PROPELing risk-stratified penicillin allergy delabeling into sustainable inpatient programs
Published online July 15, 2025
It has become increasingly well known that not all of the events that are currently reported by patients as a penicillin allergy label are equally risky to be a true penicillin allergy when tested. Validated risk stratification schemes such as PEN-FAST or the Vanderbilt risk assessment are known to identify up to 70% of patients with penicillin allergy labels as “low-risk” for an ongoing allergy. Such patients can be safely tested by taking a direct challenge with amoxicillin under medical observation, with a high negative predictive value for excluding patients who will react (an observed rate of around 1 in 200 experiencing a rash). In the head-to-head clinical trial known as PALACE, it was shown that skin testing prior to challenge did not add additional value in the evaluation of patients who stratify as “low-risk,” compared to a direct challenge.
The “Pragmatic Removal of Penicillin Allergy Electronic Health Record Labels,” or “PROPEL” trial, by Stone et al., is now published in The Journal of Allergy and Clinical Immunology: In Practice. This manuscript focuses on the practical question of “How can we implement this new knowledge into a working, permanent hospital risk-stratified delabeling program, using minimal resources?” The AHRQ-funded, AAAAI Foundation-supported PROPEL trial thus built upon the lessons learned from a long-term ICU pilot study at Vanderbilt University Medical Center, and consisted of two components: 1. a one-time educational opportunity for staff and 2. an electronic health record decision-support resource for pharmacists that was deployed at randomized 1-month intervals to 12 participating inpatient units, in a stepped wedge trial design. The study’s goals were pragmatic: to determine whether this “minimal” amount of intervention would increase the rate of penicillin allergy risk-assessments and delabeling by pharmacists who were asked to “do it as often as you can” rather than by dedicated champions who considered it a key component of their workflow.
Among the 2,052 patients admitted to a participating unit with an existing penicillin allergy label, those who received care on a unit after the intervention went live were significantly more likely to have their penicillin allergies tested and removed during their hospitalization. The intervention more than doubled the odds of a patient having a penicillin allergy label removed and increased the odds of oral challenge testing to determine if a penicillin allergy exists. While the absolute numbers of patients delabeled remained low, the authors were able to demonstrate an increase in delabeling that added on to the efforts of their “champion drive” ICU delabeling program, even during the peak of the COVID pandemic. Once implemented, their intervention has now become a permanent, sustainable inpatient program and has continued delabeling patients on a daily basis for the last five years. The PROPEL trial in combination with their ICU pilot studies, demonstrates a pragmatic roadmap to sustainable risk-stratified inpatient penicillin delabeling programs using no additional resources. PROPEL also provides high quality RCT evidence that such programs can achieve their intended delabeling goals even in the middle of a pandemic. The authors speculate that additional investments in proactive inpatient penicillin allergy delabeling programs that feature dedicated champions are likely to meet with even greater success.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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