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2013-14 年期间法国分离的耐阿奇霉素淋病奈瑟菌的分子流行病学和耐药机制。

Molecular epidemiology and mechanisms of resistance of azithromycin-resistant Neisseria gonorrhoeae isolated in France during 2013-14.

机构信息

APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France Department of Tropical and Infectious Diseases, CHI, Villeneuve Saint Georges, France.

APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.

出版信息

J Antimicrob Chemother. 2016 Sep;71(9):2471-8. doi: 10.1093/jac/dkw182. Epub 2016 Jun 14.

Abstract

OBJECTIVES

The objective of this study was to determine the prevalence and mechanisms of azithromycin resistance of Neisseria gonorrhoeae French isolates from 2013 to 2014.

METHODS

N. gonorrhoeae samples isolated in a network of laboratories were tested for susceptibility to azithromycin between April 2013 and March 2014. Fifty-four isolates that were non-susceptible to azithromycin and 18 susceptible isolates were characterized for molecular mechanisms of resistance by PCR/sequencing and genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST).

RESULTS

Among the 970 N. gonorrhoeae isolates, 54 (5.56%) were non-susceptible to azithromycin, 9 (1%) were resistant and 45 (4.6%) showed intermediate resistance. Azithromycin-non-susceptible isolates harboured a C2599T mutation in the rrl gene encoding the 23S rRNA alleles (5.5%), a C substitution in the mtrR promoter (5.5%), an A deletion in the mtrR promoter (53.7%) and mutations in the L4 ribosomal protein (14.8%) and in the MtrR repressor (25.9%). No isolates showed an L22 mutation or carried an erm, ere, mef(A)/(E) or mphA gene. Thirty different STs were highlighted using the NG-MAST technique. The predominant genogroups non-susceptible to azithromycin were G21 (31%), G1407 (20%) and G2400 (15%). Genogroup G2400 (15%) was revealed to be a novel cluster prevalent in the south of France and resistant to azithromycin, ciprofloxacin and tetracycline.

CONCLUSIONS

Our study highlights that the prevalence of resistance of N. gonorrhoeae to azithromycin in France is low and essentially due to multiple genetic mutations. Its dissemination occurs through three major genogroups including a novel one in France (G2400).

摘要

目的

本研究旨在确定 2013 年至 2014 年法国淋病奈瑟菌分离株对阿奇霉素的耐药率及其机制。

方法

2013 年 4 月至 2014 年 3 月,在一个实验室网络中对淋病奈瑟菌分离株进行了阿奇霉素药敏试验。对 54 株非敏感株和 18 株敏感株进行了耐药分子机制的检测,采用 PCR/测序和 N. gonorrhoeae 多抗原序列分型(NG-MAST)进行了基因分型。

结果

在 970 株淋病奈瑟菌分离株中,54 株(5.56%)对阿奇霉素不敏感,9 株(1%)耐药,45 株(4.6%)呈中度耐药。阿奇霉素不敏感株 rrl 基因编码 23S rRNA 等位基因(5.5%)的 C2599T 突变、mtrR 启动子的 C 取代(5.5%)、mtrR 启动子的 A 缺失(53.7%)、L4 核糖体蛋白(14.8%)和 MtrR 阻遏物(25.9%)突变。未发现携带 erm、ere、mef(A)/(E) 或 mphA 基因的菌株。使用 NG-MAST 技术发现了 30 种不同的 ST。对阿奇霉素不敏感的主要基因群为 G21(31%)、G1407(20%)和 G2400(15%)。发现基因群 G2400(15%)是法国南部流行的一种新的耐药簇,对阿奇霉素、环丙沙星和四环素均耐药。

结论

本研究表明,法国淋病奈瑟菌对阿奇霉素的耐药率较低,主要与多种基因突变有关。其传播主要通过三个主要基因群,包括法国的一个新基因群(G2400)。

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