In a prospective single-center cohort from Portugal (2013–2024; n=591), concomitant quadruple therapy (QuadC) and bismuth quadruple therapy (QuadB) achieved Helicobacter pylori eradication rates of 92.9% and 90.4%, respectively, on intention-to-treat analysis, significantly outperforming standard triple therapy at 73.9%. Sequential quadruple therapy (QuadS) achieved 84.2%, with no significant difference versus QuadC or QuadB.

Participants were a median 57 years old and 57% were women; most were evaluated for dyspeptic symptoms (61%). Treatment distribution was QuadC 34%, QuadB 33%, triple therapy 23%, and QuadS 10%.

Adverse events (AE) occurred more often with quadruple regimens—reported as ~18% and ~17% for QuadC and QuadB —compared with triple therapy (~6%) or QuadS (~2%). Despite the higher AE burden, overall adherence was 97.1% with no significant differences between regimens.

In multivariable analysis, prior eradication attempts, poor adherence, and absence of statin use independently predicted treatment failure (model AUC was 0.72). The authors noted internal inconsistencies in the confidence intervals, likely due to typesetting errors, though the directional associations were clear.

In a high-prevalence setting where empirical therapy remains common, concomitant and bismuth quadruple regimens provided substantially higher eradication rates than triple therapy without an adherence penalty. Sequential quadruple therapy, achieving ~84% efficacy with fewer AEs, may serve as a reasonable alternative when bismuth is unavailable. These results, presented at UEG Week 2025, support using concomitant or bismuth quadruple therapy as default empiric options in similar settings while emphasizing adherence and careful management after prior failures. 

Disclosures: The authors report no conflicts of interest.