Most Patients with a “Penicillin Allergy Label” Can Safely Take Penicillin

Jennifer Middleton, MD, MPH
Posted on December 18, 2023

It’s that time of year again when strep throat and other bacterial infections circulate in the United States, which means it’s also that time of year to make treatment decisions for patients who have a penicillin allergy listed in their chart. Prescribing other, typically broader spectrum, antibiotics instead of penicillin can contribute to antimicrobial resistance and increased adverse effects. Although 10% of the U.S. population reports a penicillin allergy, data from the Centers for Disease Control and Prevention shows that only about 1% of the U.S. population has a true IgE-mediated penicillin allergy. Identifying those patients whose penicillin allergy has resolved over time, or perhaps never existed to begin with, can reduce the use of broader spectrum antibiotics, reduce health care costs, and improve outcomes for patients who need antibiotic therapy.

Most people who report a penicillin allergy were told they had a reaction as an infant or young child (typically a rash), assumed they had an allergy because a family member did, and/or experienced adverse effects (such as nausea) that are not IgE-mediated. Additionally, approximately 80% of patients with a documented IgE allergy “lose their sensitivity after 10 years.” A good history can remove penicillin allergies from the charts of patients with adverse effects (not allergy) and those patients who assumed they were allergic without personal history of any issue. A clinical prediction rule, PEN-FAST, identifies which remaining adult patients may safely take an observed test dose of oral penicillin (PEN-FAST score less than 3, according to the PALACE trial) and which should be referred to an allergist for skin testing. Another recent trial evaluated adults with a listed penicillin allergy in group visits, risk-assessed them using a different score called PARSS, and then challenged low-risk participants with oral amoxicillin; after 60 minutes of observation, participants without an adverse reaction (108 of 109 in this study who received the oral amoxicillin challenge) had their penicillin allergy removed from their chart. (No trial has yet assessed this rule in pediatric patients, and the American Association of Allergy and Immunology recommends skin testing to verify the veracity of penicillin allergy in this age group.) The author of the trial that identified the PEN-FAST cut-off score recognized that not all patients will be comfortable with a direct oral challenge:

Penicillin allergies have been a source of anxiety for lots of people for several years. I know patients that were told “You’ll die if you ever take penicillin again.” For these individuals, providers can consider skin testing to reassure patients that we are being appropriately cautious before giving them a test dose. However, when we talk to our patients about their low-risk penicillin allergies, 85% of them typically agree to just take a test dose under medical observation.

It’s important for both our patients and the broader public good to delabel patients with inaccurate penicillin allergies. Penicillins are the drug of choice for many infections, are relatively narrow spectrum, are lower cost, and are often better tolerated than alternative antibiotics.

If you have yet to challenge a documented penicillin allergy and/or if you'd like to read more, check out these AFP articles on “Predicting True Penicillin Allergy in Adults,” “Easy Rule Identifies Patients with Low-Risk Penicillin Allergies,” and “Allergy Testing: Common Questions and Answers.” The CDC also has resources on “Evaluation and Diagnosis of Penicillin Allergy for Healthcare Professionals” and a helpful infographic when asking “Is It Really a Penicillin Allergy?” My resolution for the upcoming new year will be to obtain more history and, when appropriate, challenge reported penicillin allergies in my patients.