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儿童重症监护病房肺炎克雷伯菌中的克隆传播与水平传播

Clonal and Horizontal Transmission of among Klebsiella pneumoniae in Children's Intensive Care Units.

作者信息

Fu Bo, Yin Dandan, Sun Chengtao, Shen Yingbo, Liu Dejun, Bai Rina, Zhang Rong, Shen Jianzhong, Hu Fupin, Wang Yang

机构信息

Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural Universitygrid.22935.3f, Beijing, People's Republic of China.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Microbiol Spectr. 2022 Aug 31;10(4):e0157421. doi: 10.1128/spectrum.01574-21. Epub 2022 Jun 27.

DOI:10.1128/spectrum.01574-21
PMID:35758676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9431529/
Abstract

Increasing infections caused by -carrying Klebsiella pneumoniae (NDM-KP) are an urgent threat to children with weakened immunity and limited antibiotic use. Preventing and intervening in NDM-KP infections requires a clear understanding of the pathogen's molecular and epidemiological characteristics. We investigated the prevalence and characteristics of NDM-KP in six children's hospitals from five Chinese provinces/municipalities. We collected 111 NDM-KP strains (40 NDM-1, one NDM-4 and 70 NDM-5) from neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs) from June 2017 to June 2018; these strains accounted for 31.62% of all carbapenem-resistant K. pneumoniae (CR-KP). Although NDM-KP isolates exhibited high resistance to all carbapenems, including ertapenem (MIC: ≥32 mg/L, 96.4%), imipenem (MIC: ≥16 mg/L, 90.1%) and meropenem (MIC: ≥16 mg/L, 99.1%), they were fully sensitive to amikacin, tigecycline and polymyxin B, and presented low resistance to levofloxacin (9.9%) and gentamicin (15.3%). Whole-genome sequencing was conducted to gain insight into the molecular characterizations of NDM-KP isolates. The NDM-KP isolates belonged to 20 sequence types (STs), and ST2407 ( = 45) dominated in one hospital from Chengdu. ST2407 isolates with fewer single-nucleotide polymorphisms (SNP < 38) were found either in the same hospital or different hospitals. Most (81.1%, 90/111), including all and and 47.5% (19/40) of , in NDM-KP isolates with 13 STs were associated with the IncX3 plasmid. Our results indicated that both explosive clonal transmission and horizontal transmission of occur among NDM-KP strains in children's hospitals. These data provide a basis for preventing and controlling NDM-KP-associated infectious diseases in hospitalized children, especially in neonates. The gene is playing an increasingly important role in infections caused by CR-KP, especially in children. However, systematic detection and bioinformatics analysis of NDM-KP in children's hospitals are lacking in China. In this study, a total of 111 NDM-positive K. pneumoniae isolates were selected from the China Antimicrobial Surveillance Network for further investigation. The isolates were further characterized using state-of-the-art molecular techniques. Our findings suggested the clonal and horizontal transmission of in K. pneumoniae in NICUs/PICUs. Key plasmids (IncX3) and ST diversity contribute to the spread of . In addition, our findings provided recommendations for pediatric clinicians to use antibiotics to treat NDM-KP infections. Our current large-scale epidemiological survey would support further infection intervention strategies of NDM-KP in NICU/PICU of children's hospitals.

摘要

携带新德里金属β-内酰胺酶(NDM)的肺炎克雷伯菌(NDM-KP)导致的感染日益增多,这对免疫力较弱且抗生素使用受限的儿童构成了紧迫威胁。预防和干预NDM-KP感染需要清楚了解该病原体的分子和流行病学特征。我们调查了来自中国五个省/直辖市的六家儿童医院中NDM-KP的流行情况和特征。2017年6月至2018年6月期间,我们从新生儿重症监护病房(NICU)和儿科重症监护病房(PICU)收集了111株NDM-KP菌株(40株NDM-1、1株NDM-4和70株NDM-5);这些菌株占所有耐碳青霉烯类肺炎克雷伯菌(CR-KP)的31.62%。尽管NDM-KP分离株对所有碳青霉烯类药物均表现出高度耐药性,包括厄他培南(MIC:≥32mg/L,96.4%)、亚胺培南(MIC:≥16mg/L,90.1%)和美罗培南(MIC:≥16mg/L,99.1%),但它们对阿米卡星、替加环素和多粘菌素B完全敏感,对左氧氟沙星(9.9%)和庆大霉素(15.3%)的耐药性较低。进行全基因组测序以深入了解NDM-KP分离株的分子特征。NDM-KP分离株属于20种序列类型(STs),其中ST2407(n = 45)在成都的一家医院中占主导地位。在同一家医院或不同医院中均发现了单核苷酸多态性较少(SNP < 38)的ST2407分离株。在具有13种STs的NDM-KP分离株中,大多数(81.1%,90/111),包括所有的NDM-1和NDM-4以及47.5%(19/40)的NDM-5,与IncX3质粒相关。我们的结果表明,NDM在儿童医院的NDM-KP菌株中既存在爆发性克隆传播,也存在水平传播。这些数据为预防和控制住院儿童尤其是新生儿中与NDM-KP相关的传染病提供了依据。NDM基因在CR-KP引起的感染中,尤其是在儿童中,正发挥着越来越重要的作用。然而,中国儿童医院对NDM-KP缺乏系统的检测和生物信息学分析。在本研究中,从中国抗菌药物监测网络中总共选取了111株NDM阳性肺炎克雷伯菌分离株进行进一步调查。使用最先进的分子技术对这些分离株进行了进一步表征。我们的研究结果提示了NDM在NICU/PICU中的肺炎克雷伯菌中的克隆传播和水平传播。关键质粒(IncX3)和ST多样性促进了NDM的传播。此外,我们的研究结果为儿科临床医生使用抗生素治疗NDM-KP感染提供了建议。我们目前的大规模流行病学调查将支持儿童医院NICU/PICU中NDM-KP进一步的感染干预策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/7d7cb4e5aed1/spectrum.01574-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/760cc2ac0c94/spectrum.01574-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/747457fe97f3/spectrum.01574-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/0ab33637a0fd/spectrum.01574-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/7d7cb4e5aed1/spectrum.01574-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/760cc2ac0c94/spectrum.01574-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/747457fe97f3/spectrum.01574-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/0ab33637a0fd/spectrum.01574-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9431529/7d7cb4e5aed1/spectrum.01574-21-f004.jpg

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