A Review on the Progress and Strategies of Helicobacter pylori Eradication Therapy for Patients With Penicillin Allergy

Background Helicobacter pylori (H. pylori) eradication in penicillin‐allergic patients poses a challenge. The currently recommended regimens are inadequate for clinical eradication therapy. Recent years have seen reports of new drugs, regimens, and study evidence in this field; yet comprehensive review articles on the treatment of H. pylori infection in penicillin‐allergic patients are scarce. Methods A literature search of PubMed, Web of Science, Embase, China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wanfang Database up to January 10, 2026, was conducted with the search strategy (“Helicobacter pylori” OR “H. pylori”) AND (“treatment” OR “therapy”) AND (“penicillin” OR “beta‐lactam”) AND (“allergy”, “allergic” OR “anaphylaxis”) for both English and Chinese language publications Results The final literature review included 132 treatment groups from 56 studies in nine different countries or regions, with a total of 5542 patients included in the analyses. The overall eradication rates of triple regimens were unsatisfactory (72.9%, 95% CI 70.7%–75.2%). The classic quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) is commonly recommended due to its relatively satisfactory efficacy and sufficient research evidence (81.4%, 95% CI 78.6%–84.2%). The mean eradication rate for other regimens containing new drugs such as minocycline, cefuroxime, sitafloxacin, vonoprazan, and rifabutin is well (> 80%). Conclusion The classical bismuth quadruple therapy used to be the most commonly used regimen. The overall eradication efficacy of triple therapies is unacceptable. Although new drugs and regimens have emerged, their efficacy needs confirmation through more high‐quality, large‐scale clinical studies to identify the optimal eradication therapy regimen. Individualized treatment, particularly therapies tailored based on the results of genetic antibiotic resistance testing, represents an important direction for future research.