Persistent H. pylori with True Penicillin Allergy After Bismuth Quadruple Therapy Failure

This protocol addresses the next clinical step for treatment-experienced patients with environmental metaplastic atrophic gastritis who have a true penicillin allergy and in whom H. pylori infection persists despite a prior salvage attempt with optimized bismuth quadruple therapy.

Clinical scenario

Patient profile

The patient is treatment-experienced — H. pylori infection has persisted despite at least one prior eradication attempt. A confirmed true penicillin allergy constrains antibiotic selection, ruling out amoxicillin-containing regimens. Salvage therapy refers to any treatment given after initial eradication has failed.

Previous therapy — eradication not confirmed

Why this protocol is needed

The prior salvage course with optimized bismuth quadruple therapy (BQT) — the only recommended salvage regimen for patients with a true penicillin allergy — did not achieve confirmed eradication. The required goal of a negative test of cure at least 4 weeks after completing therapy was not met, necessitating further escalation.

Treatment approach

Partial overview (next-line salvage)

When susceptibility testing confirms a levofloxacin-sensitive H. pylori strain, the protocol involves a susceptibility-guided salvage approach using levofloxacin triple therapy, with antibiotic substitution to accommodate the penicillin allergy. The full regimen composition, sequencing, and eligibility criteria are detailed in the complete structured protocol below.

Treatment goal

Confirmed eradication of H. pylori infection, verified by a test of cure — urea breath test, fecal antigen test, or biopsy-based test — conducted at least 4 weeks after the end of therapy.

Instant Access to Structured Evidence-Based Regimens

References

The umbrella term "salvage therapy" refers to any treatment provided to patients with persistent H. pylori infection despite initial therapy.
Of the recommended and suggested salvage regimens, only optimized BQT is suitable for patients with a true penicillin allergy.
In treatment-experienced patients with persistent H. pylori infection, levofloxacin triple therapy is suggested in patients with known levofloxacin-sensitive H. pylori strains and when optimized bismuth quadruple or rifabutin triple therapies have previously been used or are unavailable (conditional recommendation, low quality of evidence).
Metronidazole should be used in place of amoxicillin for levofloxacin triple therapy in patients with true penicillin allergy.
All patients who are treated for H. pylori infection should undergo a test of cure with an appropriately conducted urea breath test, fecal antigen test, or biopsy-based test at least 4 weeks after completion of therapy.

DOI: 10.14309/ajg.0000000000002968

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