Emergence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacterales in Spain studied by whole-genome sequencing

Emergence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacterales in Spain studied by whole-genome sequencing
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DOI:
10.1016/j.ijantimicag.2021.106456
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发表时间:
2022-01-11
影响因子:
10.8
通讯作者:
Bou, German
Bou, German
中科院分区:
医学2区
文献类型:
--
作者:
Arca-Suarez, Jorge;Rodino-Janeiro, Bruno K.;Bou, German

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16 S rRNA甲基转移酶(RMT)在具有其他临床相关耐药机制的革兰氏阴性病原体(例如产碳青霉烯酶的肠球菌目(CPE))中的出现正成为令人担忧的问题。我们调查了西班牙CPE分离株中RMT的患病率、抗菌药物敏感性、耐药机制、分子流行病学和遗传支持。这项研究包括2018年从32家参与的西班牙医院回收的468株CPE分离株。使用肉汤微量稀释法、琼脂稀释法(磷霉素)或MIC梯度条(普拉佐霉素)测定MIC。所有分离株进行杂交全基因组测序(WGS)。序列类型(ST),核心基因组系统发育相关性,水平获得性耐药机制,质粒分析和RMT的遗传环境,在所有RMT阳性分离株的WGS数据中通过计算机确定。在评价的468株CPE分离株中,从西班牙5个地区的9家不同医院回收的24株分离株(5.1%)对所有氨基糖苷类药物均显示耐药,且RMT呈阳性(21株RmtF、2株阿尔马和1株RmtC)。所有RMT生产者对所有氨基糖苷类抗生素(包括普拉佐霉素)均表现出高水平的耐药性,并且在大多数情况下表现出广泛的耐药敏感性。RMT阳性分离株的遗传多样性较低,是携带bla OXA-48、bla NDM-1或bla Vim-1碳青霉烯酶基因的肺炎克雷伯菌(ST 147、ST 101、ST 395)和阴沟肠杆菌(ST 93)的全球克隆。RMT存在于五种不同的多药耐药质粒中,并与有效的移动的遗传元件相关联。我们的研究结果强调,RMTs正在出现在西班牙的临床CPE分离株中,应监测其传播情况,以保护氨基糖苷类和普拉佐霉素未来的临床效用。(C)2021爱思唯尔有限公司和国际抗菌药物化学治疗学会。All rights reserved.
The emergence of 16S rRNA methyltransferases (RMTs) in Gram-negative pathogens bearing other clinically relevant resistance mechanisms, such as carbapenemase-producing Enterobacterales (CPE), is becoming an alarming concern. We investigated the prevalence, antimicrobial susceptibility, resistance mechanisms, molecular epidemiology and genetic support of RMTs in CPE isolates from Spain. This study included a collection of 468 CPE isolates recovered during 2018 from 32 participating Spanish hospitals. MICs were determined using the broth microdilution method, the agar dilution method (fosfomycin) or MIC gradient strips (plazomicin). All isolates were subjected to hybrid whole-genome sequencing (WGS). Sequence types (STs), core genome phylogenetic relatedness, horizontally acquired resistance mechanisms, plasmid analysis and the genetic environment of RMTs were determined in silico from WGS data in all RMT-positive isolates. Among the 468 CPE isolates evaluated, 24 isolates (5.1%) recovered from nine different hospitals spanning five Spanish regions showed resistance to all aminoglycosides and were positive for an RMT (21 RmtF, 2 ArmA and 1 RmtC). All RMT-producers showed high-level resistance to all aminoglycosides, including plazomicin, and in most cases exhibited an extensively drug-resistant susceptibility profile. The RMT-positive isolates showed low genetic diversity and were global clones of Klebsiella pneumoniae (ST147, ST101, ST395) and Enterobacter cloacae (ST93) bearing bla OXA-48, bla NDM-1 or bla VIM-1 carbapenemase genes. RMTs were harboured in five different multidrug resistance plasmids and linked to efficient mobile genetic elements. Our findings highlight that RMTs are emerging among clinical CPE isolates from Spain and their spread should be monitored to preserve the future clinical utility of aminoglycosides and plazomicin. (C) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.