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Clinical Resistance of Helicobacter pylori and Its Trend: A 10-year Data Analysis at Peking University People's Hospital
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摘要:
目的 基于北京大学人民医院近10年数据，分析临床分离的幽门螺杆菌(Helicobacter pylori, Hp)对常用抗菌药物的耐药情况，以期为临床合理用药提供依据。 方法 回顾性收集2011年5月—2021年12月北京大学人民医院消化科门诊患者胃黏膜活检标本分离的Hp菌株的药敏试验数据，统计Hp对阿莫西林、甲硝唑、克拉霉素、左氧氟沙星及四环素5种抗菌药物的耐药率及双重/多重耐药情况。 结果 共纳入分离自402份胃黏膜标本(120例患者)且培养阳性的Hp 120株，培养阳性率为29.85%。Hp对甲硝唑(75.0%)和克拉霉素(72.5%)的耐药率较高，对左氧氟沙星的耐药率居中(45.8%)，对阿莫西林(12.5%)和四环素(4.2%)的耐药率相对较低。Hp对克拉霉素、阿莫西林的耐药率受患者年龄的影响不明显，对甲硝唑、左氧氟沙星的耐药率随患者年龄增加整体呈逐渐升高的趋势，对四环素的耐药率随患者年龄增加呈逐渐降低趋势；女性患者对左氧氟沙星的耐药率高于男性(56.7%比32.1%，P=0.007)；随时间推移，Hp对克拉霉素的耐药率整体呈逐渐升高趋势，对左氧氟沙星的耐药率呈先增加后降低的趋势，对甲硝唑的耐药率呈波动之势且整体偏高，对阿莫西林、四环素的耐药率受时间变化的影响相对不明显且整体偏低。未发现对5种抗菌药物同时耐药的Hp菌株。双重耐药率为25.0%，其中以甲硝唑与克拉霉素同时耐药最为常见(20.0%)；多重耐药率为44.2%，其中以甲硝唑+克拉霉素+左氧氟沙星同时耐药最为常见(32.5%)。 结论 北京大学人民医院分离的Hp菌株对甲硝唑、克拉霉素及左氧氟沙星的耐药率较高，且多重耐药现象严重。临床在开展经验性Hp根治疗法时，应合理选择用药方案，必要时应进行药敏试验，以指导治疗方案的制定。 Abstract:Objective To study the resistance of Helicobacter pylori(Hp) isolated from Peking University People's Hospital to commonly used antibiotics, in order to provide basis for clinical rational drug use. Methods The drug susceptibility test data of Hp strains isolated from gastric mucosal biopsy specimens of outpatients in the Department of Gastroenterology, Peking University People's Hospital from May 2011 to December 2021 were retrospectively collected. The drug resistance rate and dual/multiple drug resistance of Hp to amoxicillin, metronidazole, clarithromycin, levofloxacin and tetracycline were statistically analyzed. Results A total of 120 Hp strains isolated from 402 gastric mucosa specimens (120 patients) and cultured positive were included, with a culture positive rate of 29.85%. The resistance rates of Hp to metronidazole (75.0%) and clarithromycin (72.5%) were relatively high, while the resistance rates to levofloxacin (45.8%), amoxicillin (12.5%) and tetracycline (4.2%) were relatively low. The drug resistance of Hp to clarithromycin and amoxicillin was not significantly affected by the age of the patients. The drug resistance rate to metronidazole and levofloxacin increased with the age of the patients, and the drug resistance rate to tetracycline decreased with the age of the patients. The resistance rate of female patients to levofloxacin was higher than that of male patients (56.7% vs. 32.1%, P=0.007). Over time, the resistance rate of Hp to clarithromycin increased gradually, the resistance rate to levofloxacin increased first and then decreased, the resistance rate to metronidazole fluctuated and was high overall, and the resistance rate to amoxicillin and tetracycline was not significantly affected by time and was relatively low overall. No Hp strains resistant to all five kinds of antibiotics were found. Dual drug resistance rate was 25.0%, with the simultaneous resistance of metronidazole and clarithromycin being the most common (20.0%); multiple drug resistance rate was 44.2%, with the simultaneous resistance of metronidazole + clarithromycin + levofloxacin being the most common (32.5%). Conclusions The resistance rate of Hp strains isolated from Peking University People's Hospital to metronidazole, clarithromycin and levofloxacin is high, and multiple drug resistance is serious. When carrying out empirical Hp root therapy in clinic, the drug regimen should be reasonably selected, and drug sensitivity test should be conducted when necessary, so as to guide the formulation of treatment regimen. -
Key words:
- Helicobacter pylori /
- antibiotic resistance /
- multidrug resistance /
- triple therapy
作者贡献：张菲菲负责资料收集、论文撰写；王启负责论文修订；李曙光、王占伟、梁馨月、孟涵、杨硕负责实验室检查；王辉负责论文修订和审阅定稿。利益冲突：所有作者均声明不存在利益冲突 -
表 1 Hp对5种抗菌药物的体外药敏试验结果(n=120)
抗菌药物 耐药率(%) 中介率(%) 敏感率(%) MIC50(mg/L) MIC90(mg/L) MIC范围(mg/L) 甲硝唑 75.0 0 25.0 256 ＞256 0.016~512 克拉霉素 72.5 0.8 26.7 8 ＞256 0.010~512 左氧氟沙星 45.8 0 54.2 0.5 64 0.002~512 阿莫西林 12.5 0 87.5 0.016 0.25 0.010~512 四环素 4.2 0 95.8 0.023 0.25 0.008~16 Hp：幽门螺杆菌；MIC50/MIC90：抑制50%或90% Hp生长所需的最低抑菌浓度；MIC: 最低抑菌浓度 
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表 2 不同性别Hp感染患者对5种抗菌药物的耐药情况比较[n(%)]
抗菌药物 男性(n=53) 女性(n=67) P值 甲硝唑 42(79.2) 48(71.6) 0.384 克拉霉素 38(71.7) 49(73.1) 0.861 左氧氟沙星 17(32.1) 38(56.7) 0.007 阿莫西林 9(17.0) 6(9.0) 0.233 四环素 3(5.7) 2(3.0) 0.466 Hp：同表 1
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表 3 Hp对5种抗菌药物双重/多重耐药结果展示(n=120)
抗菌药物 耐药菌株数(n) 耐药率(%) 双重耐药 30 25.0 甲硝唑+克拉霉素 24 20.0 左氧氟沙星+克拉霉素 3 2.5 甲硝唑+左氧氟沙星 1 0.8 克拉霉素+阿莫西林 1 0.8 甲硝唑+阿莫西林 1 0.8 多重耐药 53 44.2 甲硝唑+克拉霉素+左氧氟沙星 39 32.5 甲硝唑+克拉霉素+阿莫西林+左氧氟沙星 6 5.0 甲硝唑+阿莫西林+克拉霉素 2 1.7 甲硝唑+克拉霉素+四环素 1 0.8 左氧氟沙星+阿莫西林+克拉霉素 1 0.8 克拉霉素+阿莫西林+四环素 1 0.8 甲硝唑+阿莫西林+克拉霉素+四环素 2 1.7 甲硝唑+阿莫西林+克拉霉素+四环素+左氧氟沙星 1 0.8 Hp：同表 1
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