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在台湾从血流感染患者中分离出的耐亚胺培南铜绿假单胞菌中,活性外排泵的过度产生和外膜孔蛋白D(OprD)的变异占主导地位。

Overproduction of active efflux pump and variations of OprD dominate in imipenem-resistant Pseudomonas aeruginosa isolated from patients with bloodstream infections in Taiwan.

作者信息

Kao Cheng-Yen, Chen Shu-Sheng, Hung Kuei-Hsiang, Wu Hsiu-Mei, Hsueh Po-Ren, Yan Jing-Jou, Wu Jiunn-Jong

机构信息

Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

BMC Microbiol. 2016 Jun 13;16(1):107. doi: 10.1186/s12866-016-0719-2.

DOI:10.1186/s12866-016-0719-2
PMID:27296461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4906909/
Abstract

BACKGROUND

The emergence of imipenem-resistant Pseudomonas aeruginosa (IRPA) has become a great concern worldwide. The aim of this study was to investigate resistance mechanisms associated with bloodstream isolated IRPA strains in Taiwan.

RESULTS

A total of 78 non-duplicated IRPA isolates were isolated from patients with bloodstream infection. The average prevalence of imipenem-resistance in those isolates was 5.9 % during a 10-year longitudinal surveillance in Taiwan. PFGE results showed high clonal diversity among the 78 isolates. VIM-2, VIM-3, OXA-10, and OXA-17 β-lactamases were identified in 2 (2.6 %), 3 (3.8 %), 2 (2.6 %), and 1 (1.3 %) isolates, respectively. Active efflux pumps, AmpC β-lactamase overproduction, and extended-spectrum AmpC cephalosporinases (ESACs) were found in 58 (74.4 %), 25 (32.1 %) and 15 (19.2 %) of IRPA isolates, respectively. oprD mutations with amino acid substitution, shortened putative loop L7, premature stop codon caused by point mutation, frameshift by nucleotide insertion or deletion, and interruption by insertion sequence were found in 19 (24.4 %), 18 (23.1 %), 15 (19.2 %), 14 (17.9 %), and 10 (12.8 %) of isolates, respectively.

CONCLUSIONS

This study suggests that alterations in the OprD protein and having an active efflux pump are the main mechanisms associated with bloodstream isolated IRPA. Overproduction of AmpC, ESACs, and the presence of VIM- and OXA-type β-lactamases play additional roles in reduced susceptibility to imipenem in P. aeruginosa isolates in Taiwan.

摘要

背景

耐亚胺培南铜绿假单胞菌(IRPA)的出现已成为全球关注的重大问题。本研究旨在调查台湾地区血流感染分离出的IRPA菌株的耐药机制。

结果

从血流感染患者中分离出78株非重复的IRPA菌株。在台湾为期10年的纵向监测中,这些菌株中亚胺培南耐药的平均发生率为5.9%。脉冲场凝胶电泳(PFGE)结果显示78株菌株间存在高度的克隆多样性。分别在2株(2.6%)、3株(3.8%)、2株(2.6%)和1株(1.3%)菌株中鉴定出VIM-2、VIM-3、OXA-10和OXA-17β-内酰胺酶。分别在58株(74.4%)、25株(32.1%)和15株(19.2%)的IRPA菌株中发现了主动外排泵、AmpCβ-内酰胺酶过量产生和超广谱AmpC头孢菌素酶(ESACs)。分别在19株(24.4%)、18株(23.1%)、15株(19.2%)、14株(17.9%)和10株(12.8%)菌株中发现了氨基酸替代的oprD突变、推定的L7环缩短、点突变导致的提前终止密码子、核苷酸插入或缺失导致的移码以及插入序列导致的中断。

结论

本研究表明,OprD蛋白改变和存在主动外排泵是与血流感染分离出的IRPA相关的主要机制。AmpC、ESACs的过量产生以及VIM型和OXA型β-内酰胺酶的存在在台湾地区铜绿假单胞菌分离株对亚胺培南敏感性降低中起额外作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ca/4906909/f0a3a1773dcb/12866_2016_719_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ca/4906909/f0a3a1773dcb/12866_2016_719_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ca/4906909/f0a3a1773dcb/12866_2016_719_Fig1_HTML.jpg

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