Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2026
Direct Oral Challenge for Penicillin Allergy: The International Network of Antibiotic Allergy Nations (iNAAN) Study.
Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Strategies to Increase Equitable Access to Penicillin Allergy Delabeling Interactions: A Qualitative Study.JAMA network open · 2026Article
- Low Risk Is Low Risk: iNAAN Post Hoc Analysis of Phenotypic Predictors of Penicillin Direct Oral Challenge Safety.Allergy · 2026Article
- Direct Oral Challenge for Penicillin Allergy: A Hospital Implementation Evaluation Via the International Network of Antibiotic Allergy Nations (iNAAN) Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
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52 authors.
Funding
Abstract
backgroundApproximately 10% of hospitalized patients globally report a penicillin allergy, leading to inappropriate antibiotic prescribing and inferior healthcare outcomes. Evidence supporting the effectiveness and widespread implementation of inpatient penicillin direct oral challenge (DOC) is limited.
methodsA prospective, multicenter, international type 2 hybrid effectiveness-implementation study was conducted in 40 hospitals across 8 countries between November 2022 and May 2025. Adult inpatients with a penicillin allergy underwent assessment using a digital penicillin allergy toolkit (National Antibiotic Allergy Network [NAAN] App). According to site clinical practice, participants received penicillin DOC (effectiveness intervention) or assessment only. Participating sites received bimonthly audit and feedback at least 3 months after site activation (implementation strategy). Observational data were used to emulate a target trial to examine secondary effectiveness outcomes, including antibiotic prescribing at 90 days in DOC versus non-DOC participants. The primary implementation outcome was adoption of the NAAN App within 6 months of site activation.
resultsAmong 5121 participants assessed, 1573 (30.7%) underwent DOC, of which 1502 (95.5%) were delabeled. Of 71 (4.5%) participants with a positive DOC, 6 (0.4%) had a serious adverse event. Of 1852 inpatients in the target trial analysis, 892 underwent DOC and 960 underwent assessment only. Participants who underwent DOC were more likely to be prescribed penicillin (risk ratio [RR], 13.25 [95% confidence interval {CI}, 7.82-22.46]), and less likely to be prescribed World Health Organization (WHO) "Watch" or "Reserve" antibiotics (RR, 0.73 [95% CI, .60-.89]) at 90 days post evaluation. Within 6 months of site activation, 77 clinicians adopted the NAAN App.
conclusionsMultidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.
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