Evaluating Penicillin Allergies Without Skin Testing

  • Taylor A. Banks
  • Mark Tucker
  • Eric MacyEmail author
Anaphylaxis and Drug Allergy (DA Khan and M Castells, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Anaphylaxis and Drug Allergy


Purpose of Review

An unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results.

Recent Findings

Encouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative.


Direct oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.


Adverse drug reaction Antibiotic stewardship program Amoxicillin Delabeling Oral challenge Drug allergy Penicillin Hypersensitivity Skin testing 



American Board of Internal Medicine


Antibiotic stewardship program


Clostridiodes difficile


Emergency Department


US Food and Drug Administration


Kaiser Permanente Southern California


Methicillin-sensitive Staphylococcus aureus


Oral challenge


Serious cutaneous adverse reaction


Skin testing


Vancomycin-resistant Enterococcus


Compliance with Ethical Standards

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

EM is a partner in the Southern California Permanente Medical Group. EM has received research support from the Southern California Permanente Medical Group, grants from ALK Abello, Inc. to study adverse drug reactions, and has served on clinical trial safety and monitoring committees for BioMarin, Ultragenyx, and Audentes.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Allergy/ImmunologyNaval Medical Center PortsmouthPortsmouthUSA
  2. 2.Department of Allergy and ImmunologyNaval Branch Health ClinicSan DiegoUSA
  3. 3.Department of Allergy, Southern California Permanente Medical GroupKaiser PermanenteSan DiegoUSA

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