Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000-2013.

Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000-2013.
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DOI:
10.1093/infdis/jiw420
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发表时间:
2016-11-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Lipsitch M
Lipsitch M
中科院分区:
其他
文献类型:
--
作者:
Grad YH;Harris SR;Kirkcaldy RD;Green AG;Marks DS;Bentley SD;Trees D;Lipsitch M

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背景。 淋病奈瑟菌感染的治疗是经验性的,并且基于人群的易感性。不断增加的抗菌药物耐药性强调了快速诊断测试(包括基于序列的测试)对指导治疗的潜在重要性。然而,基于序列的诊断测试的有用性取决于耐药机制的普遍性和动态。方法。 我们确定了 2000 年至 2013 年通过疾病控制和预防中心淋球菌分离株监测项目收集的 1102 株耐药和易感临床淋病奈瑟菌分离株中超广谱头孢菌素、大环内酯类和氟喹诺酮类药物的耐药标记物的流行率和动态。结果。 广谱头孢菌素敏感性降低主要是克隆性的,与镶嵌 penA XXXIV 等位基因和衍生物有关(头孢克肟的敏感性为 98%,头孢曲松的敏感性为 91%),但零星出现了替代耐药机制。阿奇霉素敏感性降低是通过多种机制引起的,并且显示出有限的克隆传播; 36% 对阿奇霉素敏感性降低的分离株产生耐药性的基础尚不清楚。耐喹诺酮类淋病奈瑟菌已多次出现,并具有广泛的克隆传播。结论。 喹诺酮耐药性淋病奈瑟菌和头孢克肟敏感性降低似乎适合开发基于序列的诊断测试,而头孢曲松和阿奇霉素的未明确耐药机制强调了表型监测的重要性。多重耐药菌株的鉴定凸显了采取额外措施应对无法治疗的淋病威胁的必要性。
Background. Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms. Methods. We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project. Results. Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread. Conclusions. Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea.
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