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巴西里约热内卢临床分离铜绿假单胞菌的流行病学和抗生素耐药趋势:多年来(1995-2015 年)突变机制的重要性。

Epidemiology and antibiotic resistance trends in clinical isolates of Pseudomonas aeruginosa from Rio de janeiro - Brazil: Importance of mutational mechanisms over the years (1995-2015).

机构信息

Laboratório de Pesquisa em Infecção Hospitalar, Oswaldo Cruz Institute, Fiocruz, Brasil Avenue 4365, Manguinhos, 21040-360, Rio de Janeiro, Rio de Janeiro, Brazil.

Laboratório de Pesquisa em Infecção Hospitalar, Oswaldo Cruz Institute, Fiocruz, Brasil Avenue 4365, Manguinhos, 21040-360, Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Infect Genet Evol. 2019 Sep;73:411-415. doi: 10.1016/j.meegid.2019.05.015. Epub 2019 May 20.

DOI:10.1016/j.meegid.2019.05.015
PMID:31121306
Abstract

Pseudomonas aeruginosa is a major health concern globally and treating infections caused by MDR-isolates unarguably a humongous challenge that remains an unmet need in modern medicine. To determine patterns and mechanisms of antimicrobial resistance and its spread over the years in Rio de Janeiro, Brazil, 88 P. aeruginosa isolates were selected from 1995 to 2015. Phenotypic and genotypic characterization of antimicrobial resistance was evaluated and isolates were submitted to clonality by PFGE and MLST. PFGE analysis showed a great variability of clonal groups mainly over the past 10 years of this study. STs predominant in the early years (ST804, ST1860, ST487 and ST1602) associated to multidrug resistance (MDR) phenotype were replaced by ST277, ST244, ST1945, ST1791 with extensive drug resistance (XDR) in last years, with significant increase in resistance to carbapenems, fluoroquinolones and aminoglycosides. Colistin resistance was detected in 3.5%. The main mechanisms of antimicrobial resistance were mutational mechanisms (mutations in oprD, mexT and gyrA genes). We found the ESBL genes bla (n = 2), bla (n = 3) and bla (n = 1).The carbapenemases genes was present in ST277 (bla, n = 3), ST1560 (bla, n = 3) and ST1944 (bla, n = 2). The 16S RNA methylase gene (rmtD) was found in five isolates belonged to ST277. In conclusion, molecular epidemiological investigation reveals an increase of antimicrobial resistance in P. aeruginosa over 21 years in Rio de Janeiro with higher population structure and occurrence of high risk clone in the last years. The mutational mechanisms of resistance were present in all XDR isolates.

摘要

铜绿假单胞菌是全球范围内的一个主要健康关注点,治疗耐多药分离株引起的感染无疑是现代医学尚未满足的巨大挑战。为了确定巴西里约热内卢多年来抗菌药物耐药性的模式和机制及其传播情况,我们从 1995 年至 2015 年选择了 88 株铜绿假单胞菌分离株。评估了抗菌药物耐药表型和基因型特征,并通过 PFGE 和 MLST 对分离株进行了克隆性分析。PFGE 分析显示,主要是在本研究过去 10 年中,克隆群存在很大的变异性。在早期主要流行的 STs(ST804、ST1860、ST487 和 ST1602)与多药耐药(MDR)表型相关,而在最近几年则被 ST277、ST244、ST1945、ST1791 取代,这些菌株具有广泛的耐药性(XDR),对碳青霉烯类、氟喹诺酮类和氨基糖苷类药物的耐药性显著增加。检测到 3.5%的粘菌素耐药。抗菌药物耐药的主要机制是突变机制(oprD、mexT 和 gyrA 基因的突变)。我们发现了 ESBL 基因 bla(n=2)、bla(n=3)和 bla(n=1)。在 ST277(bla,n=3)、ST1560(bla,n=3)和 ST1944(bla,n=2)中发现了碳青霉烯酶基因。在五个属于 ST277 的分离株中发现了 16S RNA 甲基化酶基因(rmtD)。总之,分子流行病学调查显示,在过去 21 年里,里约热内卢的铜绿假单胞菌的抗菌药物耐药性有所增加,其人群结构更高,最后几年出现了高风险克隆。所有 XDR 分离株均存在耐药突变机制。

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