The challenge of de-labeling penicillin allergy

Allergy. 2020 Feb;75(2):273-288. doi: 10.1111/all.13848. Epub 2019 May 26.


Background: Even though 8%-25% of most populations studied globally are labeled as penicillin allergic, most diagnoses of penicillin allergy are made in childhood and relate to events that are either not allergic in nature, are low risk for immediate hypersensitivity, or are a potential true allergy that has waned over time. Penicillin allergy labels directly impact antimicrobial stewardship by leading to use of less effective and broader spectrum antimicrobials and are associated with antimicrobial resistance. They may also delay appropriate antimicrobial therapy and lead to increased risk of specific adverse healthcare outcomes. Operationalizing penicillin allergy de-labeling into a new arm of antimicrobial stewardship programs (ASPs) has become an increasing global focus.

Methods: We performed an evidence-based narrative review of the literature of penicillin allergy label carriage, the adverse effects of penicillin allergy labels, and current approaches and barriers to penicillin allergy de-labeling. Over the period 1928-2018 in Pubmed and Medline, search terms used included "penicillin allergy" or "penicillin hypersensitivity" alone or in combination with "adverse events," "testing," "evaluation," "effects," "label," "de-labeling," "prick or epicutaneous," and "intradermal" skin testing, "oral challenge or provocation," "cross-reactivity," and "antimicrobial stewardship".

Results: Penicillin allergy labels are highly prevalent, largely inaccurate and their carriage may lead to unnecessary treatment and inferior outcomes with alternative agents as well as adverse public health outcomes such as antibiotic resistance.

Conclusions: Operationalizing penicillin allergy de-labeling as an aspect of ASP has become an increasing global focus. There is a need for validated approaches that optimally combine the use of history and ingestion challenge with or without proceeding formal skin testing to tackle penicillin allergy efficiently within complex healthcare systems. At the same time, there is great promise for penicillin allergy evaluation and de-labeling as an individual and public health strategy to reduce adverse healthcare outcomes, improve antimicrobial stewardship, and decrease healthcare costs.

Keywords: allergy; de-labeling; label; penicillin; testing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / chemistry
  • Antimicrobial Stewardship / methods
  • Cephalosporins / adverse effects
  • Cephalosporins / chemistry
  • Child
  • Child, Preschool
  • Cross Reactions
  • Desensitization, Immunologic
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / immunology
  • Humans
  • Intradermal Tests
  • Penicillins / adverse effects*
  • Penicillins / chemistry


  • Anti-Bacterial Agents
  • Cephalosporins
  • Penicillins