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Direct Oral Challenge for Penicillin Allergy: The International Network of Antibiotic Allergy Nations (iNAAN) Study

Elise A Mitri1,2,3, Luke R Fletcher4,5,6, Sara Vogrin1,2

  • 1Department of Infectious Diseases and Immunology, Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|April 1, 2026
PubMed

Insights

Inpatient penicillin direct oral challenge (DOC) is safe and effective for penicillin allergy assessment. This method improved penicillin prescribing and reduced the use of restricted antibiotics in hospitalized patients.

Area of Science:

  • Infectious Diseases
  • Clinical Pharmacology
  • Health Services Research

Background:

  • Penicillin allergy is reported by ~10% of hospitalized patients globally, leading to suboptimal antibiotic use and poorer outcomes.
  • Limited evidence exists on the effectiveness and implementation of inpatient penicillin direct oral challenge (DOC).

Purpose of the Study:

  • To evaluate the effectiveness and implementation of an inpatient penicillin DOC strategy.
  • To assess the impact of DOC on antibiotic prescribing patterns.

Main Methods:

  • A prospective, multicenter, international hybrid effectiveness-implementation study involving 40 hospitals.
  • Adult inpatients with penicillin allergy were assessed using the National Antibiotic Allergy Network (NAAN) App and underwent DOC or assessment only.
  • Audit and feedback were provided to sites, and observational data emulated a target trial.

Main Results:

  • Of 5121 assessed, 1573 underwent DOC, with 95.5% successfully delabeled.
  • DOC participants were more likely to receive penicillin (RR 13.25) and less likely to receive WHO "Watch" or "Reserve" antibiotics (RR 0.73).
  • 77 clinicians adopted the NAAN App within 6 months.

Conclusions:

  • Multidisciplinary adoption of inpatient penicillin DOC is safe and feasible.
  • Penicillin DOC significantly improved penicillin prescribing and reduced the use of restricted antibiotics.
Abstract

Keywords:
allergyantibiotic allergyantimicrobial stewardshipdelabelingdirect oral challenge

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