Geisinger Antibiotic Allergy Pilot Program: Assess and Address (GAAP) Penicillin Allergy De-labeling in Inpatient Setting by Performing Direct Oral Amoxicillin Challenge in Low-risk Patients

In low-risk patients, as determined by the GAAP questionnaire, the investigator will discuss the option of graded challenge. This will involve initially administering 1/5th (56 mg) of the goal dose of amoxicillin (256 mg) by oral route following the procedure outlined below. The total goal dose to be administered is amoxicillin 256 mg (3.2 ml of 400 mg/5 ml).

Patients will be monitored for 30 minutes after administration of the first amoxicillin dose. If no adverse/allergic symptoms (as listed below) are noted, the rest of the amoxicillin dose will be administered, and the patient will be monitored for an additional 90 minutes.

The amoxicillin challenge will be performed on a monitored bed with telemetry and appropriate nursing coverage. The presence of bedside Benadryl 50 mg, Epinephrine (0.3 mg intramuscular), systemic steroids, and inhalational albuterol should be ensured. Glucagon will be added to the anaphylaxis order set to be used in patients with anaphylaxis who are on the beta-adrenergic blocker if needed throughout the duration of the study. However, no adverse event associated with the interference with anaphylaxis treatment due to the use of beta-adrenergic blocker has been reported in literature on amoxicillin graded challenge. Also, no prior study done on the graded challenge excludes the patients on beta-adrenergic blocker because the patients deemed appropriate for the graded challenge are not likely to develop anaphylaxis. The benefit in de-labeling penicillin allergy in this group far exceeds the risk of the theoretical but unreported adverse event. We will refer to EPIC order set "Anaphylaxis" if any adverse allergic reactions occur and medications are already available for use on each unit/floor to combat allergic reactions as standard of care.

The below steps were taken to design and modify the GAAP questionnaire to optimize the validity for use in this study to identify risk of participating in the graded challenge :

1. Conduct a Literature Review: Our goal is to ensure the questions align with the intended use of the questionnaire, which is to safely stratify the hospitalized patients with history of penicillin or penicillin-derivative allergy to make decision on amoxicillin graded challenge during the same hospitalization. Some of the questions have been used in the reviewed studies in different formats.
2. Develop Items: Each item in the questionnaire is developed to ensure that the users (i.e., the providers who use the questionnaires to interview the patients) and the patients understand them clearly and the provider answers with no or minimal error. We removed any ambiguous and technical terms that may require the assistance of allergy/immunology specialty so that any general provider with basic medical training can understand each item.
3. Conduct Expert Validation: We have had three allergy/immunology specialists establish that individual items are relevant to the construct being measured and that the key items have not been omitted. This systemic review improved the overall quality and representativeness of the scoring system in the questionnaire, which is the unique element of this questionnaire.
4. Conduct Cognitive Interviews: Once the questionnaire was built and reviewed by the experts, we asked several general providers (i.e., house staff, internist, etc.) and patients to assess how prospective participants interpret the items in the questionnaire.
5. Conduct Pilot Testing: A pilot test was done and reported in the protocol that has been submitted for your review previously. The purpose of the pilot test was to 1) identify items that may not be functioning in the intended way, 2) ensure the clarity and easiness of each item for prospective participants to understand, and 3) support the safety in using the questionnaire in deciding on amoxicillin graded challenge.