compared with CMY-2, CMY-172 has a deletion of three consecutive amino acids (K290, V291 and A292) in the R2-loop region and a non-synonymous amino acid substitution at position 346 (N 346 I). The bla CMY-172 -bearing plasmid, pKPCZA02_4, was 93.3 Kb, IncI1-I type, and conjugative; bla CMY-172 was located in an IS 1294 -mediated transposon. Plasmid conjugation and DNA fragment cloning proved that bla CMY-172 was responsible for CAZ/AVI resistance. Conclusions: Our study identified conjugative plasmid-mediated bla CMY-172 as a new mechanism for CAZ/AVI resistance in clinical KPC-Kp strains. Careful monitoring of CAZ/AVI susceptibility is imperative for preventing the spread of the resistance gene.