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. 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. 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. 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.

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. 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. 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. 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. 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.

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. 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. 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.

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.

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. 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). 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%. 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.

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 invitro 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.

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. 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. 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. Keverprazan 20 mg twice daily with high-dose amoxicillin demonstrates a noninferior efficacy to bismuth quadruple therapy for initial H. pylori eradication. Chinese Clinical Trial Registry, registration No: ChiCTR2400092511.

ABSTRACTBackgroundTo 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 MethodsFrom 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.ResultsSeventy‐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.ConclusionsAdding 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.

ABSTRACTBackgroundTegoprazan, a potassium‐competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.AimThis 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.MethodsThis 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.ResultsOf 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.ConclusionTegoprazan‐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.Trial RegistrationClinicalTrials.gov identifier: NCT05933031