Helicobacter pylori retreatment: When clinical guidelines meet patient reality

Table 1 Key advances, unresolved controversies, and practical implications in post-failure Helicobacter pylori management

Field	Current advance	Remaining controversy	Practical implication
Treatment strategy	Rescue treatment has moved beyond legacy triple therapy and now includes optimized bismuth quadruple regimens, rifabutin-containing options, and vonoprazan-based regimens[8,9,14,30,33]	The point at which empiric rescue should give way to susceptibility-guided therapy remains uncertain[8,25,38]	Document previous antibiotic exposure carefully and avoid reusing combinations that are unlikely to remain effective
Resistance testing	Culture-based and molecular/genotypic resistance-guided approaches are increasingly supported by comparative studies and reflected in contemporary guidelines[8,34,35,73]	Access to testing remains uneven, and waiting for susceptibility data may delay retreatment in routine practice	Use tailored therapy when testing is available, but do not let lack of testing lead to therapeutic inertia
Older patients	Age alone is increasingly recognized as an imprecise surrogate for treatment capacity[17,54]	How best to weigh long-term preventive benefit against frailty, polypharmacy, and patient preference remains debated	Assess comorbidity, frailty, and goals of care directly rather than relying on chronological cut-offs
Adherence support	Reinforced instructions, reminder systems, and structured education can improve treatment completion and, in some settings, eradication outcomes[65-67]	These interventions remain underused and are rarely incorporated into rescue pathways	Treat adherence support as part of treatment planning rather than as an optional add-on after failure
Program evaluation	Test-of-cure is now widely recognized as essential, but structured tracking after confirmed treatment failure remains underdeveloped[8,9,17,40]	Most quality frameworks still stop short of evaluating what happens after confirmed failure	Include rescue initiation, treatment completion, and confirmatory testing after rescue in quality assessment

Table 2 Proposed structured pathway after confirmed Helicobacter pylori eradication failure

Steps	Clinical questions	Suggested action
Verify failure	Was the test-of-cure performed at the appropriate interval, and off acid suppression or other confounding medications where relevant?	Confirm persistent infection before modifying treatment
Review the prior treatment course	Which drugs were used, for how long, and with what degree of dosing complexity? Were there missed doses, interruptions, or clinically relevant adverse events?	Review the prior regimen, duration, adherence, interruptions, and adverse-event history in detail
Identify the main driver of failure	Is the failure most likely related to resistance, poor adherence, treatment intolerance, or gaps in follow-up?	Define the principal contributors to failure and use this assessment to guide the next step
Choose rescue therapy	What were the previous antibiotic exposures, what is known about local resistance patterns, and are there allergy constraints or access to susceptibility testing?	Select an empiric or susceptibility-guided regimen that avoids likely cross-resistance and is feasible for the patient
Anticipate tolerability issues and support completion	Which symptoms or adverse effects mattered most during prior treatment, and what practical barriers may compromise completion this time?	Provide clear written instructions, anticipatory guidance on adverse events, and practical support to improve treatment completion
Arrange follow-up in advance	When and how will eradication be reassessed, and who will contact the patient if follow-up is missed?	Schedule test-of-cure and follow-up before the patient leaves, ideally with reminder support