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Characteristic of KPC-12, a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in the Carbapenem-Resistant Klebsiella pneumoniae ST11-KL47 Clone Background.
Han, Weihua; Zhou, Peiyao; Chen, Chun; Wu, Chunyang; Shen, Li; Wan, Cailing; Xiao, Yanghua; Zhang, Jiao; Wang, Bingjie; Shi, Junhong; Yuan, Xinru; Gao, Haojin; Wang, Hongxiu; Zhou, Ying; Yu, Fangyou.
Afiliação
  • Han W; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Zhou P; Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
  • Chen C; Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, People's Republic of China.
  • Wu C; Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
  • Shen L; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Wan C; School of Public Health, Nanchang University, Nanchang, People's Republic of China.
  • Xiao Y; School of Public Health, Nanchang University, Nanchang, People's Republic of China.
  • Zhang J; Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
  • Wang B; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Shi J; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Yuan X; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Gao H; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Wang H; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Zhou Y; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • Yu F; Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Infect Drug Resist ; 17: 2541-2554, 2024.
Article em En | MEDLINE | ID: mdl-38933778
ABSTRACT

Background:

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective ß-lactam/ß-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae.

Methods:

The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.

Results:

Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 µg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of bla KPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.

Discussion:

Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying bla KPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Infect Drug Resist Ano de publicação: 2024 Tipo de documento: Article País de publicação: Nova Zelândia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Infect Drug Resist Ano de publicação: 2024 Tipo de documento: Article País de publicação: Nova Zelândia