宿主因素对幽门螺杆菌感染患者菌株耐药性的影响

Influence of Host Factors on Drug Resistance of Helicobacter Pylori Infection

  • 摘要:
    目的 分析影响幽门螺杆菌(Helicobacter pylori, Hp)耐药性的宿主因素。
    方法 连续招募2021年11月—2023年10月于南京医科大学附属苏州医院就诊的Hp感染患者为研究对象。取内镜活检标本进行病理诊断、Hp菌株培养和药敏检测, 并通过电子病历及问卷收集、纳入19项涉及患者基本资料、生活方式、饮食习惯、健康状况的指标, 采用Logistic回归法评估宿主因素与Hp菌株对克拉霉素、左氧氟沙星、阿莫西林、呋喃唑酮、四环素、甲硝唑6种抗菌药物耐药性的相关性。
    结果 共入选符合纳入与排除标准的Hp感染患者115例(Hp菌株115株)。其中男性53例(46.09%)、女性62例(53.91%), 平均年龄(45.16±13.39)岁。胃镜病理: 浅表性胃炎86例(74.78%), 萎缩性胃炎6例(5.22%), 肠上皮化生14例(12.17%), 低级别上皮内瘤变6例(5.22%), 高级别上皮内瘤变/胃癌3例(2.61%)。Hp菌株对抗菌药物的耐药率由高至低分别为甲硝唑(91.30%, 105/115)、左氧氟沙星(53.04%, 61/115)、克拉霉素(51.30%, 59/115), 未发现对阿莫西林、呋喃唑酮、四环素耐药菌株。双重耐药: 左氧氟沙星+甲硝唑双重耐药率为50.43%(58/115), 克拉霉素+甲硝唑双重耐药率为47.83%(55/115), 克拉霉素+左氧氟沙星双重耐药率为36.52%(42/115)。多重耐药: 克拉霉素+左氧氟沙星+甲硝唑三重耐药率为34.78%(40/115)。多因素Logistic回归分析结果显示(由于无对甲硝唑敏感毒株, 多因素分析未纳入该药物), 既往Hp根除史(OR=74.782, 95% CI: 10.377~538.886, P<0.001)、家庭饮用水来源为自来水(OR=4.919, 95% CI: 1.160~20.859, P=0.031)可增加菌株对克拉霉素的耐药风险, 年龄≥50岁可增加菌株对左氧氟沙星的耐药风险(OR=4.261, 95% CI: 1.420~12.785, P=0.010), 既往Hp根除史(OR=5.855, 95% CI: 2.209~15.517, P<0.001)、年龄40~59岁(OR=3.269, 95% CI: 1.254~8.520, P=0.015)可增加菌株对克拉霉素+左氧氟沙星双重耐药的风险。
    结论 南京医科大学附属苏州医院Hp感染患者分离培养的菌株对甲硝唑、左氧氟沙星、克拉霉素的耐药率较高, 且双重耐药、多重耐药现象突出。年龄、既往Hp根除史、家庭饮用水来源可能与克拉霉素、左氧氟沙星单药或双重耐药具有相关性。临床在进行Hp根除时, 应综合考量, 合理选择抗菌药物, 个体化制订治疗方案。

     

    Abstract:
    Objective To analyze the host factors affecting the drug resistance of Helicobacter pylori (Hp).
    Methods Patients with Hp infection were consecutively recruited in the Affiliated Suzhou Hospital of Nanjing Medical University from November 2021 to October 2023. Endoscopic biopsy specimens were collected for pathological diagnosis, Hp strain culture and antimicrobial susceptibility test. Nineteen factors involving the basic information, lifestyle, dietary habits, and health status of the patients were collected through electronic medical records and questionnaires. Logistic regression was used to evaluate the association between the patients' factors and drug resistance to clarithromycin, levofloxacin, amoxicillin, furazolidone, tetracycline and metronidazole.
    Results A total of 115 patients (Hp strain 115) with Hp infection who met the inclusion and exclusion criteria were enrolled. There were 53 males (46.09%) and 62 females (53.91%), with an average age of (45.16±13.39) years. Gastroscopic pathology showed 86 cases (74.78%) of superficial gastritis, 6 cases (5.22%) of atrophic gastritis, 14 cases (12.17%) of intestinal metaplasia, 6 cases (5.22%) of low-grade intraepithelial neoplasia, and 3 cases (2.61%) of high-grade intraepithelial neoplasia/gastric cancer. The drug resistance rates of Hp strains to metronidazole, levofloxacin and clarithromycin were 91.30% (105/115), 53.04% (61/115) and 51.30% (59/115), respectively. Resistance to amoxicillin, furazolidone and tetracycline was not found. Dual drug resistance: levofloxacin + metronidazole dual resistance rate was 50.43% (58/115), clarithromycin + metronidazole dual resistance rate was 47.83% (55/115), clarithromycin + levofloxacin dual resistance rate was 36.52% (42/115). Multidrug resistance: clarithromycin + levofloxacin + metronidazole triple resistance rate was 34.78% (40/115). Multivariate Logistic regression analysis showed that (metronidazole was not included in the multivariate analysis due to the absence of sensitive strains), previous Hp eradication history (OR=74.782, 95% CI: 10.377-538.886, P < 0.001) and tap water (OR=4.919, 95% CI: 1.160-20.859, P=0.031) increased the risk of clarithromycin resistance, and age ≥50 years increased the risk of levofloxacin resistance (OR=4.261, 95% CI: 1.420-12.785, P=0.010), previous Hp eradication history (OR=5.855, 95% CI: 2.209-15.517, P < 0.001), 40-59 years old (OR= 3.269, 95% CI: 1.254-8.520, P=0.015) increased the risk of dual resistance to clarithromycin and levofloxacin.
    Conclusions The drug resistance rate of Hp strains isolated from patients in the Affiliated Suzhou Hospital of Nanjing Medical University to metronidazole, levofloxacin and clarithromycin were high, and dual drug resistance and multidrug resistance were prominent. Age, previous Hp eradication history and drinking water source may be associated with single or dual drug resistance to clarithromycin and levofloxacin. Comprehensive consideration, reasonable selection of antibiotics and individualized treatment should be taken into account during Hp eradication.

     

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