湖州地区幽门螺杆菌对克拉霉素和左氧氟沙星的耐药情况及耐药基因突变位点分析

Prevalence of the resistance to clarithromycin and levofloxacin, and related gene mutations in Helicobacter pylori in Huzhou area

目的：研究湖州地区幽门螺杆菌（Hp）对克拉霉素和左氧氟沙星的耐药性及与相关基因突变的情况，为临床根除Hp提供依据。方法收集湖州市中心医院267例胃炎、胃溃疡及胃癌患者的胃黏膜样本，并成功分离136株Hp，采用平板掺入法检测Hp对克拉霉素和左氧氟沙星的耐药性；提取基因组DNA，采用基因芯片法针对23S rRNA V区（可变区）的2142位点和2143位点及gyrA基因QRDR区（含喹诺酮类耐药决定区）的87位点和91位点进行基因突变的检测。结果136株Hp中对克拉霉素和左氧氟沙星的耐药率分别为7.35%（10/136）和17.65%（24/136）；基因芯片结果检测出2143位点突变17例，2142位点未发生突变；同时也检测出gyrA基因突变27例，其中87位点突变25例，91位点突变2例。结论湖州地区Hp对克拉霉素耐药率不高，突变位点主要为2143位点，宜将克拉霉素继续作为一线药物使用；对左氧氟沙星耐药率高，gyrA基因突变的位点以87位点为主，建议临床用药依据药敏试验结果。

Objective To analyze the resistance to clarithromycin and levofloxacin by Helicobacter pylori （Hp） strains, and explore the related gene mutation, in order to provide evidence for clinical treatment of eradicating Hp. Methods There were 136 Hp strains isolated from gastric mucosa biopsy specimens collected from 267 gastritis patients in Huzhou Central Hospital. Plate incorporation method was used to determine clarithromycin and levofloxacin resistance. Hp genomic DNA was extracted, and the gene mutation of 2 142 and 2 143 gene loci in the V Region （variable region） of 23S rRNA, as well as the 87 and 91 gene loci in the QRDR Region （Quinolone Resistence Determining Region） of gene gyrA were detected by gene chips. Results There were 10（7.35%） and 24（17.65%） strains found resistant to clarithromycin and levofloxacin in 136 strains, respectively. The detection result of using gene chips indicated that 17 strains in 2 143 gene loci mutated while no strain mutated in 2 142 gene loci of 23S rRNA. At the same time, 27 strains gyrA gene mutated, including 25 strains in 87 gene loci and 2 strains in 91 gene loci . Conclusions The prevalence of Hp resistance to clarithromycin is not high in Huzhou, and the 2 143 gene loci mutation is the main gene mutation, so clarithromycin could still be the first-line antibiotics for Hp treatment. However, the prevalence of Hp resistance to levofloxacin is high in Huzhou, and the 87 gene loci mutation is the main gyrA gene mutation, so clinicians should select antibiotics according to the sensitivity rest.