Inpatient Penicillin Allergy Evaluation—Skin Testing Versus Direct Oral Challenge?

Authors:

• McDanel, Deanna L.
• Mitri, Elise A.
• Li, James T.
• Brockow, Knut

Details:

The Journal of Allergy and Clinical Immunology: In Practice, 2025-12-18

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Penicillin allergy labels are common among patients needing antibiotic treatment. They impact personal treatment outcomes and have public health implications, particularly in the inpatient setting where there is high utilization of antibiotics. Mislabeled allergies often lead to the use of alternative and less effective antibiotics that cause more side effects and contribute to antimicrobial resistance. Penicillin allergy evaluation typically involves 2 main approaches, penicillin skin testing or direct oral challenge. The choice between these strategies is largely driven by risk stratification, availability of resources, health care provider education and training, and patient and provider comfort with testing procedures. Penicillin skin testing is the historical criterion standard diagnostic approach for all-risk phenotypes with an excellent safety record, although it requires specialized training and resources. Direct oral challenge is simpler and is noninferior in low-risk patients, yet it may carry increased risk if patient selection is not rigorous. Both approaches share the common goal of safely “delabeling” penicillin allergies to optimize antibiotic prescribing yet differ in process and have their own limitations. Widespread and routine penicillin allergy evaluation in inpatient care is integral for successful antibiotic stewardship. This article presents the pros and cons for penicillin skin testing versus direct oral challenge for penicillin allergy evaluation in the inpatient setting.