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中国血流感染碳青霉烯类耐药肺炎克雷伯菌的多中心基因组分析。

Multicenter Genomic Analysis of Carbapenem-Resistant Klebsiella pneumoniae from Bacteremia in China.

机构信息

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

Research Group in Basic and Applied Microbiology (MICROBA), School of Microbiology, University of Antioquia, Medellín, Colombia.

出版信息

Microbiol Spectr. 2022 Apr 27;10(2):e0229021. doi: 10.1128/spectrum.02290-21. Epub 2022 Mar 1.

DOI:10.1128/spectrum.02290-21
PMID:35230130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9045280/
Abstract

Klebsiella pneumoniae is one of the most common Gram-negative bacilli isolated from bloodstream infections worldwide, and recently an increased rate of carbapenem resistance has been reported in this pathogen. This study aims to describe the genomic characteristics of carbapenem-resistant K. pneumoniae (CRKP) isolated from patients with bacteremia in China. We analyzed 147 isolates from patients with bacteremia attended in 12 referral hospitals in China between April 2015 and November 2018. We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis to characterize antimicrobial resistance profile, virulence genes, and dominant clones among CRKP. ST11 accounted for most infections ( = 98, 66.6%), followed by ST45 ( = 12, 8.2%), ST15 and ST290 ( = 8, 5.4% each). KPC ( = 98, 66.7%) and NDM ( = 27, 18.4%) are the main carbapenemases detected in the CRKP isolates. We detected yersiniabactin ( = 123, 83.7%) and aerobactin (49.9%) siderophores, and both and aerobactin genes in 21 ST11 isolates (21.43%), which are considered characteristic biomarkers of hypervirulent strains. Isolates showed high resistance rates to the β-lactams (>90%) and other antibiotics classes such as fluoroquinolones, aminoglycosides and tetracyclines (50%), but were susceptible to ceftazidime-avibactam (74.8%). In addition, we detected intra-hospital transmission of ST11 and ST45 strains in single and multiple wards in several hospitals, whereas inter-hospital transmission was relatively uncommon. In summary, we observed significantly genomic diversity of CRKP bacteremia isolates in China, although KPC-2 producing ST11 strains were found to be the most common clonal types. Reducing intra-hospital transmission remains to be the key to control CRKP caused bloodstream infections in China. K. pneumoniae is one of the most frequent Gram-negative bacilli isolated from bloodstream infections worldwide and recent studies have shown an increased rate of carbapenem resistance in China. Among carbapenem-resistant K. pneumoniae (CRKP) diverse clones have been reported, especially the high-risk clone ST11, which also exhibited a multidrug resistant phenotype. In addition to the antimicrobial resistance, previous studies have detected strains co-harboring virulent traits, highlighting the potential of transmission of both antimicrobial resistant and virulent strains. Here we studied the antimicrobial resistance profile, virulence genes and hospital transmission of CRKP from bacteremic patients in China. This study showed a high clonal diversity among CRKP, with the predominance of ST11 lineages. We detected virulence markers among multidrug resistant strains, and a high number of genetically similar isolates, suggesting intra-hospital transmission within single and multiple wards. Reducing intra-hospital transmission remains to be the key to control CRKP caused bacteremia in China.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d65/9045280/bafcce7ff16e/spectrum.02290-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d65/9045280/76429b02df57/spectrum.02290-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d65/9045280/bafcce7ff16e/spectrum.02290-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d65/9045280/76429b02df57/spectrum.02290-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d65/9045280/bafcce7ff16e/spectrum.02290-21-f002.jpg
摘要

肺炎克雷伯菌是全球血流感染中最常见的革兰氏阴性杆菌之一,最近有报道称这种病原体的碳青霉烯类耐药率有所上升。本研究旨在描述中国血流感染患者分离的碳青霉烯类耐药肺炎克雷伯菌(CRKP)的基因组特征。我们分析了 2015 年 4 月至 2018 年 11 月期间在中国 12 家转诊医院就诊的 147 例菌血症患者的分离株。我们进行了表型药敏评估和全基因组序列分析,以描述 CRKP 的抗菌药物耐药谱、毒力基因和优势克隆。ST11 占大多数感染( = 98,66.6%),其次是 ST45( = 12,8.2%)、ST15 和 ST290( = 8,5.4%)。在 CRKP 分离株中,主要检测到 KPC( = 98,66.7%)和 NDM( = 27,18.4%)碳青霉烯酶。我们检测到耶尔森菌素( = 123,83.7%)和铁载体(49.9%),在 21 株 ST11 分离株(21.43%)中同时检测到耶尔森菌素和铁载体基因,这被认为是高毒力株的特征生物标志物。分离株对β-内酰胺类药物(>90%)和其他抗生素类药物(如氟喹诺酮类、氨基糖苷类和四环素类)表现出高度耐药率(>50%),但对头孢他啶-阿维巴坦(74.8%)敏感。此外,我们在多家医院的单个和多个病房中检测到 ST11 和 ST45 菌株的院内传播,而医院间传播相对较少。总之,我们观察到中国 CRKP 菌血症分离株的基因组多样性显著,尽管产 KPC-2 的 ST11 菌株被发现是最常见的克隆类型。减少院内传播仍然是控制中国 CRKP 引起血流感染的关键。

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