{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:56Z","timestamp":1787027516637,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Mohammed VI des Sciences et de la Sant\u00e9"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background and Aims: Amoxicillin is one of the most effective antibiotics for treating Helicobacter\u00a0pylori infections and is widely used in first-line treatment regimens. However, patients with penicillin allergies cannot receive penicillin-based therapies, which significantly limits effective eradication options. This allergy often compels clinicians to choose alternative regimens that may be less effective, thereby increasing the risk of treatment failure. Consequently, therapeutic options for these patients are more restricted, and clinicians must carefully select the most appropriate regimen, taking into account both efficacy and the potential for antimicrobial resistance. This review aims to systematically evaluate the efficacy of penicillin-free treatment regimens for the eradication of H.\u00a0pylori in patients with penicillin allergies. Specifically, it seeks to identify, analyze, and synthesize current clinical evidence to determine the most effective alternative therapies, thereby supporting evidence-based clinical decision-making. Methods: A literature search was conducted using the PubMed and Scopus databases. We began by reviewing the titles and abstracts of all identified studies to determine eligibility. Next, we assessed the full text of potentially eligible articles according to inclusion and exclusion criteria to establish the eligibility of each study. Results: This review included 26 studies comprising 2713 participants, evaluating penicillin-free therapies for H.\u00a0pylori eradication in penicillin-allergic patients. Key findings demonstrated high eradication rates with bismuth-based quadruple therapies (88\u201397%), doxycycline-based regimens (86%), and quinolone-based therapies (75\u2013100%), with Sitafloxacin exceeding 90% efficacy. Minocycline-based regimens also showed promising outcomes, with eradication rates between 80% and 85%. Although the PPI\u2013clarithromycin\u2013metronidazole combination was moderately effective, it was less favored as a first-line option. Overall, bismuth-based and quinolone-based therapies emerged as the most effective alternatives. Conclusions: In patients allergic to penicillin, bismuth quadruple therapy has demonstrated an excellent rate of eradication. Quinolone-based regimens are emerging as a promising alternative in first-line treatment or in cases of treatment failure. Vonoprazan-based therapy is an effective regimen. Combined with clarithromycin and metronidazole, vonoprazan enhances eradication rates and demonstrates effectiveness, including in clarithromycin-resistant strains.<\/jats:p>","DOI":"10.3390\/antibiotics14050476","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:47:15Z","timestamp":1746686835000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Kenza","family":"El Boury","sequence":"first","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4409-5256","authenticated-orcid":false,"given":"Hind","family":"Boudarf","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"},{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane","family":"Adoud","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"},{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soukaina","family":"Ouannass","sequence":"additional","affiliation":[{"name":"Research 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Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-9092","authenticated-orcid":false,"given":"Fatima Azzahra","family":"Lahlou","sequence":"additional","affiliation":[{"name":"Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-1535","authenticated-orcid":false,"given":"Samy","family":"Iskandar","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryem","family":"El Jemli","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-2294","authenticated-orcid":false,"given":"Idrissa","family":"Diawara","sequence":"additional","affiliation":[{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"},{"name":"Laboratory of Microbial Biotechnology and Infectiology Research, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Amine","family":"Senhaji","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lhousaine","family":"Balouch","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"},{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0115-682X","authenticated-orcid":false,"given":"Zakaria","family":"Belrhiti","sequence":"additional","affiliation":[{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"},{"name":"Mohammed VI International School of Public Health, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Kettani Halabi","sequence":"additional","affiliation":[{"name":"Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco"},{"name":"Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco"},{"name":"Mohammed VI Faculty of Medicine, Mohammed VI 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