Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms

Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms
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中国多中心研究中肠球菌和科尼葡萄球菌的利奈唑胺耐药临床分离株:分子流行病学和耐药机制

DOI:
10.1016/j.ijantimicag.2013.06.008
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发表时间:
2013-10-01
影响因子:
10.8
通讯作者:
Wang, Hui
Wang, Hui
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Hongbin;Wu, Weiyuan;Wang, Hui

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在中国的一项多中心研究中,耐利奈唑胺的革兰氏阳性球菌的基因特征此前未见报道。为探讨利奈唑胺耐药株的耐药机制,从2009年至2012年从中国全市5所医院收集了9株不同程度耐药的粪肠球菌、1株屎肠球菌和3株科氏葡萄球菌。将9株粪肠球菌分为7个序列类型,表明这些粪肠球菌对利奈唑胺耐药是多克隆的。肠球菌对利奈唑胺的敏感性降低(MIC为48 mg/L),核糖体蛋白L3发生突变,其中3株也有L4突变,但未发现多药耐药基因cfr或23S rRNA突变G2576T。3株科氏链球菌对利奈唑胺高度抗性(mg/L对&GT的MIC为256 mg/L),携带cfr基因,并存在23S rRNA突变G2576T。Southern杂交结果表明,这3个菌株的CFR基因分别位于不同的质粒(pHK01、pRM01和pRA01)上。在pHK01中,IS21-558和CFR基因被整合到转座子Tn558中。在质粒pRM01和pRA01中,CFR基因两侧有两个拷贝的类似IS256的插入序列,这表明可转移形式的利奈唑胺抗性是由CFR基因决定的。总之,中国不同地区对利奈唑胺耐药的革兰氏阳性球菌的出现值得关注。Cfr基因和23S rRNA突变与科氏链球菌对利奈唑胺高度耐药有关,而L3和L4突变与肠球菌对利奈唑胺的低水平耐药有关。(C)2013年爱思唯尔公司和国际化疗学会。版权所有。
Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 48 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci. (C) 2013 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.