Allergy to penicillin is commonly reported, but immunoglobulin E (IgE)-mediated allergies and anaphylaxis are rare, and most patients are able to tolerate penicillin and other beta-lactam antibiotics. But determining whether a true allergy exists is imperative-antibiotics are among the most commonly prescribed medications, and their misuse contributes to antimicrobial resistance and adverse outcomes. Amid widespread recommendations to implement policies and practices to reduce inappropriate antibiotic use, experts from the American Academy of Allergy, Asthma, and Immunology; the Infectious Diseases Society of America; and the Society for Healthcare Epidemiology of America reviewed the literature, summarizing the epidemiology and clinical consequences of penicillin allergy and detailing methods for evaluating allergic reactions.

IgE-mediated penicillin allergies are becoming less common, possibly because of the less frequent use of parenteral penicillin. This type of allergy wanes over time, with 80% of patients becoming tolerant after a decade. Most reports of penicillin allergy describe an unknown or cutaneous reaction. For patients with penicillin allergy but no history of a serious penicillin allergic reaction, such as a blistering rash or nephritis, further evaluation is indicated. More than 95% of these patients can tolerate penicillin.

Patients labeled as having an allergy to penicillin may be given an alternative antibiotic that is less effective, has more adverse effects, and contributes to antimicrobial resistance. Reevaluating a patient's report of penicillin allergy can lead to multiple benefits: less frequent use of costly broad-spectrum antibiotics, a reduction in antimicrobial resistance, fewer adverse effects and drug reactions, and a reduced risk of developing Clostridium difficile and other infections.

The authors provide toolkits to help nonspecialists with risk stratification of patients with reported penicillin allergy. The characteristics of patients at low risk, moderate risk, and high risk are described. Tips for penicillin allergy evaluations in each of these groups are included, as are tips for testing during routine care, including among special populations (patients who are hospitalized, pediatric patients, pregnant women, long-term care patients, and cancer patients, for example). The authors also discuss how to manage drug challenge reactions.

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