机构：[1]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China 苏州大学附属第二医院[2]Department of Clinical Laboratory, The Affiliated Peoples' Hospital of Ningbo University, Ningbo, Zhejiang, China [3]Department of Laboratory Medicine, Ningbo First Hospital, Ningbo, Zhejiang, China [4]Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China [5]Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China 中山大学附属第一医院[6]Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China 四川省人民医院[7]Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, China [8]Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 医技科室医学检验科昆明医科大学附属第一医院[9]Laboratory Medicine Center, Aviation General Hospital, Beijing, China [10]Department of Medical Affairs, Danaher Diagnostic Platform/Cepheid (China), New York, New York, USA [11]Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA [12]Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a & GE;8-fold decrease in colistin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), which indicated that heteroresistance could be suppressed by an efflux pump inhibitor. In addition, our results suggested that the PhoPQ pathway plays an important role in the mechanisms of heteroresistance.IMPORTANCE The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown. Importantly, colistin-heteroresistant strains may cause the failure of clinical treatment with colistin, even if the clinical laboratory reports that the strains are sensitive. The commonly used broth microdilution method is unable to detect this special phenomenon. Additionally, our results indicate that efflux pumps play a major role in colistin heteroresistance, and inhibitors can effectively reverse it. Our study is the first to provide a detailed analysis of the prevalence of colistin heteroresistance in China, as well as an analysis of the genetic mechanisms of this phenomenon. The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown.
基金：
Science Foundation of Jiangsu Province Health Department [ZDB2020014]; Science Foundation of Suzhou Health Department [LCZX202106]; Science and Technology Program of Suzhou [SLJ2022003, 2022SS41]; Discipline Construction Program of the Second Affiliated Hospital of Soochow University [XKTJ-TD202001]
第一作者机构：[1]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China [2]Department of Clinical Laboratory, The Affiliated Peoples' Hospital of Ningbo University, Ningbo, Zhejiang, China [3]Department of Laboratory Medicine, Ningbo First Hospital, Ningbo, Zhejiang, China
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通讯作者：
推荐引用方式(GB/T 7714)：
Weng Yuesong,Wang Tao,Huang Bin,et al.Multicenter Study of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Strains in China[J].MICROBIOLOGY SPECTRUM.2023,11(4):doi:10.1128/spectrum.02218-22.
APA：
Weng, Yuesong,Wang, Tao,Huang, Bin,Yu, Hua,Jia, Wei...&Du, Hong.(2023).Multicenter Study of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Strains in China.MICROBIOLOGY SPECTRUM,11,(4)
MLA：
Weng, Yuesong,et al."Multicenter Study of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Strains in China".MICROBIOLOGY SPECTRUM 11..4(2023)
