The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae

doi:10.1093/jac/dkae174

科研成果详情

题名	The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae
作者	Xiaotuan Zhang1; Weiliang Zeng1; Jingchun Kong2; Zeyu Huang1; Hongyun Shu1; Miran Tang1; Changrui Qian 1; Chunquan Xu1; Tieli Zhou1; Jianzhong Ye1
发表日期	2024-06-06
发表期刊	The Journal of antimicrobial chemotherapy 影响因子和分区
语种	英语
原始文献类型	Journal Article
其他关键词	AVIBACTAM RESISTANCE ; EPIDEMIOLOGY ; VIRULENCE ; EMERGENCE
摘要	To investigate the prevalence and mechanisms of ceftazidime/avibactam heteroresistance in KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, as well as the role of heteroresistance in the transition of ceftazidime/avibactam susceptibility to resistance., Clinical KPC-KP isolates were obtained from a tertiary hospital in China from 2016 to 2017 and 2019 to 2020. Antimicrobial susceptibility was determined by the broth microdilution method. Population analysis profiles were used to assess ceftazidime/avibactam heteroresistance. WGS and molecular cloning were conducted to reveal heteroresistance mechanisms and molecular characteristics., The findings indicated that the transition of ceftazidime/avibactam susceptibility to resistance during the treatment of KPC-KP infection is primarily attributed to the heteroresistance exhibited by KPC-KP isolates towards ceftazidime/avibactam. Among 355 ceftazidime/avibactam-susceptible KPC-KP isolates (indicating a resistance rate of 0%), 41 (11.55%) exhibited ceftazidime/avibactam heteroresistance, with the primary mechanism being the presence of KPC mutant subpopulations. These KPC variants, arising from point mutations, deletions and insertions, significantly increased ceftazidime/avibactam resistance while alongside enhanced carbapenem susceptibility. Notably, 11 new KPC variants were identified. Furthermore, four heteroresistant isolates were caused by mixed infection involving subpopulations carrying NDM-1 or NDM-5. Phylogenetic analysis indicated that the clonal spread of ST11-KL64 KPC-KP may be correlated with the prevalence of heteroresistance., Ceftazidime/avibactam heteroresistance, primarily driven by pre-existing KPC variants, underscores the importance of considering heteroresistance in ceftazidime/avibactam therapeutics. Awareness of these dynamics is crucial for the effective and sustainable clinical application of ceftazidime/avibactam.
资助项目	Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province[2022E10022];Scientific Research Project of Department of Education of Zhejiang Province of China[Y202250154]
出版者	OXFORD UNIV PRESS
ISSN	0305-7453
EISSN	1460-2091
卷号	79 期号:8 页码:1865-1876
DOI	10.1093/jac/dkae174
页数	12
WOS类目	Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
WOS研究方向	Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
WOS记录号	WOS:001241820400001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38842536
SCOPUSEID	2-s2.0-85200253221
通讯作者地址	[Ye, Jianzhong]Wenzhou Med Univ, Affiliated Hosp 1, Dept Clin Lab, Key Lab Clin Lab Diag & Translat Res Zhejiang Pro, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Pharmacology;Microbiology (medical);Pharmacology (medical);Infectious Diseases
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/215101
专题	附属第一医院检验医学院（生命科学学院、生物学实验教学中心）第一临床医学院（信息与工程学院）、附属第一医院检验医学院（生命科学学院、生物学实验教学中心）_基础检验学系第一临床医学院（信息与工程学院）、附属第一医院_临床检验诊断学
作者单位	1.Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.; 2.Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
第一作者单位	附属第一医院; 临床检验诊断学; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Xiaotuan Zhang,Weiliang Zeng,Jingchun Kong,et al. The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae[J]. The Journal of antimicrobial chemotherapy,2024,79(8):1865-1876.
APA	Xiaotuan Zhang., Weiliang Zeng., Jingchun Kong., Zeyu Huang., Hongyun Shu., ... & Jianzhong Ye. (2024). The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae. The Journal of antimicrobial chemotherapy, 79(8), 1865-1876.
MLA	Xiaotuan Zhang,et al."The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae".The Journal of antimicrobial chemotherapy 79.8(2024):1865-1876.