Single-step direct drug provocation testing is safe for delabelling selected non-low-risk penicillin allergy labels

Background: Penicillin allergy labels are prevalent, and removal of incorrect labels improves patient outcomes and health economics. Labels may be classified as "low-risk" or "non-low-risk," of which the symptoms of the latter chiefly suggest immunoglobulin E-mediated etiology. Traditionally, "non-low-risk" allergy labels are evaluated by penicillin skin testing followed by graded multistep penicillin drug provocation testing (DPT). Objective: To evaluate the safety of assessing "non-low-risk" labels with single-step direct DPT. Methods: We consecutively enrolled inpatients and outpatients of a teaching hospital in Sydney, Australia, with penicillin allergy labels requiring penicillin for first-line treatment. Patients were classified as "low-risk" or "non -low-risk" based on the allergy labels. All patients proceeded directly to amoxicillin DPT, unless there was a history of anaphylaxis within 10 years of assessment to a beta-lactam (except for cefazolin) or Gell and Coombs type 2, type 3, or severe type 4 reaction. This was followed by a course of amoxicillin. Results: A total of 149 patients (41 inpatients, 108 outpatients) were enrolled. No patient was excluded from the study. No patient experienced life-threatening reactions to the protocol. There were 85 patients who reported "non-low-risk" allergy labels. One patient developed generalized pruritus and rash that resolved with standarddose antihistamines, 2 developed delayed benign maculopapular exanthem, and 3 experienced diarrhea during the course of amoxicillin. Conclusion: In our cohort, direct single-step DPT was safe, with only 6 patients with "non-low-risk" allergy experiencing benign reactions. We hope that further studies can be performed into single-step direct DPT to evaluate "non-low-risk" penicillin allergy labels. Trial Registration: ClinicalTrials.gov Identifier: LNR/16/HAWKE/452. (c) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.