{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:40:30Z","timestamp":1791405630436,"version":"4.3.3"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council (NHMRC) Emerging Leadership Fellowship","award":["GNT2008071"],"award-info":[{"award-number":["GNT2008071"]}]},{"name":"PhD Scholarship from the Australian Government funded National Allergy Centre of Excellence"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\nBackground<\/jats:title>\nPenicillin allergies are reported in 1 in 10 hospitalised patients globally and are associated with inferior patient and health service outcomes. However, more than 95% of low-risk penicillin allergies can be removed by direct oral challenge (DOC).<\/jats:p>\n<\/jats:sec>\n\nObjective<\/jats:title>\nThe International Network of Antibiotic Allergy Nations (iNAAN) aims to evaluate the utility of an audit and feedback (A&F) and education implementation strategy to increase the adoption of penicillin DOC in patients with a low-risk penicillin allergy, while concurrently assessing the impact of penicillin DOC on antibiotic prescribing and health service outcomes.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nThis is an international, multicentre type 2 hybrid effectiveness-implementation trial evaluating the widespread safety, clinical effectiveness and implementation of penicillin allergy delabeling via DOC, following penicillin allergy assessment using a purpose-built digital penicillin allergy toolkit within a smartphone application. The implementation strategy encompasses evaluation of co-designed digitally delivered bimonthly A&F reports to health services and clinicians, beginning a minimum of three months post site-activation, and optional education sessions that are delivered by the study team. The primary effectiveness outcome is the proportion of patients with a low-risk penicillin allergy that are delabeled following DOC. The primary implementation outcome is clinician adoption of the digital penicillin allergy toolkit within 6-months of site activation. Participants include adult patients who report a penicillin allergy and have undertaken a formalised penicillin allergy assessment, with or without DOC, at a participating health service. A target trial emulation approach will be used to analyse secondary effectiveness outcomes, including the impact of penicillin DOC on international antibiotic prescribing, infection-related and health service outcomes.<\/jats:p>\n<\/jats:sec>\n\nDiscussion<\/jats:title>\nThis study protocol presents a type 2 hybrid effectiveness-implementation trial design that will provide high level evidence to aid widespread implementation of penicillin DOC.<\/jats:p>\n<\/jats:sec>\n\nTrial registration<\/jats:title>\nACTRN12623000484640 (https:\/\/www.anzctr.org.au\/<\/jats:ext-link>) (https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=385815&isReview=true<\/jats:ext-link>).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0330724","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:30:14Z","timestamp":1757093414000},"page":"e0330724","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["International Network of Antibiotic Allergy Nations (iNAAN): Protocol for a type 2 hybrid effectiveness-implementation multicentre prospective cohort and target trial emulation study evaluating penicillin allergy delabeling via direct oral challenge"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1250-2847","authenticated-orcid":true,"given":"Elise A.","family":"Mitri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke 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