{
  "abstract": "Background Approximately 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. Methods A 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. Results Among 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. Conclusions Multidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 51,
  "authors": [
    {
      "name": "Elise Mitri"
    },
    {
      "name": "Luke Fletcher"
    },
    {
      "name": "Sara Vogrin"
    },
    {
      "name": "Sara Barnes"
    },
    {
      "name": "Neil Powell"
    },
    {
      "name": "Jonny Peter"
    },
    {
      "name": "Philip Kam-Tao Li"
    },
    {
      "name": "Ana Maria Copaescu"
    },
    {
      "name": "Nicholas Turner"
    },
    {
      "name": "Fiona James"
    },
    {
      "name": "Camille Paynter"
    },
    {
      "name": "Richard Sullivan"
    },
    {
      "name": "Maryam Sherkat Masoum"
    },
    {
      "name": "Matthew Rawlins"
    },
    {
      "name": "Geoff Mackay"
    },
    {
      "name": "Benjamin Smith"
    },
    {
      "name": "Patricia Kilfoyle"
    },
    {
      "name": "Daniel Forster"
    },
    {
      "name": "Morgan Rose"
    },
    {
      "name": "Raquel Cowan"
    },
    {
      "name": "Kylie Alcorn"
    },
    {
      "name": "Anna Brischetto"
    },
    {
      "name": "Andrew Mahony"
    },
    {
      "name": "Andrew Redmond"
    },
    {
      "name": "Arindam Chakravorty"
    },
    {
      "name": "Zaal Meher-Homji"
    },
    {
      "name": "Chino Yuson"
    },
    {
      "name": "Simeon Crawford"
    },
    {
      "name": "Greg Weeks"
    },
    {
      "name": "Sasheela Sri La Sri Ponnampalavanar"
    },
    {
      "name": "Constance Katelaris"
    },
    {
      "name": "Priscilla Tran"
    },
    {
      "name": "Jennifer O'Hern"
    },
    {
      "name": "Jack Godsell"
    },
    {
      "name": "Trisha Peel"
    },
    {
      "name": "Indy Sandaradura"
    },
    {
      "name": "David New"
    },
    {
      "name": "Candice Holland"
    },
    {
      "name": "Tim Cutfield"
    },
    {
      "name": "Sarah Coghill"
    },
    {
      "name": "Caitlin Hand"
    },
    {
      "name": "Jacob Williams"
    },
    {
      "name": "Jaclyn Bishop"
    },
    {
      "name": "Belinda Lambros"
    },
    {
      "name": "Cascia Day"
    },
    {
      "name": "Courtney Ierano"
    },
    {
      "name": "Jason A. Roberts"
    },
    {
      "name": "Natasha Holmes"
    },
    {
      "name": "Marlena Klaic"
    },
    {
      "name": "Suran Fernando"
    },
    {
      "name": "Jason Trubiano"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eddtr5wwta970.bib",
  "cited_by": 5,
  "doi": "10.1093/cid/ciag082",
  "fulltext_url": null,
  "id": "eddtr5wwta970",
  "issns": [
    "1058-4838",
    "1537-6591"
  ],
  "landing_url": "https://hal.science/hal-05834749v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "openalex",
      "2736|Drug-Induced Adverse Reactions"
    ]
  ],
  "openalex": "W7147646993",
  "pdf_url": "https://hal.science/hal-05834749/document",
  "pmcid": null,
  "pmid": "41921035",
  "published": "2026-06-15",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/eddtr5wwta970.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:00Z",
      "native_id": "hal-05834749",
      "source": "hal",
      "url": "https://hal.science/hal-05834749v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Drug-Induced Adverse Reactions",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Direct Oral Challenge for Penicillin Allergy: The International Network of Antibiotic Allergy Nations (iNAAN) Study",
  "title_text": "Direct Oral Challenge for Penicillin Allergy: The International Network of Antibiotic Allergy Nations (iNAAN) Study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:00Z",
  "url": "https://research.draconitic.com/paper/eddtr5wwta970",
  "venue": "Clinical Infectious Diseases",
  "versions": []
}