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肺炎克雷伯菌 11 型对碳青霉烯类的耐药性与 DHA-1 及 OmpK35 和/或 OmpK36 的缺失有关。

Resistance to carbapenems in sequence type 11 Klebsiella pneumoniae is related to DHA-1 and loss of OmpK35 and/or OmpK36.

机构信息

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

J Med Microbiol. 2012 Feb;61(Pt 2):239-245. doi: 10.1099/jmm.0.037036-0. Epub 2011 Sep 22.

Abstract

This study investigated the molecular mechanisms of carbapenem resistance in clinical isolates of Klebsiella pneumoniae from Korea and the clinical outcomes of resistant K. pneumoniae infection. Sixteen K. pneumoniae isolates showing resistance to carbapenems collected from a tertiary-care hospital were examined for the mechanisms of carbapenem resistance. PCR and sequencing experiments detected the bla(DHA-1) AmpC β-lactamase gene in all 16 clinical isolates, whilst the bla genes of extended-spectrum β-lactamases were detected in 12 of 16 isolates. SDS-PAGE experiments indicated that all the isolates lacked the 35 kDa and/or 36 kDa outer-membrane proteins (OMPs). Sequence analysis of the corresponding OMP genes revealed various alterations. PFGE analysis demonstrated that there were no major clonal relationships among the K. pneumoniae isolates. However, multilocus sequence typing experiments showed that all isolates shared the same sequence type (ST), ST11, except for one isolate of ST48. The crude mortality rate of infected patients was 81.8 %. Carbapenem resistance was mainly due to a combination of DHA-1 AmpC β-lactamase coupled with the loss of OmpK35 and/or OmpK36 and was associated with poor clinical outcome.

摘要

本研究旨在探究韩国临床分离的肺炎克雷伯菌对碳青霉烯类药物耐药的分子机制及其耐药菌株感染的临床结局。从一家三级医院收集了 16 株对碳青霉烯类药物耐药的肺炎克雷伯菌临床分离株,用于研究其耐药机制。PCR 和测序实验检测到所有 16 株临床分离株均携带 bla(DHA-1)AmpC β-内酰胺酶基因,而 16 株中有 12 株携带了超广谱β-内酰胺酶基因。SDS-PAGE 实验表明,所有分离株均缺乏 35 kDa 和/或 36 kDa 的外膜蛋白(OMPs)。相应的 OMP 基因序列分析显示存在各种改变。PFGE 分析表明,这些肺炎克雷伯菌分离株之间没有主要的克隆关系。然而,多位点序列分型实验表明,除了一株 ST48 型分离株外,所有分离株均携带相同的 ST11 型序列。感染患者的粗死亡率为 81.8%。碳青霉烯类药物耐药主要是由于 DHA-1 AmpC β-内酰胺酶的存在,同时伴有 OmpK35 和/或 OmpK36 的缺失,与不良的临床结局相关。

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