背景。幽门螺杆菌（幽门螺杆菌）是影响世界近一半人口的最常见和持续的细菌感染之一。抗生素耐药性是一个不断发展的过程，需要对抗生素耐药性进行局部监测，以指导临床医生选择治疗方案。本研究的目的是建立一种基于微阵列的检测方法，以鉴定幽门螺杆菌感染，克拉霉素和左氧氟沙星的易感性，以及CYP2C19基因多态性和质子泵抑制剂（PPI）的潜在选择指南，针对特定幽门螺杆菌根除的抗生素管理治疗。方法。通过分析人类基因组CYP2C19⁎2和CYP2C19⁎3的序列以及分别赋予克拉霉素和左氧氟沙星抗性的23S rRNA和gyrA基因区域内的突变，我们开发了一种用于个体治疗检测幽门螺杆菌感染的微阵列。建立质粒作为阳性或检测限（LOD）参考材料。已经进行了微阵列的特异性和灵敏度。并且测试了总共1083个胃活组织检查样品，并且在阵列和Sanger测序之间计算了Kappa值。我们还分析了中国对克拉霉素和左氧氟沙星的耐药性，以及CYP2C19基因多态性。结果。检测幽门螺杆菌的LOD为103CFU / mL，人基因组DNA为2ng /μL。 1083例胃活检标本检测结果显示幽门螺旋杆菌阳性691例（63.80％），克拉霉素耐药266例（38.49％），左氧氟沙星耐药192例（27.79％），其中61例（8.83％）对两者都有抵抗力。对于CYP2C19多态性的类型，412（38.04％）是纯合快速型（HomEM），574（53％）是杂合EM（HetEM），97（8.96％）是弱代谢者（PM）。结论。所提出的基于微阵列的检测具有高特异性，灵敏度和重现性，可用于检测克拉霉素或左氧氟沙星以及CYP2C19多态性的耐药性，这可能有助于提高幽门螺杆菌的临床根除率。

Background. Helicobacter pylori (H. pylori) is one of the most frequent and persistent bacterial infections that affect nearly half of the world's population. Antibiotic resistance is a constantly evolving process and local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. The aim of this study was to establish a microarray-based detection to identify H. pylori infection, clarithromycin and levofloxacin susceptibility, and CYP2C19 genetic polymorphism and guide to potential choice of proton pump inhibitor (PPI), antibiotic administration for tailored H. pylori eradication therapy. Methods. By analyzing the sequence of human genomic CYP2C19⁎2 and CYP2C19⁎3 and mutations within the 23S rRNA and gyrA gene regions conferring clarithromycin and levofloxacin resistance, respectively, we developed a microarray for individual therapy detection of H. pylori infection. Plasmids were established as positive or limit of detection (LOD) reference materials. The specificity and sensitivity of the microarray had been performed. And a total of 1083 gastric biopsy samples were tested and the Kappa value had been calculated between the array and Sanger sequencing. We also analyzed the resistance to clarithromycin and levofloxacin in China, as well as the CYP2C19 polymorphisms. Results. The LOD of detecting H. pylori was 103 CFU/mL and human genome DNA was 2 ng/μL. The detection results of 1083 gastric biopsy samples showed that 691 (63.80%) were H. pylori positive, of which 266 (38.49%) were resistant to clarithromycin, 192 (27.79%) were resistant to levofloxacin, and 61 (8.83%) were resistant to both of them. For the type of CYP2C19 polymorphism, 412 (38.04%) were homozygous fast type (HomEM), 574 (53%) were heterozygous EM (HetEM), and 97 (8.96%) were poor metabolizer (PM). Conclusions. The proposed microarray-based detection has high specificity, sensitivity, and reproducibility for detecting the resistance of clarithromycin or levofloxacin as well as CYP2C19 polymorphism, which may help to improve the clinical eradication rate of H. pylori.

https://www.ncbi.nlm.nih.gov/pubmed/30276203