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中国上海儿童患者分离的耐碳青霉烯类肺炎克雷伯菌的分子流行病学和耐药机制研究。

Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.

机构信息

Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.

Department of Ophthalmology, The Second People's Hospital of Foshan, Guangdong, P.R. China.

出版信息

PLoS One. 2018 Mar 20;13(3):e0194000. doi: 10.1371/journal.pone.0194000. eCollection 2018.

Abstract

Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent genotypes in adults in the same region. Knowledge of the molecular epidemiology and drug resistant mechanism of CR-KP can have a profound effect on clinical treatment, infection control measures and public health policies for children.

摘要

耐碳青霉烯肺炎克雷伯菌(CR-KP)感染是一个全球性的公共卫生挑战,尤其是在儿童中,其发病率和死亡率很高。儿科人群的数据有限,因此本研究旨在调查中国上海儿科患者的 CR-KP 菌株的分子流行病学和耐药机制。2014 年 7 月至 2015 年 5 月期间,在上海儿童医学中心共采集了 41 例来自痰、尿、血或引流液的临床耐碳青霉烯肺炎克雷伯菌分离株。对所有这些分离株进行了多位点序列分型(MLST)、抗生素药敏试验、耐药相关基因的 PCR 扩增和测序。MLST 分析显示,在 41 株分离株中发现了 16 个不同的 ST,其中最常见的是 ST11(19.5%)、ST25(14.6%)、ST76(14.6%)、ST37(9.8%)。首次发现了一种新的 ST。所有 CR-KP 分离株均表现出 MDR 表型,对头孢他啶、亚胺培南、哌拉西林/他唑巴坦、头孢曲松、氨苄西林/舒巴坦和氨曲南耐药。它们被确认为碳青霉烯酶产生菌,检测到 NDM-1(56.1%,23/41)、IMP(26.8%,11/41)和 KPC-2(22.0%,9/41)。值得注意的是,有两株分离株同时携带 NDM-1 和 IMP-4。所有 CR-KP 菌株均至少携带一种经测试的扩展谱β-内酰胺酶基因(TEM、SHV、OXA-1、CTX-M 组),有 6 株分离株同时携带 ESBL 和 AmpC 基因(DHA-1)。在青霉素酶和β-内酰胺酶基因中,最常见的是 SHV(92.7%,38/41),其次是 TEM-1(68.3%,28/41)、CTX-M-14(43.9%,18/41)、CTX-M-15(43.9%,14/41)和 OXA-1(14.6%,6/41)。在本研究中,NDM-1 产生的分离株是儿童中主要的 CR-KP 菌株,其次是 IMP 和 KPC 产生的分离株。NDM-1 和 IMP-4 比 KPC-2 更常见,且表现出多克隆背景。这表明儿童中的碳青霉烯耐药是多样的,某些耐药机制与同一地区成人中流行的基因型不同。了解 CR-KP 的分子流行病学和耐药机制对儿童的临床治疗、感染控制措施和公共卫生政策有深远的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4629/5860732/fa11509bcb21/pone.0194000.g001.jpg

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