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产碳青霉烯酶肺炎克雷伯菌血流感染:老药遇上“狠角色”。

Colistin-resistant Klebsiella pneumoniae bloodstream infection: old drug, bad bug.

机构信息

Shaare Zedek Medical Center, Department of Infectious Diseases, Jerusalem, Israel.

Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

出版信息

Arch Microbiol. 2021 Aug;203(6):2999-3006. doi: 10.1007/s00203-021-02289-4. Epub 2021 Mar 27.

DOI:10.1007/s00203-021-02289-4
PMID:33774687
Abstract

Multi-drug-resistant (MDR) Enterobacteriaceae pose a global threat to hospitalized patients. We report a series of colistin-resistant Klebsiella pneumoniae blood isolates from Israel and explore their resistance mechanisms using whole genome sequencing (WGS). Patients with colistin-resistant K. pneumoniae bloodstream infection (BSI) were identified during the period between 2006 and 2018. Demographic and clinical data were collected, and antibiotic susceptibility testing (AST) was performed using three commercial platforms. Long and short read sequencing were performed on a PacBio RS II (Pacific Biosciences) and an Illumina Miseq (Illumina), respectively. Thirteen patients with colistin-resistant K. pneumoniae BSI were identified, and seven isolates from seven different patients were successfully revived. Patient records indicated that five of the patients were previously treated with colistin. AST indicated that six of the seven isolates were colistin resistant and four of these isolates were resistant to carbapenems. WGS assigned the isolates to four distinct clusters that corresponded to in silico-derived multi-locus sequence types (MLST). Three isolates carried blaon two different plasmids and one carried bla on a novel IncL/M plasmid. All colistin-resistant isolates carried a variety of different mutations that inactivated the mgrB gene. We report the first comprehensive analysis of a series of colistin-resistant K. pneumoniae from Israel. A diverse set of isolates were obtained and colistin resistance was found to be attributed to different mechanisms that ablated the mgrB gene. Notably, carbapenemase genes were identified in four isolates and were carried on novel plasmids.

摘要

多药耐药(MDR)肠杆菌科对住院患者构成全球威胁。我们报告了一系列来自以色列的粘菌素耐药肺炎克雷伯菌血培养分离株,并通过全基因组测序(WGS)探索其耐药机制。在 2006 年至 2018 年期间,鉴定出患有粘菌素耐药肺炎克雷伯菌血流感染(BSI)的患者。收集了人口统计学和临床数据,并使用三种商业平台进行抗生素敏感性测试(AST)。分别在 PacBio RS II(Pacific Biosciences)和 Illumina Miseq(Illumina)上进行长读和短读测序。鉴定出 13 例粘菌素耐药肺炎克雷伯菌 BSI 患者,7 例来自 7 例不同患者的分离株成功复活。患者记录表明,5 例患者之前接受过粘菌素治疗。AST 表明,7 株分离株中有 6 株对粘菌素耐药,其中 4 株对碳青霉烯类耐药。WGS 将分离株分为四个不同的簇,与基于计算机的多位点序列分型(MLST)相对应。3 株携带 bla on 两个不同的质粒,1 株携带 bla on 一个新的 IncL/M 质粒。所有粘菌素耐药分离株均携带多种不同的突变,使 mgrB 基因失活。我们报告了一系列来自以色列的粘菌素耐药肺炎克雷伯菌的首次全面分析。获得了一组多样化的分离株,发现粘菌素耐药性归因于不同的机制,这些机制使 mgrB 基因失活。值得注意的是,在 4 株分离株中发现了碳青霉烯酶基因,这些基因位于新的质粒上。

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本文引用的文献

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ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads.ARIBA:直接从测序读段进行快速抗菌药物耐药基因分型。
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多重耐药菌的分子分型方法及耐药机制
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Genomic Epidemiology of Carbapenemase-Producing and Colistin-Resistant among Sepsis Patients in Ethiopia: a Whole-Genome Analysis.埃塞俄比亚败血症患者中产碳青霉烯酶和多粘菌素耐药菌的基因组流行病学:全基因组分析。
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