Quadruple therapies show a higher eradication rate compared to standard triple therapy for <i>Helicobacter pylori</i> infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries

<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Gastric cancer (GC) is one of the most lethal malignancies worldwide. <jats:italic>Helicobacter pylori</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> 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 <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and <jats:italic>CYP2C19</jats:italic> polymorphisms.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>772 patients were incorporated (64.64% females; mean age of 52.93 years). The total <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> 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 (<jats:italic>p</jats:italic>: &lt;0.05); and 1.24 (<jats:italic>p</jats:italic>: &lt;0.05), respectively. The antibiotic‐resistance prevalence by country, but not the prevalence of <jats:italic>CYP2C19</jats:italic> polymorphism, showed a statistically significant impact on eradication success.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Both QCT and QBT are superior to STT for <jats:italic>H</jats:italic>. <jats:italic>pylori</jats:italic> eradication when adjusted for country‐specific antibiotic resistance and <jats:italic>CYP2C19</jats:italic> polymorphism in a sample of individuals residing in five countries within two continents.</jats:p></jats:sec>