Cui Rongli, Song Zhiqiang, Suo Baojun, Tian Xueli, Xue Yan, Meng Lingmei, Niu Zhanyue, Jin Zhu, Zhang Hejun, Zhou Liya
Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
Infect Drug Resist. 2021 May 11;14:1747-1756. doi: 10.2147/IDR.S305996. eCollection 2021.
It has not been fully confirmed whether the detection of resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test.
The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined.
The 551/602 subjects, who met the inclusion criteria, were subjected to culture for and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001).
A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of resistance genes has a good clinical application prospect.
耐药基因突变检测能否替代抗生素药物敏感性试验以指导临床个体化治疗尚未得到充分证实。因此,我们对此进行了研究,并探讨了抗生素敏感性基因检测的应用价值。
连续收集经内镜检查且快速尿素酶试验呈阳性患者的胃黏膜活检标本,进行组织病理学分析、培养、抗生素药物敏感性试验(E-test药敏试验)及抗生素敏感性基因检测(高通量核苷酸测序)。参与者接受三联加铋剂根除治疗(埃索美拉唑20mg、阿莫西林1000mg、克拉霉素500mg和枸橼酸铋钾220mg,每日2次,共14天)进行随访,并确定根除效果。
551/602名符合纳入标准的受试者进行了培养及抗生素药物敏感性测定;其中506例培养成功。结果显示,克拉霉素耐药率为38.9%,左氧氟沙星耐药率为31.0%。在489株菌株中,检测到克拉霉素和左氧氟沙星耐药基因的突变,提示基因型耐药。克拉霉素和左氧氟沙星耐药基因在敏感性(克拉霉素和左氧氟沙星分别为81.2%和69.7%)和特异性(克拉霉素和左氧氟沙星分别为88.9%和93.7%)方面与表型耐药一致。克拉霉素耐药组的根除率显著低于敏感组(意向性分析:52.1%对85.0%,P<0.001)。
克拉霉素和左氧氟沙星耐药基因与其表型耐药及临床疗效之间建立了相关性。耐药基因检测具有良好的临床应用前景。