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加拿大安大略省淋病奈瑟菌分离株中抗菌药物耐药机制的分子分析。

Molecular analysis of antimicrobial resistance mechanisms in Neisseria gonorrhoeae isolates from Ontario, Canada.

机构信息

Ontario Agency for Health Protection and Promotion, Public Health Laboratory, Toronto, ON, Canada.

出版信息

Antimicrob Agents Chemother. 2011 Feb;55(2):703-12. doi: 10.1128/AAC.00788-10. Epub 2010 Nov 22.

Abstract

Surveillance of gonococcal antimicrobial resistance and the molecular characterization of the mechanisms underlying these resistance phenotypes are essential in order to establish correct empirical therapies, as well as to describe the emergence of new mechanisms in local bacterial populations. To address these goals, 149 isolates were collected over a 1-month period (October-November 2008) at the Ontario Public Health Laboratory, Toronto, Canada, and susceptibility profiles (8 antibiotics) were examined. Mutations in previously identified targets or the presence of some enzymes related to resistance (r), nonsusceptibility (ns) (resistant plus intermediate categories), or reduced susceptibility (rs) to the antibiotics tested were also studied. A significant proportion of nonsusceptibility to penicillin (PEN) (89.2%), tetracycline (TET) (72.3%), ciprofloxacin (CIP) (29%), and macrolides (erythromycin [ERY] and azithromycin; 22.3%) was found in these strains. Multidrug resistance was observed in 18.8% of the collection. Although all the strains were susceptible to spectinomycin and extended-spectrum cephalosporins (ESC) (ceftriaxone and cefixime), 9.4% of them displayed reduced susceptibility to extended-spectrum cephalosporins. PBP 2 mosaic structures were found in all of these ESC(rs) isolates. Alterations in the mtrR promoter, MtrR repressor (TET(r), PEN(ns), ESC(rs), and ERY(ns)), porin PIB (TET(r) and PEN(ns)), and ribosomal protein S10 (TET(r)) and double mutations in gyrA and parC quinolone resistance-determining regions (QRDRs) (CIP(r)) were associated with and presumably responsible for the resistance phenotypes observed. This is the first description of ESC(rs) in Canada. The detection of this phenotype indicates a change in the epidemiology of this resistance and highlights the importance of continued surveillance to preserve the last antimicrobial options available.

摘要

监测淋病奈瑟菌的抗菌药物耐药性,并对这些耐药表型背后的机制进行分子特征分析,对于确定正确的经验性治疗方案以及描述当地细菌群体中新机制的出现至关重要。为了实现这些目标,我们在加拿大安大略省公共卫生实验室收集了 149 株分离株,采集时间为 1 个月(2008 年 10 月至 11 月),并检测了药敏谱(8 种抗生素)。我们还研究了先前确定的靶标突变以及一些与耐药(r)、非敏感性(ns)(耐药和中介类别)或对测试抗生素的敏感性降低(rs)相关的酶的存在。这些菌株对青霉素(PEN)(89.2%)、四环素(TET)(72.3%)、环丙沙星(CIP)(29%)和大环内酯类(红霉素[ERY]和阿奇霉素;22.3%)的非敏感性比例较高。在该采集物中观察到 18.8%的多重耐药性。尽管所有菌株均对大观霉素和扩展谱头孢菌素(ESC)(头孢曲松和头孢克肟)敏感,但其中 9.4%对 ESC 表现出敏感性降低。在所有这些 ESC(rs)分离株中均发现 PBP2 马赛克结构。mtrR 启动子、MtrR 阻遏物(TET(r)、PEN(ns)、ESC(rs)和 ERY(ns))、孔蛋白 PIB(TET(r)和 PEN(ns))和核糖体蛋白 S10(TET(r))的改变以及 gyrA 和 parC 喹诺酮耐药决定区(QRDRs)(CIP(r))的双突变与观察到的耐药表型有关,可能是导致这些表型的原因。这是加拿大首次描述 ESC(rs)。该表型的检测表明该耐药性的流行病学发生了变化,突显了持续监测以保留现有最后抗菌药物选择的重要性。

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