{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:17:49Z","timestamp":1791224269917,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Amoxicillin is widely prescribed, either as a monotherapy or in combination with clavulanic acid, with its therapeutic indications including a broad range of infections. Its combination with clavulanic acid maintains its known activity against strains producing \u03b2-lactamase. There are limited studies on adverse reactions and antibiotic resistance, with researchers relying primarily on databanks that report spontaneous events caused by amoxicillin or the combination of amoxicillin\/clavulanic acid. Antimicrobial resistance is an overlooked adverse event, and pharmacovigilance databases could serve as a tool in tracking resistance. On this basis, a study to define the safety profile of amoxicillin and amoxicillin\/clavulanic acid and to increase the knowledge necessary to support the battle against antimicrobial resistance was undertaken through the analysis of pharmacovigilance databases. Suspected adverse reactions to amoxicillin and to the combination of amoxicillin\/clavulanic acid in the data system EudraVigilance (2020\u20132024) were analyzed. The most frequent alerts concerned \u201cSkin and subcutaneous disorders\u201d for both drugs. Disproportionate analysis of cases concerning \u201cHepatobiliary disorders\u201d or \u201cDrug inefficiency\u201d indicates a significant increase in these alerts with the amoxicillin\/clavulanic acid combination compared to amoxicillin. The amoxicillin\/clavulanic acid combination has previously been associated with a higher risk of hepatotoxicity and antibiotic resistance to amoxicillin\/clavulanic acid; however, this is the first time that a post-marketing surveillance study has shown that antimicrobial resistance is more likely to occur with the combination in comparison to amoxicillin alone.<\/jats:p>","DOI":"10.3390\/molecules30183825","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T11:18:16Z","timestamp":1758539896000},"page":"3825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hepatotoxicity and Antimicrobial Resistance to Amoxicillin and Amoxicillin\/Clavulanic Acid: Data Analysis from EudraVigilance"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-8065","authenticated-orcid":false,"given":"Ilaria","family":"Ammendolia","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-4821","authenticated-orcid":false,"given":"Gioacchino","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaconcetta","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Midiri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-5674","authenticated-orcid":false,"given":"Luigi","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"ref_1","unstructured":"Akhavan, B.J., Khanna, N.R., and Vijhani, P. 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