The efficacy of keverprazan–amoxicillin dual therapy (KA) in the treatment of Helicobacter pylori (H. pylori) has not yet been demonstrated. Here, we aimed to compare the eradication rate of the KA regimen with esomeprazole-based bismuth quadruple therapy (EBQT) containing amoxicillin and clarithromycin for H. pylori initial eradication in the Chinese population.
Methods
Patients aged between 18–75 years were randomly assigned into KA group or the EBQT group. The KA group patients received keverprazan 20 mg (b.i.d.) and amoxicillin 1.0 g (t.i.d.) for 14 days. The EBQT group patients took esomeprazole 20 mg (b.i.d.), amoxicillin 1.0 g (b.i.d.), clarithromycin 0.5 g (b.i.d.), and bismuth potassium citrate 220 mg (b.i.d.) for 14 days. The primary outcome was the H. pylori eradication rate 28 days after therapy. Secondary outcomes included compliance and adverse events.
Results
A total of 394 patients were enrolled in this study. Eradication rates in the KA group and the EBQT group were 87.88% and 84.18% in intention-to-treat analysis (ITT) (rate difference: 3.70%, 95% CI: −3.14% to 10.53%), 92.55% and 88.24% in modified ITT analysis (rate difference: 4.32%, 95% CI: −1.63% to 10.27%), and 93.99% and 90.56% in per-protocol analysis (PP) (rate difference: 3.43%, 95% CI: −2.05% to 8.92%), respectively. The eradication rates for the KA group were not inferior to those of the EBQT group in ITT, modified ITT, and PP analysis. The incidences of nausea and overall adverse effects in the KA group were significantly lower than those of the EBQT group.
Conclusions
Keverprazan 20 mg twice daily with high-dose amoxicillin demonstrates a noninferior efficacy to bismuth quadruple therapy for initial H. pylori eradication.
Trial Registration
Chinese Clinical Trial Registry, registration No: ChiCTR2400092511
{"title":"Efficacy and Safety of Keverprazan–Amoxicillin Dual Regimen in Initial Eradication of Helicobacter pylori Infection: A Multicenter, Randomized Controlled Trial","authors":"Shanshan Wei, Zhihao Huang, Huizhen Xiong, Ji Wu, Dihua Mei, Jing Zhao, Wei Liu, Qingyun Liu, Yu Lin, Fang Liu, Xiang Peng, Honglei Chen","doi":"10.1111/hel.70100","DOIUrl":"10.1111/hel.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The efficacy of keverprazan–amoxicillin dual therapy (KA) in the treatment of <i>Helicobacter pylori</i> (<i>H. pylori</i>) has not yet been demonstrated. Here, we aimed to compare the eradication rate of the KA regimen with esomeprazole-based bismuth quadruple therapy (EBQT) containing amoxicillin and clarithromycin for <i>H. pylori</i> initial eradication in the Chinese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients aged between 18–75 years were randomly assigned into KA group or the EBQT group. The KA group patients received keverprazan 20 mg (b.i.d.) and amoxicillin 1.0 g (t.i.d.) for 14 days. The EBQT group patients took esomeprazole 20 mg (b.i.d.), amoxicillin 1.0 g (b.i.d.), clarithromycin 0.5 g (b.i.d.), and bismuth potassium citrate 220 mg (b.i.d.) for 14 days. The primary outcome was the <i>H. pylori</i> eradication rate 28 days after therapy. Secondary outcomes included compliance and adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 394 patients were enrolled in this study. Eradication rates in the KA group and the EBQT group were 87.88% and 84.18% in intention-to-treat analysis (ITT) (rate difference: 3.70%, 95% CI: −3.14% to 10.53%), 92.55% and 88.24% in modified ITT analysis (rate difference: 4.32%, 95% CI: −1.63% to 10.27%), and 93.99% and 90.56% in per-protocol analysis (PP) (rate difference: 3.43%, 95% CI: −2.05% to 8.92%), respectively. The eradication rates for the KA group were not inferior to those of the EBQT group in ITT, modified ITT, and PP analysis. The incidences of nausea and overall adverse effects in the KA group were significantly lower than those of the EBQT group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Keverprazan 20 mg twice daily with high-dose amoxicillin demonstrates a noninferior efficacy to bismuth quadruple therapy for initial <i>H. pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Chinese Clinical Trial Registry, registration No: ChiCTR2400092511</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Population-based screen-and-treat of Helicobacter pylori infection, a well-established cause of gastric cancer, is emerging as an effective strategy to reduce gastric cancer incidence and mortality, in line with recommendations from the working group convened by the International Agency for Research on Cancer. This report reviews the development of the population-based H. pylori screen-and-treat strategy as a healthcare policy for gastric cancer prevention in Taiwan from 2004 to 2025, tracing its evolution from localized pilot programs to regional initiatives and, ultimately, to full population-wide implementation. To support systematic implementation at the population level, Taiwan adopted a three-tiered foundation that includes: (1) a centralized planning committee; (2) screening service delivery through primary care providers, guided by clinical guidelines established by medical societies; and (3) community engagement to raise awareness of stomach health and promote participation in screen-and-treat programs through social media campaigns. Program execution strictly follows the principles of organized screening, supported by standardized quality indicators, integrated digital tracking systems, structured audit mechanisms, and both effectiveness and cost-effectiveness assessments. Strategies are tailored to local contexts: in the Matsu Islands, mass screening using the 13C urea breath test and subsequent eradication treatment led to reductions in H. pylori prevalence and gastric cancer incidence and mortality; in Changhua County, a pragmatic randomized clinical trial showed that stool sample-based screening using H. pylori stool antigen and fecal immunochemical testing improved participation and reduced gastric cancer incidence; and in indigenous communities, household-based approaches utilizing the 13C urea breath test could enhance H. pylori detection rate and reduce the intrafamilial transmission. In addition to the continuous assessment of its effectiveness in preventing both gastric cancer and peptic ulcer disease, it is also essential to evaluate the potential impacts on antibiotic resistance and gut microbial succession after mass H. pylori eradication. All these programs consistently maintain high standards of quality and equity, ensuring accessibility for diverse populations with varying socioeconomic positions. Collectively, it demonstrates how robust scientific evaluations, when combined with organized screening principles and systematic performance monitoring, can be effectively translated into sustainable, evidence-based programs for population-wide gastric cancer prevention.
{"title":"Gastric Cancer Prevention in Taiwan: Past Achievements and Future Perspectives","authors":"Shu-Lin Chuang, Teresa Cheng-Chieh Chu, Tsung-Hsien Chiang, Yi-Ru Chen, Wei-Yi Lei, Chien-Lin Chen, Ming-Jong Bair, Jeng-Yih Wu, Deng-Chyang Wu, Felice Tien O'Donnell, Hui-Wen Tien, Sherry Yueh-Hsia Chiu, Hsiu-Chi Cheng, Yu-Hsin Hsu, Tsui-Hsia Hsu, Pei-Chun Hsieh, Li-Ju Lin, Yi-Maun Subeq, Shu-Hui Wen, Chia-Hsiang Chu, Ming-Shiang Wu, Yi-Chia Lee","doi":"10.1111/hel.70102","DOIUrl":"https://doi.org/10.1111/hel.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Population-based screen-and-treat of <i>Helicobacter pylori</i> infection, a well-established cause of gastric cancer, is emerging as an effective strategy to reduce gastric cancer incidence and mortality, in line with recommendations from the working group convened by the International Agency for Research on Cancer. This report reviews the development of the population-based <i>H. pylori</i> screen-and-treat strategy as a healthcare policy for gastric cancer prevention in Taiwan from 2004 to 2025, tracing its evolution from localized pilot programs to regional initiatives and, ultimately, to full population-wide implementation. To support systematic implementation at the population level, Taiwan adopted a three-tiered foundation that includes: (1) a centralized planning committee; (2) screening service delivery through primary care providers, guided by clinical guidelines established by medical societies; and (3) community engagement to raise awareness of stomach health and promote participation in screen-and-treat programs through social media campaigns. Program execution strictly follows the principles of organized screening, supported by standardized quality indicators, integrated digital tracking systems, structured audit mechanisms, and both effectiveness and cost-effectiveness assessments. Strategies are tailored to local contexts: in the Matsu Islands, mass screening using the <sup>13</sup>C urea breath test and subsequent eradication treatment led to reductions in <i>H. pylori</i> prevalence and gastric cancer incidence and mortality; in Changhua County, a pragmatic randomized clinical trial showed that stool sample-based screening using <i>H. pylori</i> stool antigen and fecal immunochemical testing improved participation and reduced gastric cancer incidence; and in indigenous communities, household-based approaches utilizing the <sup>13</sup>C urea breath test could enhance <i>H. pylori</i> detection rate and reduce the intrafamilial transmission. In addition to the continuous assessment of its effectiveness in preventing both gastric cancer and peptic ulcer disease, it is also essential to evaluate the potential impacts on antibiotic resistance and gut microbial succession after mass <i>H. pylori</i> eradication. All these programs consistently maintain high standards of quality and equity, ensuring accessibility for diverse populations with varying socioeconomic positions. Collectively, it demonstrates how robust scientific evaluations, when combined with organized screening principles and systematic performance monitoring, can be effectively translated into sustainable, evidence-based programs for population-wide gastric cancer prevention.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae Yong Park, Su Jin Hong, Il Ju Choi, Gwang Ho Baik, Sun Moon Kim, Jong-Jae Park, Seong Woo Jeon, Kyung-Oh Kim, Sang Kil Lee, Hwoon-Yong Jung, Jung-Hwan Oh, Chan Hyuk Park, Sang Wook Kim, Ki-Nam Shim, Sam Ryong Jee, Hee Seok Moon, Jeong Seop Moon, Cheol Woong Choi, Wan-Sik Lee, Jae Gyu Kim
Background
Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.
Aim
This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication.
Methods
This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023–April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of −10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments.
Results
Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events.
Conclusion
Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication.
{"title":"Tegoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Phase III Multicenter Randomized Clinical Trial","authors":"Jae Yong Park, Su Jin Hong, Il Ju Choi, Gwang Ho Baik, Sun Moon Kim, Jong-Jae Park, Seong Woo Jeon, Kyung-Oh Kim, Sang Kil Lee, Hwoon-Yong Jung, Jung-Hwan Oh, Chan Hyuk Park, Sang Wook Kim, Ki-Nam Shim, Sam Ryong Jee, Hee Seok Moon, Jeong Seop Moon, Cheol Woong Choi, Wan-Sik Lee, Jae Gyu Kim","doi":"10.1111/hel.70106","DOIUrl":"10.1111/hel.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line <i>Helicobacter pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023–April 2024). Treatment-naïve adults with <i>H. pylori</i> infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was <i>H. pylori</i> eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of −10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for <i>H. pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT05933031</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12800724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Standard triple therapy fails to eradicate Helicobacter pylori (H. pylori) in at least 20% of the cases, largely due to antibiotic resistance. Non-bismuth concomitant quadruple therapy has emerged as a widely used alternative therapy.
Aim
To conduct a meta-analysis evaluating the efficacy and safety of concomitant therapy—comprising a proton pump inhibitor, clarithromycin, amoxicillin, and a nitroimidazole—for H. pylori eradication.
Methods
A systematic search of PubMed, EMBASE, and relevant conference abstracts was conducted through November 2025. Meta-analyses included studies assessing concomitant therapy and comparisons with standard triple, sequential, hybrid, and bismuth-based quadruple therapies.
Results
A total of 144 studies (92 randomized clinical trials), involving 26,467 patients were included. Pooled eradication rates for concomitant therapy were 86% (intention-to-treat) and 91% (per-protocol). Analysis of randomized clinical trials showed that concomitant therapy demonstrated significantly higher efficacy than triple therapy (risk difference [RD] = 0.11; 95% CI = 0.08–0.13) and sequential therapy (RD = 0.03; 0.01–0.05), but similar efficacy to hybrid and bismuth quadruple regimens (containing nitroimidazole–tetracycline and clarithromycin–amoxicillin). Concomitant therapy achieved 87% and 95% eradication rates in clarithromycin- and metronidazole-resistant strains, respectively, but only 67% in dual-resistant strains. Adverse events were frequent (38%), although generally mild.
Conclusions
Concomitant therapy is a highly effective first-line option for H. pylori eradication, particularly in single clarithromycin- or nitroimidazole-resistant strains. However, its efficacy is reduced in dual-resistant cases, in which alternative regimens may be preferred. Overall, its efficacy is comparable to that of hybrid and bismuth quadruple therapy. Its tolerability is generally acceptable.
{"title":"Non-Bismuth Quadruple Concomitant Treatment for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis","authors":"Pablo Parra, Olga P. Nyssen, Javier P. Gisbert","doi":"10.1111/hel.70099","DOIUrl":"https://doi.org/10.1111/hel.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Standard triple therapy fails to eradicate <i>Helicobacter pylori</i> (<i>H. pylori</i>) in at least 20% of the cases, largely due to antibiotic resistance. Non-bismuth concomitant quadruple therapy has emerged as a widely used alternative therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To conduct a meta-analysis evaluating the efficacy and safety of concomitant therapy—comprising a proton pump inhibitor, clarithromycin, amoxicillin, and a nitroimidazole—for <i>H. pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of PubMed, EMBASE, and relevant conference abstracts was conducted through November 2025. Meta-analyses included studies assessing concomitant therapy and comparisons with standard triple, sequential, hybrid, and bismuth-based quadruple therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 144 studies (92 randomized clinical trials), involving 26,467 patients were included. Pooled eradication rates for concomitant therapy were 86% (intention-to-treat) and 91% (per-protocol). Analysis of randomized clinical trials showed that concomitant therapy demonstrated significantly higher efficacy than triple therapy (<i>risk difference</i> [RD] = 0.11; 95% CI = 0.08–0.13) and sequential therapy (RD = 0.03; 0.01–0.05), but similar efficacy to hybrid and bismuth quadruple regimens (containing nitroimidazole–tetracycline and clarithromycin–amoxicillin). Concomitant therapy achieved 87% and 95% eradication rates in clarithromycin- and metronidazole-resistant strains, respectively, but only 67% in dual-resistant strains. Adverse events were frequent (38%), although generally mild.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Concomitant therapy is a highly effective first-line option for <i>H. pylori</i> eradication, particularly in single clarithromycin- or nitroimidazole-resistant strains. However, its efficacy is reduced in dual-resistant cases, in which alternative regimens may be preferred. Overall, its efficacy is comparable to that of hybrid and bismuth quadruple therapy. Its tolerability is generally acceptable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gasser El-Azab, Sherief Abdel Salam, Ehab Moustafa, Ahmed Abuoelhassan, Ayman Shamseya, Ahmed Ellakany, Usama Abdelaal, Medhat Assem, Fatma Khalil, Amal Mahmoud, Maha Elsabaawy, Boshra Hussein, Mohammed Ezz-Eldin, Sahar Hassany, Nariman Zaghloul, Mai Magdy
Background
Eradication of Helicobacter pylori remains challenging in countries with high antimicrobial resistance and limited access to bismuth-based therapies. Quinolone-containing regimens represent a practical alternative, yet comparative data between levofloxacin- and moxifloxacin-based nitazoxanide quadruple therapies are scarce, particularly in Egypt. This multicenter trial evaluated the efficacy, safety, and tolerability of two nitazoxanide-based second-line regimens after failure of first-line eradication therapy.
Methods
In this prospective, randomized, single-blind, parallel-group study conducted at six Egyptian centers, adults aged 18–70 years with documented failure of first-line H. pylori therapy were enrolled. Patients were randomized 1:1 to receive either LNDL (levofloxacin 750 mg once daily, nitazoxanide 500 mg twice daily, doxycycline 100 mg twice daily, lansoprazole 30 mg twice daily) or MNDL (moxifloxacin 400 mg once daily with the same adjunct medications) for 14 days. Eradication was assessed using a stool antigen test ≥ 4 weeks after treatment. Safety, tolerability, and symptom improvement were recorded. Analyses were performed using both intention-to-treat (ITT) and per-protocol (PP) populations.
Results
A total of 430 patients were randomized. ITT eradication rates were 65.6% (95% CI: 59.2% – 72%) for LNDL and 74.9% (95% CI: 69% – 80.7%) for MNDL (p = 0.035). PP eradication rates were 70.9% (95% CI: 64.5% – 77.2%) and 78.5% (95% CI: 72.9% – 84.2%), respectively (p = 0.076). Among patients previously treated with levofloxacin, MNDL achieved significantly higher eradication rates than LNDL (65.8%, 95% CI: 50–81.6 vs. 42.6%, 95% CI: 29–56.2, p = 0.028). Both regimens produced significant symptom improvement and were well tolerated; no serious adverse events occurred.
Conclusion
Both nitazoxanide-based quinolone quadruple regimens demonstrated modest but clinically relevant efficacy as second-line therapy. Moxifloxacin showed superior performance in patients with prior levofloxacin exposure. These findings support the use of moxifloxacin-based rescue therapy in settings with high resistance and limited access to bismuth-containing regimens.
{"title":"Efficacy and Safety of Levofloxacin- Versus Moxifloxacin-Based Nitazoxanide Quadruple Therapy as Second-Line Treatment for Helicobacter pylori in Egypt: A Randomized Multicenter Trial","authors":"Gasser El-Azab, Sherief Abdel Salam, Ehab Moustafa, Ahmed Abuoelhassan, Ayman Shamseya, Ahmed Ellakany, Usama Abdelaal, Medhat Assem, Fatma Khalil, Amal Mahmoud, Maha Elsabaawy, Boshra Hussein, Mohammed Ezz-Eldin, Sahar Hassany, Nariman Zaghloul, Mai Magdy","doi":"10.1111/hel.70104","DOIUrl":"10.1111/hel.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eradication of <i>Helicobacter pylori</i> remains challenging in countries with high antimicrobial resistance and limited access to bismuth-based therapies. Quinolone-containing regimens represent a practical alternative, yet comparative data between levofloxacin- and moxifloxacin-based nitazoxanide quadruple therapies are scarce, particularly in Egypt. This multicenter trial evaluated the efficacy, safety, and tolerability of two nitazoxanide-based second-line regimens after failure of first-line eradication therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective, randomized, single-blind, parallel-group study conducted at six Egyptian centers, adults aged 18–70 years with documented failure of first-line <i>H. pylori</i> therapy were enrolled. Patients were randomized 1:1 to receive either LNDL (levofloxacin 750 mg once daily, nitazoxanide 500 mg twice daily, doxycycline 100 mg twice daily, lansoprazole 30 mg twice daily) or MNDL (moxifloxacin 400 mg once daily with the same adjunct medications) for 14 days. Eradication was assessed using a stool antigen test ≥ 4 weeks after treatment. Safety, tolerability, and symptom improvement were recorded. Analyses were performed using both intention-to-treat (ITT) and per-protocol (PP) populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 430 patients were randomized. ITT eradication rates were 65.6% (95% CI: 59.2% – 72%) for LNDL and 74.9% (95% CI: 69% – 80.7%) for MNDL (<i>p</i> = 0.035). PP eradication rates were 70.9% (95% CI: 64.5% – 77.2%) and 78.5% (95% CI: 72.9% – 84.2%), respectively (<i>p</i> = 0.076). Among patients previously treated with levofloxacin, MNDL achieved significantly higher eradication rates than LNDL (65.8%, 95% CI: 50–81.6 vs. 42.6%, 95% CI: 29–56.2, <i>p</i> = 0.028). Both regimens produced significant symptom improvement and were well tolerated; no serious adverse events occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both nitazoxanide-based quinolone quadruple regimens demonstrated modest but clinically relevant efficacy as second-line therapy. Moxifloxacin showed superior performance in patients with prior levofloxacin exposure. These findings support the use of moxifloxacin-based rescue therapy in settings with high resistance and limited access to bismuth-containing regimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The global rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections, including those caused by Helicobacter pylori. This study investigates potential inhibitors of the H. pylori urease enzyme, a key virulence factor that enables survival in the highly acidic gastric environment. A virtual screening of 1773 FDA-approved drugs was performed, followed by molecular dynamics simulations. Among the top candidates, Natamycin, Zavegepant, Midostaurin, Avacopan, and Metolazone displayed significant binding affinities towards urease. Further simulations confirmed the stability and favorable interaction profiles of these drug–enzyme complexes, with the Avacopan–urease complex exhibiting the highest stability based on RMSD and binding free energy analyses. Natamycin and Avacopan were subsequently selected for in vitro validation, where both significantly inhibited urease activity and demonstrated antibacterial effects against clinical isolates and the reference strain H. pylori B128. Avacopan exhibited inhibition ranging from 30.0% in strain CL2 to 99.7% in B128, whereas Natamycin showed consistently stronger inhibition across all clinical strains, ranging from 89.2% in CL4 to 99.9% in CL1, and exceeding 90% in CL1, CL2, CL3, and B128. Both inhibitors were effective against cag-positive and cag-negative clinical isolates, indicating broad-spectrum urease inhibition. However, the bactericidal activities of these compounds were more strain-specific with increased efficacies observed in cag− isolates. Therefore, further studies are warranted to fully explore the specific mechanisms and selectivity of their individual inhibitory activities. These findings highlight Avacopan and Natamycin as promising urease-targeted drug repurposing candidates for future therapeutic development against H. pylori.
{"title":"Drug Repurposing Identifies Natamycin and Avacopan as Urease-Targeted Therapeutic Candidates Against Helicobacter pylori","authors":"Shwetlaxmi Patil, Sohinee Sarkar, Renitta Jobby, Songmin Yu, Abhishek Chowdhury, Atanuka Paul, Vipin Kumar Mishra, Vinothkannan Ravichandran","doi":"10.1111/hel.70094","DOIUrl":"10.1111/hel.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>The global rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections, including those caused by <i>Helicobacter pylori</i>. This study investigates potential inhibitors of the <i>H. pylori</i> urease enzyme, a key virulence factor that enables survival in the highly acidic gastric environment. A virtual screening of 1773 FDA-approved drugs was performed, followed by molecular dynamics simulations. Among the top candidates, Natamycin, Zavegepant, Midostaurin, Avacopan, and Metolazone displayed significant binding affinities towards urease. Further simulations confirmed the stability and favorable interaction profiles of these drug–enzyme complexes, with the Avacopan–urease complex exhibiting the highest stability based on RMSD and binding free energy analyses. Natamycin and Avacopan were subsequently selected for in vitro validation, where both significantly inhibited urease activity and demonstrated antibacterial effects against clinical isolates and the reference strain <i>H. pylori</i> B128. Avacopan exhibited inhibition ranging from 30.0% in strain CL2 to 99.7% in B128, whereas Natamycin showed consistently stronger inhibition across all clinical strains, ranging from 89.2% in CL4 to 99.9% in CL1, and exceeding 90% in CL1, CL2, CL3, and B128. Both inhibitors were effective against <i>cag</i>-positive and <i>cag</i>-negative clinical isolates, indicating broad-spectrum urease inhibition. However, the bactericidal activities of these compounds were more strain-specific with increased efficacies observed in <i>cag</i><sup>−</sup> isolates. Therefore, further studies are warranted to fully explore the specific mechanisms and selectivity of their individual inhibitory activities. These findings highlight Avacopan and Natamycin as promising urease-targeted drug repurposing candidates for future therapeutic development against <i>H. pylori</i>.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bojan Tepeš, Tatjana Kofol Bric, Mitja Oblak, Jernej Završnik, Helena Blažun Vošner, Danute Ražuka-Ebela, Mārcis Leja, Viktoria Knaze, Jin Young Park, Tamara Matysiak-Budnik
Background
Most gastric cancer cases are attributable to chronic Helicobacter pylori (H. pylori) infection and can theoretically be prevented. The objectives of the EUROHELICAN project were to assess the feasibility, acceptability, effectiveness, and adverse events of the H. pylori screen-and-treat program in younger adults aged 30 to 34 years, for the first time in Europe; to evaluate long-term effects of H. pylori eradication in middle-aged adults (starting from 45 years of age) previously enrolled for at least 5 years in the GISTAR study in Latvia, and to prepare the IARC expert Working Group Report on population-based H. pylori screen-and-treat strategies for gastric cancer prevention.
Methods
The study of H. pylori screen-and-treat in younger adults was conducted in the Community Healthcare Center Dr. Adolf Drolc Maribor following methodology prepared by the National Institute of Public Health of Slovenia. Assessment of possible effects of H. pylori screen-and-treat in the long term was conducted by following up on the long-running GISTAR study conducted by the Institute of Clinical and Preventive Medicine at the University of Latvia. A team of experts led by the Nantes University Hospital evaluated the study protocols and their progress at different stages. The IARC convened a Working Group of international experts to develop globally applicable guidance on best practices for implementing population-based H. pylori screen-and-treat strategies in adult populations to prevent gastric cancer.
Conclusions
Both studies received a positive evaluation at different stages of completion and were deemed appropriate for testing the feasibility of H. pylori screen-and-treat in a community health care setting and investigating possible adverse effects of the strategy in the long-term. The IARC expert group guidance report on the implementation of population-based H. pylori screen-and-treat strategies to prevent gastric cancer in adults will guide future primary gastric cancer prevention programs in Europe and beyond.
背景：大多数胃癌病例可归因于慢性幽门螺杆菌感染，理论上是可以预防的。EUROHELICAN项目的目的是在欧洲首次评估30至34岁年轻人幽门螺杆菌筛查和治疗项目的可行性、可接受性、有效性和不良事件；评估先前在拉脱维亚参加了至少5年GISTAR研究的中年人（45岁起）根除幽门螺杆菌的长期效果，并编写IARC专家工作组关于以人群为基础的幽门螺杆菌筛查和治疗策略用于胃癌预防的报告。方法：在社区卫生保健中心Dr. Adolf Drolc Maribor按照斯洛文尼亚国家公共卫生研究所制定的方法对年轻人进行幽门螺杆菌筛查和治疗研究。通过跟踪拉脱维亚大学临床和预防医学研究所进行的长期GISTAR研究，对幽门螺杆菌筛查和治疗的长期可能影响进行了评估。由南特大学医院领导的一个专家小组评估了研究方案及其在不同阶段的进展。国际癌症研究机构召集了一个国际专家工作组，就在成人人群中实施基于人群的幽门螺杆菌筛查和治疗策略以预防胃癌制定全球适用的最佳实践指南。结论：两项研究在完成的不同阶段都获得了积极的评价，被认为适合于在社区卫生保健环境中测试幽门螺杆菌筛查和治疗的可行性，并调查该策略在长期内可能产生的不良影响。IARC专家组关于实施以人群为基础的幽门螺杆菌筛查和治疗策略以预防成人胃癌的指导报告将指导欧洲及其他地区未来的原发性胃癌预防项目。
{"title":"EUROHELICAN—Accelerating Gastric Cancer Reduction Through Helicobacter pylori Eradication","authors":"Bojan Tepeš, Tatjana Kofol Bric, Mitja Oblak, Jernej Završnik, Helena Blažun Vošner, Danute Ražuka-Ebela, Mārcis Leja, Viktoria Knaze, Jin Young Park, Tamara Matysiak-Budnik","doi":"10.1111/hel.70097","DOIUrl":"10.1111/hel.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Most gastric cancer cases are attributable to chronic <i>Helicobacter pylori (H. pylori)</i> infection and can theoretically be prevented. The objectives of the EUROHELICAN project were to assess the feasibility, acceptability, effectiveness, and adverse events of the <i>H. pylori</i> screen-and-treat program in younger adults aged 30 to 34 years, for the first time in Europe; to evaluate long-term effects of <i>H. pylori</i> eradication in middle-aged adults (starting from 45 years of age) previously enrolled for at least 5 years in the GISTAR study in Latvia, and to prepare the IARC expert Working Group Report on population-based <i>H. pylori</i> screen-and-treat strategies for gastric cancer prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study of <i>H. pylori</i> screen-and-treat in younger adults was conducted in the Community Healthcare Center Dr. Adolf Drolc Maribor following methodology prepared by the National Institute of Public Health of Slovenia. Assessment of possible effects of <i>H. pylori</i> screen-and-treat in the long term was conducted by following up on the long-running GISTAR study conducted by the Institute of Clinical and Preventive Medicine at the University of Latvia. A team of experts led by the Nantes University Hospital evaluated the study protocols and their progress at different stages. The IARC convened a Working Group of international experts to develop globally applicable guidance on best practices for implementing population-based <i>H. pylori</i> screen-and-treat strategies in adult populations to prevent gastric cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Both studies received a positive evaluation at different stages of completion and were deemed appropriate for testing the feasibility of <i>H. pylori</i> screen-and-treat in a community health care setting and investigating possible adverse effects of the strategy in the long-term. The IARC expert group guidance report on the implementation of population-based <i>H. pylori</i> screen-and-treat strategies to prevent gastric cancer in adults will guide future primary gastric cancer prevention programs in Europe and beyond.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anja Šterbenc, Bor Vratanar, Eva Miler Mojškerc, Matjaž Homan
Background
To achieve eradication rates > 90%, the ESPGHAN/NASPGHAN guidelines for pediatric Helicobacter pylori infection recommend tailored antimicrobial therapy using sufficiently high doses over 10–14 days. However, prolonged treatment often leads to suboptimal compliance in children, which is a major contributor to reduced eradication rates. To address this, we evaluated the efficacy and safety of a shorter, 7 day triple therapy with bismuth compared with the 14 day standard triple therapy without bismuth in H. pylori infected children.
Materials and Methods
From 2020 to 2024, we carried out a randomized controlled trial involving treatment-naïve children and adolescents (5–18 years old) with confirmed H. pylori infection. Eligible participants were randomly allocated to receive either a 7 day triple therapy with bismuth (bismuth subcitrate, a proton pump inhibitor [PPI], amoxicillin, plus clarithromycin/metronidazole) or a 14 day standard triple therapy (a PPI, amoxicillin, plus clarithromycin/metronidazole) without bismuth. Two months after completing therapy, treatment success was determined using either a two-step monoclonal stool antigen assay or a urea breath test. Any adverse events were documented using a structured questionnaire.
Results
Seventy-three children were enrolled in the study. In the intention-to-treat analysis, eradication was achieved in 91% of children treated with the 7 day triple therapy with bismuth and 87% of those receiving the 14 day standard triple therapy (p = 0.695). Per-protocol eradication rates were 94% and 87%, respectively (p = 0.418). No serious adverse events were reported, and most adverse events were mild to moderate. A metallic taste was significantly more frequent in the 14 day standard triple therapy group, while other adverse events occurred with similar frequency.
Conclusions
Adding bismuth to a 7 day triple regimen achieved high eradication rates and a safety profile similar to 14 day standard triple therapy, supporting its use as an effective and safe treatment option for pediatric H. pylori infection.
{"title":"An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of a 7-Day Triple Therapy With Bismuth Versus 14-Day Standard Triple Therapy for Helicobacter pylori Eradication in Children and Adolescents","authors":"Anja Šterbenc, Bor Vratanar, Eva Miler Mojškerc, Matjaž Homan","doi":"10.1111/hel.70103","DOIUrl":"https://doi.org/10.1111/hel.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To achieve eradication rates > 90%, the ESPGHAN/NASPGHAN guidelines for pediatric <i>Helicobacter pylori</i> infection recommend tailored antimicrobial therapy using sufficiently high doses over 10–14 days. However, prolonged treatment often leads to suboptimal compliance in children, which is a major contributor to reduced eradication rates. To address this, we evaluated the efficacy and safety of a shorter, 7 day triple therapy with bismuth compared with the 14 day standard triple therapy without bismuth in <i>H. pylori</i> infected children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>From 2020 to 2024, we carried out a randomized controlled trial involving treatment-naïve children and adolescents (5–18 years old) with confirmed <i>H. pylori</i> infection. Eligible participants were randomly allocated to receive either a 7 day triple therapy with bismuth (bismuth subcitrate, a proton pump inhibitor [PPI], amoxicillin, plus clarithromycin/metronidazole) or a 14 day standard triple therapy (a PPI, amoxicillin, plus clarithromycin/metronidazole) without bismuth. Two months after completing therapy, treatment success was determined using either a two-step monoclonal stool antigen assay or a urea breath test. Any adverse events were documented using a structured questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-three children were enrolled in the study. In the intention-to-treat analysis, eradication was achieved in 91% of children treated with the 7 day triple therapy with bismuth and 87% of those receiving the 14 day standard triple therapy (<i>p</i> = 0.695). Per-protocol eradication rates were 94% and 87%, respectively (<i>p</i> = 0.418). No serious adverse events were reported, and most adverse events were mild to moderate. A metallic taste was significantly more frequent in the 14 day standard triple therapy group, while other adverse events occurred with similar frequency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adding bismuth to a 7 day triple regimen achieved high eradication rates and a safety profile similar to 14 day standard triple therapy, supporting its use as an effective and safe treatment option for pediatric <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olga P Nyssen, Guillermo J Ortega, Laimas Jonaitis, Ángeles Pérez-Aísa, Bojan Tepes, Alfredo J Lucendo, Javier Tejedor-Tejada, Renate Bumane, Ana Garre, Jose M Huguet, Monica Perona, Óscar Núñez, Manuel Pabón-Carrasco, Manuel Castro-Fernández, Miguel Areia, Jesús Barrio, Antonio Moreno Loro, Thomas J Butler, María Soledad Marcos, Alma Keco-Huerga, Manuel Domínguez Cajal, Maja Denkovski, Matteo Pavoni, György Miklós Buzás, Frode Lerang, Giuseppe Losurdo, Pablo M Wolfe García, Perminder S Phull, Samuel J Martínez-Domínguez, Juozas Kupcinskas, Mārcis Leja, Ricardo Marcos-Pinto, Sinead M Smith, Antonio Gasbarrini, Veronika Papp, Blas José Gómez Rodríguez, Mónica Sánchez Alonso, Ramón Pajares Villarroya, Pilar Pazo Mejide, Manuel Jiménez-Moreno, Marta Pascual-Mato, Concepción Bravo-Pache, Milagrosa Montes, Anna Cano-Català, Pablo Parra, Leticia Moreira, Francis Mégraud, Colm O'Morain, Luis Bujanda, Javier P Gisbert
Background and aims: Previous antibiotic use influences Helicobacter pylori antibiotic resistance. This study evaluated how prior population-level macrolide (especially clarithromycin) use affects H. pylori eradication success in naïve patients.
Methods: Retrospective, multicenter, ecological study. Multivariate logistic regression was performed with modified intention-to-treat effectiveness as the main outcome. Key variables included first-line clarithromycin-based treatments, therapy duration (7, 10, 14 days), proton pump inhibitor dose (low, standard, high), compliance (> 90%), and clarithromycin consumption (defined daily doses/1000 inhabitants/day, from the European Surveillance of Antimicrobial Consumption Network). Nested hierarchical models incorporated macrolide consumption, matched by year and country, and assessed the interaction between consumption and first-line empirical treatments from the European Registry on H. pylori Management (Hp-EuReg).
Results: The study included 27,549 naïve patients from 23 countries with macrolide consumption data from 2013 to 2022. Higher macrolide consumption, within 0 to 8 years before treatment, was associated with reduced treatment effectiveness. The eradication rate consistently decreased as macrolide consumption increased, particularly within the previous 4 years. The efficacy of triple-clarithromycin-metronidazole, triple-clarithromycin-amoxicillin, and some bismuth-quadruple therapies containing clarithromycin decreased with higher macrolide consumption. At the country level, higher population consumption of clarithromycin 2 years before treatment was associated with a decrease in eradication rates from 93% to 82%.
Conclusion: Higher macrolide consumption in the general population negatively impacts the effectiveness of first-line H. pylori regimens. These findings support that clarithromycin should only be administered as a susceptibility-based therapy, with the strongest negative impact of prior population-level exposure observed within 5 years and diminishing thereafter. ClincialTrials.gov number, NCT02328131.
{"title":"Long-Term Effect of Macrolides on Helicobacter pylori Eradication: Data From the European Registry on Helicobacter pylori Management (Hp-EuReg).","authors":"Olga P Nyssen, Guillermo J Ortega, Laimas Jonaitis, Ángeles Pérez-Aísa, Bojan Tepes, Alfredo J Lucendo, Javier Tejedor-Tejada, Renate Bumane, Ana Garre, Jose M Huguet, Monica Perona, Óscar Núñez, Manuel Pabón-Carrasco, Manuel Castro-Fernández, Miguel Areia, Jesús Barrio, Antonio Moreno Loro, Thomas J Butler, María Soledad Marcos, Alma Keco-Huerga, Manuel Domínguez Cajal, Maja Denkovski, Matteo Pavoni, György Miklós Buzás, Frode Lerang, Giuseppe Losurdo, Pablo M Wolfe García, Perminder S Phull, Samuel J Martínez-Domínguez, Juozas Kupcinskas, Mārcis Leja, Ricardo Marcos-Pinto, Sinead M Smith, Antonio Gasbarrini, Veronika Papp, Blas José Gómez Rodríguez, Mónica Sánchez Alonso, Ramón Pajares Villarroya, Pilar Pazo Mejide, Manuel Jiménez-Moreno, Marta Pascual-Mato, Concepción Bravo-Pache, Milagrosa Montes, Anna Cano-Català, Pablo Parra, Leticia Moreira, Francis Mégraud, Colm O'Morain, Luis Bujanda, Javier P Gisbert","doi":"10.1111/hel.70107","DOIUrl":"https://doi.org/10.1111/hel.70107","url":null,"abstract":"<p><strong>Background and aims: </strong>Previous antibiotic use influences Helicobacter pylori antibiotic resistance. This study evaluated how prior population-level macrolide (especially clarithromycin) use affects H. pylori eradication success in naïve patients.</p><p><strong>Methods: </strong>Retrospective, multicenter, ecological study. Multivariate logistic regression was performed with modified intention-to-treat effectiveness as the main outcome. Key variables included first-line clarithromycin-based treatments, therapy duration (7, 10, 14 days), proton pump inhibitor dose (low, standard, high), compliance (> 90%), and clarithromycin consumption (defined daily doses/1000 inhabitants/day, from the European Surveillance of Antimicrobial Consumption Network). Nested hierarchical models incorporated macrolide consumption, matched by year and country, and assessed the interaction between consumption and first-line empirical treatments from the European Registry on H. pylori Management (Hp-EuReg).</p><p><strong>Results: </strong>The study included 27,549 naïve patients from 23 countries with macrolide consumption data from 2013 to 2022. Higher macrolide consumption, within 0 to 8 years before treatment, was associated with reduced treatment effectiveness. The eradication rate consistently decreased as macrolide consumption increased, particularly within the previous 4 years. The efficacy of triple-clarithromycin-metronidazole, triple-clarithromycin-amoxicillin, and some bismuth-quadruple therapies containing clarithromycin decreased with higher macrolide consumption. At the country level, higher population consumption of clarithromycin 2 years before treatment was associated with a decrease in eradication rates from 93% to 82%.</p><p><strong>Conclusion: </strong>Higher macrolide consumption in the general population negatively impacts the effectiveness of first-line H. pylori regimens. These findings support that clarithromycin should only be administered as a susceptibility-based therapy, with the strongest negative impact of prior population-level exposure observed within 5 years and diminishing thereafter. ClincialTrials.gov number, NCT02328131.</p>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"31 1","pages":"e70107"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kavinda Tissera, Ashansa Ramanayake, Myeong-A Kim, Eui-Jeong Noh, Sacheera Angulmaduwa, Dowon Seo, Yong-Joon Cho, Jeong-Heon Cha
<div> <section> <h3> Introduction</h3> <p>The virulence factor CagA is critical in mediating inflammation, and <i>Helicobacter pylori</i> PMSS1 dynamically modulates <i>cagA</i> copy number in response to host immune pressure. Co-infection with <i>Salmonella enterica serotype Typhimurium</i> has been shown to heighten systemic inflammation and reduce <i>H. pylori</i> colonization while maintaining type IV secretion system functionality. This suggests that the inflammatory environments induced by co-infection may influence <i>H. pylori</i> virulence mechanisms. This study investigates whether <i>H. pylori</i> PMSS1 regulates its <i>cagA</i> copy number during systemic co-infection in a mouse model.</p> </section> <section> <h3> Methods</h3> <p>Across three independent mouse experiments, <i>H. pylori</i> isolated from control and co-infected mice was analyzed for <i>cagA</i> gene copy number using quantitative real-time polymerase chain reaction. Three isolates with the highest <i>cagA</i> copy numbers observed to date were further characterized for their virulence phenotypes and subjected to whole-genome sequencing to identify the mutations associated with co-infection.</p> </section> <section> <h3> Results</h3> <p><i>H. pylori</i> isolates recovered from the stomachs of co-infected mice exhibited significantly higher <i>cagA</i> copy numbers than those from control mice, with the mean copy number increasing from 2.64 (±1.03) in the control group to 3.22 (±1.63) in the co-infected group. Three <i>H. pylori</i> isolates with high <i>cagA</i> copy numbers (6.1, 9.1, and 11.0 copies) were assessed for virulence features. Notably, two of these isolates maintained elevated <i>cagA</i> phosphorylation and cell elongation, suggesting their potential relevance as a model for <i>H. pylori</i> infection studies in mice. Whole-genome sequencing further revealed co-infection-associated nonsynonymous mutations, notably in the <i>fur</i> gene and membrane transport-related genes such as an MFS transporter and a corrinoid ABC transporter substrate-binding protein.</p> </section> <section> <h3> Conclusions</h3> <p>These findings suggest that co-infection with <i>S.</i> promotes an increase in the <i>cagA</i> copy number, thereby enhancing the virulence potential of <i>H. pylori</i>. The study highlights the complex interplay between <i>H. pylori</i> and co-infecting pathogens and their combined impact on <i>H. pylori</i>-mediated disease, and the utility of high-<i>cagA</i> copy isolates as valuable models for in vivo studies addressing pathogenesis.</p>
{"title":"Expansion of cagA Copy Number in Helicobacter pylori During Co-Infection in a Mouse Model","authors":"Kavinda Tissera, Ashansa Ramanayake, Myeong-A Kim, Eui-Jeong Noh, Sacheera Angulmaduwa, Dowon Seo, Yong-Joon Cho, Jeong-Heon Cha","doi":"10.1111/hel.70091","DOIUrl":"10.1111/hel.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The virulence factor CagA is critical in mediating inflammation, and <i>Helicobacter pylori</i> PMSS1 dynamically modulates <i>cagA</i> copy number in response to host immune pressure. Co-infection with <i>Salmonella enterica serotype Typhimurium</i> has been shown to heighten systemic inflammation and reduce <i>H. pylori</i> colonization while maintaining type IV secretion system functionality. This suggests that the inflammatory environments induced by co-infection may influence <i>H. pylori</i> virulence mechanisms. This study investigates whether <i>H. pylori</i> PMSS1 regulates its <i>cagA</i> copy number during systemic co-infection in a mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Across three independent mouse experiments, <i>H. pylori</i> isolated from control and co-infected mice was analyzed for <i>cagA</i> gene copy number using quantitative real-time polymerase chain reaction. Three isolates with the highest <i>cagA</i> copy numbers observed to date were further characterized for their virulence phenotypes and subjected to whole-genome sequencing to identify the mutations associated with co-infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>H. pylori</i> isolates recovered from the stomachs of co-infected mice exhibited significantly higher <i>cagA</i> copy numbers than those from control mice, with the mean copy number increasing from 2.64 (±1.03) in the control group to 3.22 (±1.63) in the co-infected group. Three <i>H. pylori</i> isolates with high <i>cagA</i> copy numbers (6.1, 9.1, and 11.0 copies) were assessed for virulence features. Notably, two of these isolates maintained elevated <i>cagA</i> phosphorylation and cell elongation, suggesting their potential relevance as a model for <i>H. pylori</i> infection studies in mice. Whole-genome sequencing further revealed co-infection-associated nonsynonymous mutations, notably in the <i>fur</i> gene and membrane transport-related genes such as an MFS transporter and a corrinoid ABC transporter substrate-binding protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that co-infection with <i>S.</i> promotes an increase in the <i>cagA</i> copy number, thereby enhancing the virulence potential of <i>H. pylori</i>. The study highlights the complex interplay between <i>H. pylori</i> and co-infecting pathogens and their combined impact on <i>H. pylori</i>-mediated disease, and the utility of high-<i>cagA</i> copy isolates as valuable models for in vivo studies addressing pathogenesis.</p>\u0000 ","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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