{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:51:01Z","timestamp":1792162261193,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Amoxicillin, alone or combined with clavulanic acid, is widely used for the treatment of bacterial infections. While clavulanic acid expands amoxicillin's antibacterial spectrum by inhibiting \u03b2\u2010lactamases, differences in their real\u2010world safety profiles and reporting patterns remain relevant for pharmacovigilance and antimicrobial surveillance. This study aimed to characterize and compare adverse event reporting associated with amoxicillin and amoxicillin\/clavulanic acid and to explore reporting signals involving Preferred Terms potentially associated with reduced treatment effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adverse drug reaction reports recorded in the FDA Adverse Event Reporting System (FAERS) Public Dashboard between 2022 and 2025 were analyzed. Disproportionality analyses were performed at the MedDRA Preferred Term level using Reporting Odds Ratios, Proportional Reporting Ratios, and Information Component\u2010based methods. Selected Preferred Terms were further evaluated through direct comparison between the two therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Amoxicillin was predominantly associated with hypersensitivity and cutaneous adverse event signals, whereas amoxicillin\/clavulanic acid showed a stronger hepatobiliary reporting profile, including signals for drug\u2010induced liver injury, cholestasis, and hepatic cytolysis. Direct comparison confirmed distinct reporting patterns, with relatively stronger liver\u2010related signals for the combination therapy and stronger hypersensitivity\u2010related signals for amoxicillin alone. Preferred Terms potentially associated with reduced treatment effectiveness or antimicrobial resistance were identified in both groups; however, these reporting signals may reflect heterogeneous clinical scenarios and should not be interpreted as evidence of confirmed therapeutic failure or microbiological resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support the use of pharmacovigilance databases as complementary tools for antibiotic safety monitoring and for identifying reporting patterns that may warrant further investigation, including reports suggestive of reduced treatment effectiveness. However, such signals should be interpreted cautiously, as they do not establish reduced antimicrobial effectiveness or antimicrobial resistance and may reflect a variety of underlying clinical and therapeutic factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.73328","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:17:01Z","timestamp":1791184621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Adverse Event Reporting Patterns of Amoxicillin and Amoxicillin\/Clavulanic Acid in FAERS: A 2022\u20132025 Disproportionality Analysis"],"prefix":"10.1002","volume":"9","author":[{"given":"Pierangela","family":"Irrera","sequence":"first","affiliation":[{"name":"Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ammendolia","sequence":"additional","affiliation":[{"name":"Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Frattima","sequence":"additional","affiliation":[{"name":"Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3431-9421","authenticated-orcid":false,"given":"Fabiola De","family":"Luca","sequence":"additional","affiliation":[{"name":"Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Campolo","sequence":"additional","affiliation":[{"name":"Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina 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 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Ardizzone","sequence":"additional","affiliation":[{"name":"UniCamillus\u2010Saint Camillus International University of Health Sciences Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Dental Sciences and Morpho\u2010Functional Imaging, University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-020-00374-7"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2006.12.014"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42485-024-00135-x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.11.028"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327745"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00047-19"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.2c00369"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15030384"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14060603"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.12659\/AOT.939258"},{"key":"e_1_2_13_12_1","volume-title":"Murray's Basic Medical Microbiology E\u2010Book: Foundations and Cases","author":"Murray P. R.","year":"2023"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.08.028"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hmedic.2025.100401"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2023.15.2.201"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr159"},{"issue":"4","key":"e_1_2_13_17_1","first-page":"139","article-title":"Amoxicillin\u2010Clavulanic Acid Therapy May Be Associated With Severe Side Effects\u2010Review of the Literature","volume":"6","author":"Gresser U.","year":"2001","journal-title":"European Journal of Medical Research"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112664"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-023-00771-8"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30183825"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13050457"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10030420"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.668"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050466"},{"key":"e_1_2_13_27_1","volume-title":"Guide on Methodological Standards in Pharmacoepidemiology","author":"Anes A. M.","year":"2012"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-023-01316-1"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4121-6"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12550"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.15503"}],"container-title":["Health Science Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.73328","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hsr2.73328","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.73328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:29:44Z","timestamp":1792160984000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hsr2.73328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/hsr2.73328"],"URL":"https:\/\/doi.org\/10.1002\/hsr2.73328","archive":["Portico"],"relation":{},"ISSN":["2398-8835","2398-8835"],"issn-type":[{"value":"2398-8835","type":"print"},{"value":"2398-8835","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e73328"}}