2017 年美国肺炎支原体的阿奇霉素敏感性：监测数据的基因组分析。
Azithromycin susceptibility of in the USA in 2017: a genomic analysis of surveillance data.
机构信息
Laboratory Reference and Research Branch (K M Gernert PhD, S Seby MS, M W Schmerer PhD, J C Thomas IV PhD, C D Pham PhD, B H Raphael PhD, E N Kersh PhD), Surveillance and Data Management Branch (S St Cyr MD, H Weinstock PhD), and Epidemiology and Statistics Branch (K Schlanger PhD), Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA; Oak Ridge Institute for Science and Education Research Participation and Fellowship Program, Oak Ridge, TN, USA (S Seby, J C Thomas IV); Department of Microbiology and Immunology and Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA, USA (W M Shafer PhD); and Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, GA, USA (W M Shafer).
出版信息
Lancet Microbe. 2020 Aug;1(4):e154-e164. doi: 10.1016/S2666-5247(20)30059-8.
BACKGROUND
The number of cases of gonorrhoea in the USA and worldwide caused by is increasing (555 608 reported US cases in 2017, and 87 million cases worldwide in 2016). Many countries report declining in vitro susceptibility of azithromycin, which is a concern because azithromycin and ceftriaxone are the recommended dual treatment in many countries. We aimed to identify strain types associated with decreased susceptibility to azithromycin.
METHODS
We did a genomic analysis of isolates obtained by the US Gonococcal Isolate Surveillance Project. Isolates were whole-genome sequenced based on decreased susceptibility to azithromycin (minimal inhibitory concentration [MIC] ≥2 μg/mL, using agar dilution antibiotic susceptibility testing) and geographical representation. Bioinformatic analyses established genomic diversity, strain population dynamics, and antimicrobial resistance profiles.
FINDINGS
410 isolates were sorted into more than 20 unique phylogenetic clades. One predominant persistent clade (consisting of 97 isolates) included the most isolates with azithromycin MICs of 2 μg/mL or higher (61 of 97 [63%] 59 of 311 [19%]; p<0·0001) and carried a mosaic (multiple transferable resistance) locus (68 of 97 [70%] two of 313 [1%]; p<0·0001). Of the remaining 313 isolates, 57 (18%) had decreased susceptibility to azithromycin (MIC ≥4 μg/mL), which was attributed to 23S rRNA variants (56 of 57 [98%]) and formed phylogenetically diverse clades, showing various levels of clonal expansion.
INTERPRETATION
Reduced azithromycin susceptibility was associated with expanding and persistent clades harbouring two well described resistance mechanisms, mosaic locus and 23S rRNA variants. Understanding the role of recombination, particularly within the locus, on the fitness and expansion of strains with decreased susceptibility has important implications for the public health response to minimise gonorrhoea transmission.
FUNDING
US Centers for Disease Control and Prevention (CDC), CDC Combating Antibiotic Resistant Bacteria initiative, Oak Ridge Institute for Science Education, US Department of Energy/CDC/Emory University, National Institutes of Health, and Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs.
背景
美国和全球的淋病病例数量不断增加，其中 引起的淋病病例数量不断增加（2017 年报告美国有 555608 例病例，2016 年全球有 8700 万例病例）。许多国家报告阿奇霉素体外敏感性下降，这令人担忧，因为阿奇霉素和头孢曲松是许多国家推荐的双重治疗药物。我们旨在确定与阿奇霉素敏感性降低相关的菌株类型。
方法
我们对美国淋球菌分离监测项目获得的 分离株进行了基因组分析。根据阿奇霉素敏感性降低（最低抑菌浓度 [MIC]≥2μg/mL，琼脂稀释抗生素敏感性试验）和地理代表性，对分离株进行全基因组测序。生物信息学分析建立了基因组多样性、菌株种群动态和抗菌药物耐药性特征。
结果
410 株分离株被分为 20 多个独特的系统发育分支。一个主要的持续性分支（由 97 株组成）包括大多数阿奇霉素 MIC 为 2μg/mL 或更高的分离株（97 株中的 61 株 [63%]，311 株中的 59 株 [19%]；p<0.0001），并携带镶嵌 （多重可转移耐药性）基因座（97 株中的 68 株 [70%]，313 株中的 2 株 [1%]；p<0.0001）。在其余 313 株分离株中，57 株（18%）对阿奇霉素的敏感性降低（MIC≥4μg/mL），这归因于 23S rRNA 变体（57 株中的 56 株 [98%]），并形成了具有不同克隆扩张水平的系统发育多样的分支。
结论
阿奇霉素敏感性降低与不断扩大和持续的分支有关，这些分支携带有两种已充分描述的耐药机制，即镶嵌基因座和 23S rRNA 变体。了解重组，特别是在 基因座内，对降低敏感性菌株的适应性和扩张的作用，对减少淋病传播的公共卫生应对具有重要意义。
资助
美国疾病控制与预防中心（CDC），CDC 对抗抗生素耐药细菌倡议，橡树岭科学教育研究所，美国能源部/CDC/埃默里大学，美国国立卫生研究院和美国退伍军人事务部生物医学实验室研究与发展服务。
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