中国耐头孢曲松淋病奈瑟菌 FC428 克隆的持续传播。

Sustained transmission of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in China.

机构信息

Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.

National Center for Sexually Transmitted Disease Control, China Center for Disease Control and Prevention, Nanjing, China.

出版信息

J Antimicrob Chemother. 2020 Sep 1;75(9):2499-2502. doi: 10.1093/jac/dkaa196.

DOI:10.1093/jac/dkaa196

PMID:32473014

Abstract

BACKGROUND

Ceftriaxone resistance in Neisseria gonorrhoeae has become an imminent threat to effective control of gonorrhoea globally. In recent years, the ceftriaxone-resistant FC428 clone has shown international dissemination. After our first report of the FC428 clone in China in 2016, we now describe another six cases of FC428-related ceftriaxone-resistant N. gonorrhoeae isolates from 2017 and 2018.

OBJECTIVES

To identify the phenotypic and molecular characteristics of newly reported ceftriaxone-resistant isolates in China and to investigate the relationship between these isolates and FC428 clones reported globally.

METHODS

Antimicrobial susceptibility to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, ciprofloxacin and tetracycline was determined by the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed for genotyping and SNPs extracted from whole-genome sequences were used for phylogenetic analysis.

RESULTS

All isolates were resistant to ceftriaxone, cefixime, penicillin, tetracycline and ciprofloxacin, but were susceptible to azithromycin and spectinomycin. NG-MAST, MLST and NG-STAR genotyping showed that all isolates shared identical or similar STs (<10 bp difference) to FC428 (NG-MAST ST3435, MLST ST1903, NG-STAR ST233) and contained the same mosaic penA allele 60.001. Phylogenetic analysis showed the Chinese isolates spreading in the whole phylogenetic tree and fully mixed with other international isolates. Half of the Chinese isolates were more closely related (<100 SNPs) to Japanese isolates than other international isolates.

CONCLUSIONS

The newly reported cases in China were related to the internationally spreading FC428 clone. These isolates might have played a central role in international transmission of the FC428 clone. High ceftriaxone doses (1-2 g) still provide effective therapy.

摘要

背景

淋病奈瑟菌对头孢曲松的耐药性已成为全球有效控制淋病的紧迫威胁。近年来，头孢曲松耐药的 FC428 克隆已显示出国际传播。在 2016 年我们首次在中国报告 FC428 克隆后，我们现在描述了 2017 年和 2018 年来自六个不同地区的 6 例与 FC428 相关的头孢曲松耐药淋病奈瑟菌分离株。

目的

鉴定中国新报告的头孢曲松耐药分离株的表型和分子特征，并研究这些分离株与全球报告的 FC428 克隆之间的关系。

方法

采用琼脂稀释法测定头孢曲松、头孢克肟、阿奇霉素、壮观霉素、青霉素、环丙沙星和四环素的药敏性。对淋病奈瑟菌多位点序列分型（NG-MAST）、多位点序列分型（MLST）和淋病奈瑟菌耐药序列分型（NG-STAR）进行基因分型，并从全基因组序列中提取 SNP 进行系统发育分析。

结果

所有分离株均对头孢曲松、头孢克肟、青霉素、四环素和环丙沙星耐药，但对阿奇霉素和壮观霉素敏感。NG-MAST、MLST 和 NG-STAR 基因分型显示，所有分离株的 ST 型（相差<10bp）与 FC428 相同或相似（NG-MAST ST3435、MLST ST1903、NG-STAR ST233），并含有相同的马赛克 penA 等位基因 60.001。系统发育分析显示，中国分离株在整个系统发育树中传播，并与其他国际分离株完全混合。中国分离株中有一半与日本分离株的亲缘关系更近（<100 SNPs），而与其他国际分离株的亲缘关系较远。