Multicenter Australian Study to Determine Criteria for Low- and High-Risk Penicillin Testing in Outpatients

Background: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain. Objective: To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing. Methods: In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition. Results: A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9). Conclusions: History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.