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中国携带超广谱β-内酰胺酶的耐多药菌株的出现及其分子特征与呼吸机相关性肺炎

Emergence and molecular characterization of multidrug-resistant isolates harboring extended-spectrum β-lactamases causing ventilator-associated pneumonia in China.

作者信息

Xu Hui, Huo Chunxiu, Sun Yao, Zhou Yiheng, Xiong Yilin, Zhao Zinan, Zhou Qi, Sha Li, Zhang Beibei, Chen Yang

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Infect Drug Resist. 2018 Dec 20;12:33-43. doi: 10.2147/IDR.S189494. eCollection 2019.

Abstract

BACKGROUND

Ventilator-associated pneumonia (VAP) is a common nosocomial infection associated with high morbidity due to multidrug-resistant (MDR) pathogens. The purpose of this study was to determine the occurrence of extended-spectrum β-lactamase (ESBL) genes, especially , in ()-associated VAP and to investigate the antimicrobial resistance patterns and molecular epidemiological characteristics of strains.

MATERIALS AND METHODS

From January 2013 to December 2015, we retrospectively collected 89 VAP-causing isolates from tertiary-care hospitals in China, among which ESBL-producing strains were assessed for antimicrobial susceptibility. Several antibiotic resistance genes of clinical relevance in isolates producing ESBL were investigated. Polymerase chain reaction (PCR) and DNA sequencing were employed to characterize the genetic contexts of . Conjugative plasmids carrying were obtained by mating and further subjected to replicon typing. The genetic relatedness of isolates was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.

RESULTS

All of the 30 ESBL-producing isolates identified displayed MDR phenotype, with , , , and detected in 21, 21, 1, and 20 isolates, respectively. was the most prevalent ESBL gene (19/30, 63.33%), and IS was detected 48 bp upstream of 15 genes. Based on S1-PFGE analyses, 25 isolates exhibited different plasmid profiles, ranging from ~70 to 320 kb. The with and genes and the IS element from eight isolates were co-transferrable to recipients via conjugation, with IncFIB, IncFIC, and IncFII being the most prevalent replicons. Twenty different PFGE patterns and 11 sequence types were identified, with ST304 being dominant.

CONCLUSION

This work reports the emergence of in -induced VAP in China. We showed that IncFIB, IncFIC, and/or IncFII plasmids carrying with , resistance genes, and the IS element mediate the local prevalence in associated VAP.

摘要

背景

呼吸机相关性肺炎(VAP)是一种常见的医院感染,因多重耐药(MDR)病原体导致高发病率。本研究的目的是确定超广谱β-内酰胺酶(ESBL)基因,尤其是在肺炎克雷伯菌(K. pneumoniae)相关性VAP中的发生情况,并调查肺炎克雷伯菌菌株的抗菌耐药模式和分子流行病学特征。

材料与方法

2013年1月至2015年12月,我们回顾性收集了来自中国三级医院的89株引起VAP的肺炎克雷伯菌分离株,其中对产ESBL菌株进行了抗菌药敏评估。研究了产ESBL肺炎克雷伯菌分离株中几种具有临床相关性的抗生素耐药基因。采用聚合酶链反应(PCR)和DNA测序来表征blaCTX-M的基因背景。通过接合获得携带blaCTX-M的接合质粒,并进一步进行复制子分型。通过脉冲场凝胶电泳(PFGE)和多位点序列分型评估分离株的遗传相关性。

结果

鉴定出的30株产ESBL分离株均表现出MDR表型,分别在21、21、1和20株分离株中检测到blaCTX-M-15、blaCTX-M-14、blaCTX-M-27和blaCTX-M-65。blaCTX-M-15是最常见的ESBL基因(19/30,63.33%),并且在15个blaCTX-M-15基因的上游48 bp处检测到ISEcp1。基于S1-PFGE分析,25株分离株表现出不同的质粒图谱,大小范围约为70至320 kb。来自8株分离株的携带blaCTX-M-15、blaTEM-1和blaSHV-12基因以及ISEcp1元件的质粒可通过接合共同转移至受体菌,IncFIB、IncFIC和IncFII是最常见的复制子。鉴定出20种不同的PFGE模式和11种序列类型,其中ST304占主导。

结论

本研究报道了中国肺炎克雷伯菌诱导的VAP中blaCTX-M-15的出现。我们表明,携带blaCTX-M-15、blaTEM-1和blaSHV-12耐药基因以及ISEcp1元件的IncFIB、IncFIC和/或IncFII质粒介导了肺炎克雷伯菌相关性VAP中的局部流行。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd72/6304254/1d633cf35311/idr-12-033Fig1.jpg

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