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The mismatch matters: patients with a penicillin label receive more second-line and broader-spectrum antibiotics, with measurable downstream costs in infection, surgical site morbidity, length of stay, and antimicrobial resistance. Specialist-led skin testing and graded oral challenge remain the diagnostic standard, but the global allergy workforce cannot test the population that needs testing. Validated decision rules such as PEN-FAST, structured non-allergist pathways, and direct oral challenge in low-risk patients have closed part of that gap, but uptake is still limited by inconsistent free-text documentation, variable clinician confidence, and weak integration with electronic health records. This review summarises how computational methods are being added to that pathway. Supervised machine-learning models can mine electronic health records to identify candidates for review. Natural language processing can recover the timing, character, and severity of a reaction from clinic letters that the structured allergy field omitted. Predictive models that combine clinical, laboratory, and immunological inputs are starting to outperform rule-based scores on beta-lactam risk. Decision-support systems are moving past simple drug-name matching toward context-aware alerts. Image classifiers and large language models are opening a route to rapid, photograph-and-history triage. We discuss what is needed for any of this to be safe in routine care: representative training data, transparent model behaviour, regulatory alignment, and prospective evaluation against the outcomes the antimicrobial stewardship community already measures.<\/jats:p>","DOI":"10.1007\/s12016-026-09203-0","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:44:42Z","timestamp":1790081082000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Approaches to Penicillin Allergy De-labelling: A Clinical Review"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-6795","authenticated-orcid":false,"given":"Shuayb","family":"Elkhalifa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Devey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahaman","family":"Al-Asali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haggar","family":"Elbashir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja Bulatovi\u0107","family":"\u0106alasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick G.","family":"Pleijhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Terreehorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Salvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irfan","family":"Shafiq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Isse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abuzakouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Medhat","family":"Gaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehan","family":"Bhana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"3","key":"9203_CR1","doi-asserted-by":"publisher","first-page":"258263","DOI":"10.1016\/j.jaip.2013.02.002","volume":"1","author":"E Macy","year":"2013","unstructured":"Macy E, Ngor EW (2013) Safely diagnosing clinically significant penicillin allergy using only penicilloyl-polylysine, penicillin, and oral amoxicillin. 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Mayo Clin Proc Digit Health 3(3):100244","journal-title":"Mayo Clin Proc Digit Health"}],"container-title":["Clinical Reviews in Allergy &amp; Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12016-026-09203-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12016-026-09203-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12016-026-09203-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:44:46Z","timestamp":1790081086000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12016-026-09203-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9203"],"URL":"https:\/\/doi.org\/10.1007\/s12016-026-09203-0","relation":{},"ISSN":["1559-0267"],"issn-type":[{"value":"1559-0267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"26 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors have declared no conflict of interest. S Elkhalifa has received funding and served in advisory roles as follows: Funding and Grants: Received funds from Health Education England and Manchester University NHS Foundation Trust for the development of the Drug Allergy App. Advisory Roles: Served as an expert advisor for MTEP\/NICE. Industry Collaborations: Participated in advisory boards, expert consultations, or received travel\/speaking honoraria from AstraZeneca, Sanofi, Novartis, GSK, Biologix, Newbridge, BioCryst, CSL, and Takeda Pharmaceutical Companies. Co-authors at Birmingham City University acknowledge Innovation Seed Funding from the Henderson Family Foundation, which part-funded development of the Drug Allergy 2.0 application. No funder had any role in the design, drafting, or decision to submit this manuscript.","order":1,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"79"}}