Penicillin Allergy Delabeling After a One-Dose Versus Two-Dose Graded Direct Oral Challenge

Anywhere from 5-15% of patients have a reported penicillin allergy listed in their medical record. However, most patients with this listed allergy had reactions with characteristics that would qualify their penicillin allergy as low-risk of having a subsequent serious reaction (when considering initial reaction symptoms, time since initial reaction and if treatment was required). Of patients with penicillin allergy listed, it has been demonstrated that >90% can tolerate penicillin after further evaluation, indicating a significant number of patients with an unnecessary penicillin allergy label.

Penicillin allergy delabeling is a practice commonly performed by allergists to test patients for safe removal of penicillin allergy from their medical records. The protocol of penicillin allergy delabeling has historically consisted of a skin test, followed by a two-step graded direct oral challenge, in which patients are given a smaller, then larger, oral dose of amoxicillin, a penicillin-containing medication. The patient is monitored closely throughout the process for reaction to penicillin and, if necessary, treatment is given for management of reaction symptoms. This method, though functional, takes time and resources to delabel patients.

As our understanding of penicillin drug allergy evolves, it may be possible to reduce the number of steps (and therefore resources) necessary to safely remove penicillin allergy labels. New data suggests that skin testing may not be a necessary step in penicillin allergy delabeling in a subset of low-risk patients. It has also been demonstrated in several studies that a single-dose direct oral challenge (rather than a two-step graded dose) is safe. A recent pilot study also showed that penicillin allergy delabeling can be safely performed in a primary care setting without the direct supervision of an allergist.

Per the authors' literature review, no prospective studies have directly compared the safety and efficacy of a single-dose versus a two-dose graded direct oral challenge. We propose a non-inferiority study in which patients classified as having a low-risk penicillin allergy are randomized into two groups and then receive either a single-dose or the traditional two-dose graded direct oral challenge to be able to evaluate these two treatment protocols in a side-by-side fashion. The results will contribute to our understanding of if a single-dose direct oral challenge can be safely used in place of the traditional two-dose graded direct oral challenge, thus reducing barriers for implementation in a primary care setting.

Patients with penicillin allergy that express interest through publicly posted recruitment materials will be screened to determine if they meet criteria for a "low-risk" allergy through the PEN-FAST screening tool, a recently developed, externally validated penicillin allergy risk assessment calculator. Those that meet the low-risk criteria and other eligibility criteria will be scheduled for an outpatient delabeling appointment. Participants will be randomly assigned in a double-blinded manner to receive either a two-dose graded direct oral challenge (DOC) with amoxicillin or a one-dose DOC placebo, followed by amoxicillin. Each group will receive the same cumulative dose of amoxicillin by the end of the challenge. Participants assigned to the two-dose graded DOC will be administered 62.5mg amoxicillin (25% of the full dose), followed by 187.5mg amoxicillin. Patients assigned to the one-dose DOC will be administered a placebo (Syrpalta or similar, a syrup used in drug compounding), followed by 250mg amoxicillin.