Fu Bo, Yin Dandan, Sun Chengtao, Shen Yingbo, Liu Dejun, Bai Rina, Zhang Rong, Shen Jianzhong, Hu Fupin, Wang Yang
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.
Microbiol Spectr. 2022 Aug 31;10(4):e0157421. doi: 10.1128/spectrum.01574-21. Epub 2022 Jun 27.
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.
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。