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Introduction: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations., Objective: To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America., Methods: A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms., Results: 772 patients were incorporated (64.64% females; mean age of 52.93 years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success., Conclusions: Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Helicobacter pylori (H. pylori) is the primary etiological agent of gastric adenocarcinoma, which affects over 60% of the global population, with a significant prevalence in Latin America. Given its impact on the affected population, it is crucial to understand the diagnostic tools available for detecting this infection. While clarithromycin-based therapies are still widely used, the high rates of resistance to this antibiotic in the region needs the establishment of alternative, more effective treatments as the standard of care, such as bismuth-based quadruple therapy or high-dose dual therapy with amoxicillin. In cases of refractory infection, local data registries are valuable for informed decision-making.