Introduction. Helicobacter pylori is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant H. pylori as a high priority pathogen for drug development, due to increasing antibiotic resistance globally. Hypothesis/Gap Statement. There is no routine surveillance of H. pylori primary antimicrobial sensitivities in the UK, and published data are lacking. Aim. This study aimed to characterize antimicrobial sensitivities of isolates collected in Nottingham, UK, between 2001 and 2018. Methodology. Gastric biopsy samples were collected, with informed written consent and ethics approval, from 162 patients attending the Queen’s Medical Centre in Nottingham for an upper GI tract endoscopy. Antibiotic sensitivity was assessed using E-Tests and a more cost-effective disc diffusion test. Results. The clarithromycin, amoxicillin and levofloxacin disc diffusion tests provided identical results to E-Tests on a subset of 30 isolates. Disparities were observed in the metronidazole test results, however. In total, 241 isolates from 162 patients were tested using at least one method. Of all isolates, 28 % were resistant to clarithromycin, 62 % to metronidazole and 3 % to amoxicillin, which are used in first-line therapies. For those antibiotics used in second- and third-line therapies, 4 % were resistant to levofloxacin and none of the isolates were resistant to tetracycline. Resistance to more than one antibiotic was found in 27 % of isolates. The frequency of patients with a clarithromycin-resistant strain increased dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (P=0.011). For the same time periods, there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; P=0.05). The frequencies of clarithromycin and metronidazole resistance were higher in isolates from patients who had previously received eradication therapy, compared to those who had not (40 % versus 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of isolates from the antrum and corpus regions of the same patient’s stomach, only six had differences in their antimicrobial susceptibility profiles. Conclusion. Although there was high and increasing resistance to clarithromycin and metronidazole, there was no resistance to tetracycline and the frequencies of amoxicillin and levofloxacin resistance were very low.

中文翻译：

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2001 年至 2018 年间在英国诺丁汉收集的幽门螺杆菌分离株中抗生素耐药性发生率较高

介绍。 幽门螺杆菌是消化性溃疡和胃癌的主要原因。最常见的治疗方案使用两种或三种抗生素和质子泵抑制剂（PPI）的组合来抑制胃酸。由于全球抗生素耐药性不断增加，世界卫生组织将克拉霉素耐药性幽门螺杆菌指定为药物开发的高度优先病原体。假设/差距陈述。英国没有对幽门螺杆菌主要抗菌药物敏感性进行常规监测，也缺乏已发表的数据。目的。本研究旨在表征 2001 年至 2018 年间在英国诺丁汉收集的分离株的抗菌敏感性。方法论。胃活检样本是从诺丁汉女王医疗中心进行上消化道内窥镜检查的 162 名患者身上采集的，并获得书面知情同意和伦理批准。使用电子测试和更具成本效益的纸片扩散测试评估抗生素敏感性。结果。克拉霉素、阿莫西林和左氧氟沙星纸片扩散试验对 30 个分离株的子集提供了与 E 试验相同的结果。然而，甲硝唑测试结果存在差异。总共使用至少一种方法对来自 162 名患者的 241 株分离株进行了测试。在所有分离株中，28% 对克拉霉素耐药，62% 对甲硝唑耐药，3% 对一线治疗中使用的阿莫西林耐药。对于二线和三线治疗中使用的抗生素，4% 对左氧氟沙星具有耐药性，并且没有分离株对四环素具有耐药性。27% 的分离株对一种以上抗生素具有耐药性。随着时间的推移，克拉霉素耐药株患者的发生率急剧增加：从 2001 年至 2005 年的 16% 增加到 2011 年至 2018 年的 40%（P = 0.011）。同一时期内，甲硝唑耐药菌株的数量也有所增加（从 58% 增加到 78%；P =0.05）。与未接受根除治疗的患者相比，克拉霉素和甲硝唑耐药率在先前接受过根除治疗的患者中更高（分别为 40% 与 77%、80% 与 92%）。在同一患者胃窦和胃体区域的 79 对分离株中，只有 6 对的抗菌敏感性存在差异。结论。尽管对克拉霉素和甲硝唑的耐药性较高且不断增加，但对四环素没有耐药性，对阿莫西林和左氧氟沙星的耐药率非常低。