新加坡NDM和NDM/ oxa48样双碳青霉烯酶产肠杆菌的氨曲南-阿维巴坦耐药率及耐药机制

IF 3.6 3区 医学 Q1 PATHOLOGY
Ka Lip Chew, Joey Cruz Cabang, Nur Aisyah Binte Abu Bakar, Ker Xin Tan, Jeanette Teo
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引用次数: 0

摘要

Aztreonam-avibactam是金属β-内酰胺酶-碳青霉烯酶产肠杆菌(CPE)的治疗选择。本研究旨在确定CPE对阿唑仑-阿维巴坦的耐药率,并确定相关的耐药机制。采用MIC试纸(MTS)和微稀释(Sensititre)两种方法测定新德里金属β-内酰胺酶(NDM)和NDM/ oxa -48样双cpe分离株的最低抑菌浓度(MIC)。还进行了全基因组测序以进行分子表征。共纳入46例患者的44株NDM- cpe和11株NDM/OXA-48双cpe。纳入的菌株种类分类如下:大肠埃希菌(33株)、肺炎克雷伯菌(12株)、氧化克雷伯菌(1株)、阴沟肠杆菌复合菌(2株)、单胞柠檬酸杆菌(2株)、农柠檬酸杆菌(1株)、弗氏柠檬酸杆菌(1株)、雷氏普罗维登斯菌(2株)、加州Pantoea(1株)。两种检测方法的基本一致性为96.4%,绝对一致性为100%。排除重复菌株后,总耐药率为13.7%。值得注意的是,耐药性仅发生在大肠杆菌和鞭毛虫分离株中。大肠杆菌耐药率为18.8%(6/32,所有菌株),NDM- cpe耐药率为8.0% (2/25),NDM/OXA-48双cpe耐药率为57.1%(4/7)。所有耐药菌株均发现与CMY (ampc型)β-内酰胺酶相关的青霉素结合蛋白3 (PBP3)插入;77.8%(7/9)的菌株mic升高至0.5 ~ 4 mg/L,但仍在敏感断点内,同时存在PBP3插入或AmpC β-内酰胺酶。6株耐阿唑南-阿维巴坦大肠杆菌包括4株ST361和2株ST167。所有三个ST361 NDM/ oxa -48样双cpe分离株均有0-5个单核苷酸多态性。大肠杆菌和普罗维登西亚菌株对氨曲南-阿维巴坦耐药。大肠杆菌的耐药是由与AmpC产生相关的PBP3突变驱动的。由ST361分离株驱动的ndm - oxa -48样双碳青霉烯酶产生大肠杆菌的耐药率较高。阿曲南-阿维巴坦药敏试验应作为侵袭性NDM-CPE感染常规诊断检测的一部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Aztreonam-avibactam resistance rates and resistance mechanisms of NDM and NDM/OXA48-like dual-carbapenemase-producing Enterobacterales in Singapore.

Aztreonam-avibactam is a treatment option for metallo-β-lactamase carbapenemase-producing Enterobacterales (CPE). This study was performed to determine resistance rates of a collection of CPE against aztreonam-avibactam and characterise associated resistance mechanisms. Minimum inhibitory concentrations (MICs) of a collection of New Delhi metallo-β-lactamase (NDM)- and NDM/OXA-48-like dual-CPE isolates were determined using two methods, the MIC Test Strip (MTS) and broth microdilution (Sensititre). Whole-genome sequencing was also performed for molecular characterisation. A total of 44 NDM-CPE and 11 NDM/OXA-48 dual-CPE isolates from 46 patients were included. The species breakdown of included isolates was as follows: Escherichia coli (n=33), Klebsiella pneumoniae (n=12), Klebsiella oxytoca (n=1), Enterobacter cloacae complex (n=2), Citrobacter amalonaticus (n=2), Citrobacter farmeri (n=1), Citrobacter freundii (n=1), Providencia rettgeri (n=2), and Pantoea calida (n=1). Essential agreement between the two test methods was 96.4%, with 100% categorical agreement. Overall resistance was 13.7% after excluding duplicate isolates. Of note, resistance occurred only in E. coli and P. rettgeri isolates. Resistance rates in E. coli isolates were 18.8% (6/32, all isolates), 8.0% (2/25) for NDM-CPE, and 57.1% (4/7) for NDM/OXA-48 dual-CPE. All resistant isolates were found to have penicillin-binding protein 3 (PBP3) insertions in association with CMY (AmpC-type) β-lactamase; 77.8% (7/9) of E. coli isolates with increased MICs of 0.5-4 mg/L, but still within susceptible breakpoints, also had either PBP3 insertion or AmpC β-lactamase. The six aztreonam-avibactam-resistant E. coli consisted of four ST361 and two ST167 isolates. All three ST361 NDM/OXA-48-like dual-CPE isolates had 0-5 single-nucleotide polymorphisms. Aztreonam-avibactam resistance was detected in E. coli and Providencia spp. Resistance in E. coli isolates was driven by PBP3 mutations in association with AmpC production. Higher resistance rates were seen in NDM-OXA-48-like dual-carbapenemase-producing E. coli, driven by ST361 isolates. Aztreonam-avibactam susceptibility testing should be performed as part of routine diagnostic testing for invasive NDM-CPE infections.

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来源期刊
Pathology
Pathology 医学-病理学
CiteScore
6.50
自引率
2.20%
发文量
459
审稿时长
54 days
期刊介绍: Published by Elsevier from 2016 Pathology is the official journal of the Royal College of Pathologists of Australasia (RCPA). It is committed to publishing peer-reviewed, original articles related to the science of pathology in its broadest sense, including anatomical pathology, chemical pathology and biochemistry, cytopathology, experimental pathology, forensic pathology and morbid anatomy, genetics, haematology, immunology and immunopathology, microbiology and molecular pathology.
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