Breaking the time barrier in Helicobacter pylori retreatment: Insights from multidimensional perspectives

We read the recent article conducted by Lin et al[1] titled “The interval of rescue treatment does not affect the efficacy and safety of Helicobacter pylori eradication” with great interest. This prospective multicenter study demonstrated that the interval between failed eradication and rescue therapy did not significantly influence eradication rates or safety when 14-day bismuth quadruple therapy was used. These findings challenge conflicting earlier reports[2] and support prompt retreatment without delaying “resetting” bacterial susceptibility. This study included a rigorous design, a large sample size, and the use of low-resistance antibiotics, which likely mitigated resistance-driven failures. Notably, even short intervals (≥4 weeks) achieved comparable efficacy, in contrast to retrospective data that favor delayed therapy. Clinically, these findings reassure clinicians that timely retreatment is safe and effective. However, several considerations merit attention. First, Helicobacter pylori (H. pylori) reexamination was not performed at 6 months after successful eradication to evaluate whether H. pylori recrudescence occurred. H. pylori reinfection occurs over a long-term period (e.g., more than 12 months) after successful eradication.[3] A subset of patients was defined as having successful eradication mainly because of the short-term inhibition of H. pylori; however, there was revival at 6 months, leading to an overestimated eradication rate. To comprehensively evaluate the influence of the interval of rescue treatment on the efficacy of H. pylori, this point should not be ignored, although the recurrence probabilities are very low. Second, the subgroup analyses involved multiple tests without correction (e.g., Bonferroni), increasing false-positive risk. Uncorrected multiple comparisons can lead to a decrease in the credibility of research results, especially when a large number of tests are involved. Third, our previous study revealed that H. pylori eradication induced dysbiosis of the gut microbiota and increased the abundance of antibiotic resistance genes.[4] Compared with triple therapy, bismuth quadruple therapy induced a longer period of perturbation of the gut microbiota.[5] The influence of eradication on the alteration of the gut microbiota was not analyzed in this study, and whether a shorter interval of rescue treatment could induce severe dysbiosis of the gut microbiota remains unclear. In conclusion, Lin et al[1] provided compelling evidence that rescue intervals did not affect outcomes when optimized quadruple regimens were used. The ultimate goal is to reshape the global paradigm of H. pylori treatment by adopting precise, simplified strategies to achieve high efficacy. Funding This study was supported by grants from the National Natural Science Foundation of China (Nos. 82000531 and 82360118). Conflicts of interest None.