Shao Lingli, Yao Bei, Yang Jiyong, Li Xin, Ye Kun, Zhang Yanping, Wang Chengbin
Medical School of Chinese PLA & Department of Clinical Laboratory, Medical Laboratory Center, Chinese PLA General Hospital, Beijing 100853, China; Department of Clinical Laboratory, Beijing Northern Hospital of Weaponry Industry, Beijing 100089, China.
Department of Clinical Laboratory, Peking University Third Hospital, Beijing 100191, China.
Ann Palliat Med. 2020 May;9(3):1092-1102. doi: 10.21037/apm-20-958. Epub 2020 May 14.
The incidence of Klebsiella pneumonia (Kp), which has often been found to produce, extended spectrum beta-lactamase (ESBL), is rising rapidly and poses a serious risk to neonates. To date, the mechanisms related to the spread of ESBL-Kp have not been fully elucidated. This study aimed to investigate the phenotypes, genotypes, and genetic relatedness of ESBL-KP that caused an outbreak of sepsis among neonates in an intensive care unit of a Beijing hospital.
Between April 2016 and May 2018, 21 non-repetitive clinical ESBL-Kp isolates were collected from a neonatal intensive care unit (NICU) in Beijing, China and were retrospectively analyzed. Pulsed-field gel electrophoresis (PFGE) was used to analyze genetic relatedness, a VITEK 2 AST test kit was used to test antimicrobial susceptibility, sequence type (ST) was analyzed through multilocus sequence typing (MLST), and resistance genes were identified by PCR. Virulence gene profiles, biofilm formation assay, and serum killing assay were used for virulence-associated determinants.
All strains expressed the same antibiotype, combining ESBL production, third generation cephalosporins resistance and carbapenems sensitive. Sixteen of them produced β-lactamases (CTX-M-3 and TEM-1B), while others possessed CTX-M-15, CTX-M-24, CTX-M-66, TEM-1C, SHV-26, SHV172, and OXA-1. PFGE confirmed 5 types (A, B, C, D and E) and MLST identified a ST3330 clone (16 strains), a ST2791 clone (2 strains), a ST37 clone (1 strain), a ST34 clone (1 strain), and a ST2740 clone (1 strain). PFGE type A strains, which belong to ST3330, were identified as the main pathogens involved in the outbreak. All isolates contained virulence genes iutA and mrk. PFGE type A carried both mrk (type 3 fimbriae, biofilm formation) and fimH (type 1 fimbriae), and other STs possessed mrk. Isolates belonging to the endemic ST3330 lineage produced more biofilm than other ST isolates (median OD590 1.829 vs. 0.2280, respectively; P<0.0001). All five PFGE types isolates showed serum high sensitivity (grade 1).
The dissemination and outbreak of ESBL-producing K. pneumoniae in this study seemed to be clonal, and the outbreak was mainly caused by ST3330 K. pneumoniae. The detection of genes (mrk and fimH) belonging to the biofilm formation may partly explain the epidemic strain has high colonization and diffusion potential.
肺炎克雷伯菌(Kp)常产超广谱β-内酰胺酶(ESBL),其发病率迅速上升,对新生儿构成严重风险。迄今为止,与产ESBL-Kp传播相关的机制尚未完全阐明。本研究旨在调查在北京一家医院重症监护病房引起新生儿败血症暴发的产ESBL-KP的表型、基因型及遗传相关性。
2016年4月至2018年5月,从中国北京一家新生儿重症监护病房(NICU)收集21株非重复临床产ESBL-Kp分离株并进行回顾性分析。采用脉冲场凝胶电泳(PFGE)分析遗传相关性,使用VITEK 2 AST检测试剂盒检测抗菌药物敏感性,通过多位点序列分型(MLST)分析序列类型(ST),并通过PCR鉴定耐药基因。采用毒力基因谱、生物膜形成试验和血清杀菌试验检测毒力相关决定因素。
所有菌株表现出相同的抗菌谱型,即产ESBLs、对第三代头孢菌素耐药且对碳青霉烯类敏感。其中16株产生β-内酰胺酶(CTX-M-3和TEM-1B),其他菌株携带CTX-M-15、CTX-M-24、CTX-M-66、TEM-1C、SHV-26、SHV172和OXA-1。PFGE确定了5种类型(A、B、C、D和E),MLST鉴定出一个ST3330克隆(16株)、一个ST2791克隆(2株)、一个ST37克隆(1株)、一个ST34克隆(1株)和一个ST2740克隆(1株)。属于ST3330的PFGE A型菌株被确定为暴发的主要病原体。所有分离株均含有毒力基因iutA和mrk。PFGE A型携带mrk(3型菌毛,生物膜形成)和fimH(1型菌毛),其他ST型含有mrk。属于地方性ST3330谱系的分离株比其他ST型分离株产生更多生物膜(中位OD590分别为1.829和0.2280;P<0.0001)。所有5种PFGE类型的分离株均显示血清高敏感性(1级)。
本研究中产ESBL肺炎克雷伯菌的传播和暴发似乎是克隆性的,暴发主要由ST3330肺炎克雷伯菌引起。对生物膜形成相关基因(mrk和fimH)的检测可能部分解释了流行菌株具有高定植和扩散潜力。