David Geffen School of Medicine at UCLAgrid.471398.0, Los Angeles, California, USA.
Division of Infectious Diseases, David Geffen School of Medicine at UCLAgrid.471398.0, Los Angeles, California, USA.
Microbiol Spectr. 2022 Apr 27;10(2):e0206521. doi: 10.1128/spectrum.02065-21. Epub 2022 Mar 29.
Antimicrobial resistance in N. gonorrhoeae is increasing globally, and ceftriaxone is the recommended treatment for empirical therapy in most settings. Developing molecular assays to detect decreased ceftriaxone susceptibility is critical. Using PathogenWatch, a public database of N. gonorrhoeae genomes, antibiotic susceptibility data and DNA sequences of different genes associated with ceftriaxone resistance were extracted. That information was used to determine the sensitivity and specificity of different molecular markers and algorithms to predict decreased susceptibility to ceftriaxone. A total of 12,943 N. gonorrhoeae genomes were extracted from the PathogenWatch database, of which 9,540 genomes were used in the analysis. The sensitivity and specificity of specific molecular markers and algorithms were largely consistent with prior reports. Small variation (<10%) in either sensitivity or specificity occurred. Certain algorithms using different molecular markers at various prevalence of decreased ceftriaxone susceptibility identified a potentially clinically useful range of positive and negative predictive values. We validated previously described mutations and algorithms in a large public database containing a global collection of N. gonorrhoeae genomes. Certain mutations and algorithms resulted in sensitivity and specificity values consistent with those of prior studies. Further research is needed to integrate these markers and algorithms into the development of molecular assays to predict decreased ceftriaxone susceptibility. Antimicrobial resistance in Neisseria gonorrhoeae (N. gonorrhoeae), the causative agent of gonorrhea, is rising globally. Ceftriaxone is the last remaining antibiotic for empirical treatment of gonorrhea. Developing molecular tests to predict ceftriaxone resistance can help to improve detection and surveillance of ceftriaxone resistance. Here, we utilized PathogenWatch, a public global online database of N. gonorrhoeae genomes, to evaluate different genetic markers in predicting decreased susceptibility to ceftriaxone. We compiled MICs for ceftriaxone from the PathogenWatch database and used a computational approach to extract all the genetic markers from the genomic data. We determined the sensitivity and specificity for predicting decreased ceftriaxone susceptibility among several combinations of genetic markers. We identified several combinations of genetic markers with high predictive values for decreased susceptibility to ceftriaxone. These combinations of genetic markers might be promising candidates for future molecular tests to predict ceftriaxone resistance.
淋病奈瑟菌（Neisseria gonorrhoeae）的耐药性在全球范围内不断增加，头孢曲松已被推荐为大多数情况下经验性治疗的首选药物。开发检测头孢曲松敏感性降低的分子检测方法至关重要。
本研究使用公共数据库 PathogenWatch 提取淋病奈瑟菌基因组、抗生素药敏数据和与头孢曲松耐药相关的不同基因的 DNA 序列。利用这些信息确定不同分子标记物和算法预测头孢曲松敏感性降低的灵敏度和特异性。
从 PathogenWatch 数据库中提取了 12943 个淋病奈瑟菌基因组，其中 9540 个基因组用于分析。特定分子标记物和算法的灵敏度和特异性与先前的报告基本一致。灵敏度或特异性的小变化（<10%）。在头孢曲松敏感性降低的不同流行率下使用不同分子标记物的某些算法确定了具有潜在临床意义的阳性和阴性预测值范围。
我们在一个包含全球淋病奈瑟菌基因组的大型公共数据库中验证了先前描述的突变和算法。某些突变和算法导致的灵敏度和特异性值与先前研究一致。需要进一步的研究将这些标记物和算法整合到预测头孢曲松敏感性降低的分子检测中。
淋病奈瑟菌（Neisseria gonorrhoeae，简称淋球菌）是淋病的病原体，其耐药性在全球范围内不断上升。头孢曲松是治疗淋病的最后一种经验性抗生素。开发预测头孢曲松耐药性的分子检测方法有助于提高对头孢曲松耐药性的检测和监测。
在这里，我们利用公共全球淋病奈瑟菌基因组数据库 PathogenWatch 来评估不同的遗传标记物在预测头孢曲松敏感性降低方面的作用。我们从 PathogenWatch 数据库中编译了头孢曲松的 MIC 值，并使用计算方法从基因组数据中提取了所有的遗传标记物。我们确定了几种遗传标记物组合预测头孢曲松敏感性降低的灵敏度和特异性。
我们发现了一些对头孢曲松敏感性降低具有高预测值的遗传标记物组合。这些遗传标记物组合可能是未来预测头孢曲松耐药性的分子检测的有前途的候选物。
