Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study.
Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study.
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DOI：
10.1016/s1473-3099(13)70693-5
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发表时间：
2014-03
影响因子：
56.3
通讯作者：
Lipsitch, Marc
中科院分区：
文献类型：
--
作者：
Grad, Yonatan H.;Kirkcaldy, Robert D.;Trees, David;Dordel, Janina;Harris, Simon R.;Goldstein, Edward;Weinstock, Hillard;Parkhill, Julian;Hanage, William P.;Bentley, Stephen;Lipsitch, Marc
淋病奈瑟菌对超广谱头孢菌素敏感性降低的出现提高了无法治疗的淋病的前景。在缺乏新的治疗方法的情况下，努力减缓耐药淋球菌发病率的增加需要深入了解导致其出现和传播的因素。我们评估了美国分离株之间的相关性，并通过不同的性网络重建了可能的谱系传播。我们对美国疾病控制和预防中心的淋球菌分离株监测项目（GISP）从美国定点公共性传播疾病诊所收集的236株淋球菌分离株的基因组进行了测序，包括2009-10年GISP中对头孢克肟（cefRS）敏感性降低的118株（97%）和118株头孢克肟-来自GISP的敏感分离株尽可能通过地点、采集日期和性取向匹配。我们评估了抗菌素耐药基因型和表型之间的关联，以及与位置和性取向相关的系统发育聚类。镶嵌型佩纳XXXIV对cefRS具有较高的阳性预测值。我们发现118株头孢RS分离株中有2株缺乏嵌合型佩纳等位基因，复检显示这2株对头孢克肟敏感。在剩余的116株cefRS分离株中，114株（98%）属于两个不同的谱系，其具有独立获得的嵌合佩纳等位基因XXXIV。cefRS菌株的一个主要谱系向东传播，主要是通过与男性发生性关系的男性的性网络。九个推断的性网络之间的转变中有八个是从与男性发生性关系的男性介绍到异性恋人群。基因组学方法可能有助于通过加强淋球菌爆发监测和识别可能受益于增加对淋病奈瑟菌感染的筛查的人群来减缓耐药淋病奈瑟菌的传播。美国性传播疾病协会、惠康信托基金会、国家普通医学科学研究所、国家过敏和传染病研究所、国家卫生研究院。
The emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spectrum cephalosporins raises the prospect of untreatable gonorrhoea. In the absence of new treatments, efforts to slow the increasing incidence of resistant gonococcus require insight into the factors that contribute to its emergence and spread. We assessed the relatedness between isolates in the USA and reconstructed likely spread of lineages through different sexual networks. We sequenced the genomes of 236 isolates of N gonorrhoeae collected by the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project (GISP) from sentinel public sexually transmitted disease clinics in the USA, including 118 (97%) of the isolates from 2009–10 in GISP with reduced susceptibility to cefixime (cefRS) and 118 cefixime-susceptible isolates from GISP matched as closely as possible by location, collection date, and sexual orientation. We assessed the association between antimicrobial resistance genotype and phenotype and correlated phylogenetic clustering with location and sexual orientation. Mosaic penA XXXIV had a high positive predictive value for cefRS. We found that two of the 118 cefRS isolates lacked a mosaic penA allele, and rechecking showed that these two were susceptible to cefixime. Of the 116 remaining cefRS isolates, 114 (98%) fell into two distinct lineages that have independently acquired mosaic penA allele XXXIV. A major lineage of cefRS strains spread eastward, predominantly through a sexual network of men who have sex with men. Eight of nine inferred transitions between sexual networks were introductions from men who have sex with men into the heterosexual population. Genomic methods might aid efforts to slow the spread of antibiotic-resistant N gonorrhoeae through augmentation of gonococcal outbreak surveillance and identification of populations that could benefit from increased screening for aymptomatic infections. American Sexually Transmitted Disease Association, Wellcome Trust, National Institute of General Medical Sciences, and National Institute of Allergy and Infectious Diseases, National Institutes of Health.