Success of Helicobacter pylori Guideline-based Treatment of Newly Diagnosed and Previously Treated Patients During 2007–2021 in Edmonton, Alberta

Thomas Krahn, Jonas Buttenschoen, Pernilla D’Souza, S. Girgis, A. Thiesen, Robert Rennie, LeeAnn Turnbull, Sander Veldhuyzen van Zanten
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Abstract

Updated 2016 Helicobacter pylori consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days. This was a retrospective cohort study to describe and compare the efficacy of anti-Helicobacter treatment regimens over the periods 2007–2015 and 2016–2021 as well as antibiotic resistance. A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed H. pylori treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients. H. pylori-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016–2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) (P < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7–26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016–2021 and sequential therapy in 2007–2015 (83% [66/80]) (P = 0.535, RD 4%, 95% CI −8.5–16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016–2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007–2015 to 2016–2021 (28% [13/46] to 61% [35/57], P < 0.05, RD 33%, 95% CI 11.6–54.4%). Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures H. pylori in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50–57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in H. pylori is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.
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2007-2021 年间艾伯塔省埃德蒙顿市幽门螺杆菌新诊断患者和既往治疗患者的指导性治疗成功率
2016 年更新的幽门螺杆菌共识指南建议将质子泵抑制剂(PPI)-阿莫西林-甲硝唑-克拉霉素(PAMC)或铋剂四联疗法(PPI-铋剂-甲硝唑-四环素、PBMT)作为一线疗法,PBMT或PPI-阿莫西林-左氧氟沙星(PAL)作为二线或三线疗法,PPI-阿莫西林-利福布汀(PAR)作为四线疗法,疗程为10天。 这是一项回顾性队列研究,旨在描述和比较2007-2015年和2016-2021年期间抗肝杆菌治疗方案的疗效以及抗生素耐药性。 改良意向治疗(mITT)分析用于分析疗法的成功率。mITT包括所有接受幽门螺杆菌治疗并至少进行过一次后续治愈试验的患者。其中包括无法完成治疗或不坚持治疗的患者。通过单变量和多变量逻辑回归分析了治疗失败的风险因素。对一小部分患者进行了耐药性检测。 在艾伯塔省埃德蒙顿接受治疗的幽门螺杆菌阳性患者被纳入 mITT 分析:2007 年至 2015 年为 334/387(86%)人,2016 年至 2021 年为 193/199(97%)人。2016-2021 年间,78%(150/193)的患者接受了基于指南的累积治疗,80%(120/150)的患者成功治愈。新确诊患者的治愈率为88%(52/59),而既往治疗失败患者的治愈率为75%(68/91)(P < 0.05,风险差异[RD] 14%,95%置信区间[CI] 1.7-26.3%)。最有效的一线治疗方案是2016-2021年持续14天的PAMC(87% [45/52])和2007-2015年的序贯疗法(83% [66/80])(P = 0.535,RD 4%,95% CI -8.5-16.5%)。当其他治疗失败时,2007-2015年期间使用PAR治疗的成功率为50%(2/4),2016-2021年期间为57%(21/37)。近期(2016-2021年)对克拉霉素和甲硝唑的耐药率较高,分别为78%(50/64)和56%(29/52)。2007 年至 2015 年,克拉霉素和甲硝唑的耐药率分别为 80%(36/45)和 83%(38/46)。从2007-2015年到2016-2021年,左氧氟沙星耐药率显著增加(28% [13/46] 到 61% [35/57],P < 0.05,RD 33%,95% CI 11.6-54.4%)。 在 88% 的新诊断患者中,采用 PAMC 一线治疗,然后是 PBMT、PAL 和 PAR 的算法治疗可治愈幽门螺杆菌。PAR疗法的治愈率并不理想(成功率为50%-57%),但鉴于左氧氟沙星耐药率不断上升,可将其视为三线疗法而非四线疗法。幽门螺杆菌对克拉霉素、甲硝唑和左氧氟沙星的抗生素耐药性很常见,经常导致治疗失败。
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