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马来西亚一家三级医院产超广谱β-内酰胺酶和碳青霉烯酶的铜绿假单胞菌菌株的分子特征分析

Molecular Characterization of Extended-Spectrum Beta Lactamase- and Carbapenemase-Producing Pseudomonas aeruginosa Strains from a Malaysian Tertiary Hospital.

作者信息

Phoon Hannah Y P, Hussin Hazilawati, Hussain Baizurah M, Thong Kwai Lin

机构信息

1 Pathology Department, Ampang Hospital , Ampang, Malaysia .

2 Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur, Malaysia .

出版信息

Microb Drug Resist. 2018 Oct;24(8):1108-1116. doi: 10.1089/mdr.2017.0258. Epub 2018 Feb 13.

DOI:10.1089/mdr.2017.0258
PMID:29437541
Abstract

Pseudomonas aeruginosa infections account for high morbidity and mortality rates worldwide. Increasing resistance toward β-lactams, especially carbapenems, poses a serious therapeutic challenge. However, the multilocus sequence typing (MLST) of extended-spectrum beta lactamase (ESBL)- and carbapenemase-producing clinical P. aeruginosa has not been reported in Malaysia. This study aimed to determine the antibiotic susceptibility profiles, resistance genes, pulsotypes, and sequence types (STs) of clinical P. aeruginosa from a Malaysian tertiary hospital. These characteristics were analyzed by disk diffusion, minimum inhibitory concentration, polymerase chain reaction, pulsed-field gel electrophoresis (PFGE), and MLST for 199 nonreplicate clinical strains. The susceptibility of the strains toward the carbapenems and piperacillin-tazobactam was the lowest (≤90%), while ≥90% of the strains remained susceptible to all other classes of antimicrobial agents tested. The multidrug-resistant strains displayed high level resistance to cephalosporins (48 to ≥256 mg/L) and carbapenems (4-32 mg/L). Eleven strains harbored class 1 integrons containing bla, bla, bla, bla, aacA(6')-Ib, aacA(6')-II, aadA6, and gcuD gene cassettes. Extra-integron genes, bla, bla, bla, and bla, were also found. Overall, the maximum likelihood tree showed concordance in the clustering of strains having the same STs and PFGE clusters. ST708 was the predominant antibiotic-susceptible clone detected from the neonatal intensive care unit. The STs 235, 809, and 1076 clonal clusters consisted of multidrug resistant strains. ST235 is a recognized international high-risk clone. This is the first report of bla and bla ESBL-encoding gene variants and novel STs (STs 2329, 2335, 2337, 2338, 2340, and 2341) of P. aeruginosa in Malaysia.

摘要

铜绿假单胞菌感染在全球范围内导致了较高的发病率和死亡率。对β-内酰胺类药物,尤其是碳青霉烯类药物的耐药性不断增加,这构成了严峻的治疗挑战。然而,马来西亚尚未报道产超广谱β-内酰胺酶(ESBL)和碳青霉烯酶的临床铜绿假单胞菌的多位点序列分型(MLST)情况。本研究旨在确定马来西亚一家三级医院临床分离的铜绿假单胞菌的抗生素敏感性谱、耐药基因、脉冲型和序列类型(STs)。通过纸片扩散法、最低抑菌浓度、聚合酶链反应、脉冲场凝胶电泳(PFGE)和MLST对199株非重复临床菌株进行了这些特征分析。菌株对碳青霉烯类药物和哌拉西林-他唑巴坦的敏感性最低(≤90%),而≥90%的菌株对所有其他测试类别的抗菌药物仍敏感。多重耐药菌株对头孢菌素(48至≥256mg/L)和碳青霉烯类药物(4 - 32mg/L)表现出高水平耐药。11株菌株携带含有bla、bla、bla、bla、aacA(6')-Ib、aacA(6')-II、aadA6和gcuD基因盒的1类整合子。还发现了整合子外基因bla、bla、bla和bla。总体而言,最大似然树显示具有相同STs和PFGE簇的菌株聚类结果一致。ST708是从新生儿重症监护病房检测到的主要抗生素敏感克隆。ST235、809和1076克隆簇由多重耐药菌株组成。ST235是一个公认的国际高危克隆。这是马来西亚首次报道铜绿假单胞菌的bla和bla ESBL编码基因变体以及新的STs(ST2329、2335、2337、2338、2340和2341)。

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