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Wednesday 13 February 2019
Evaluation and management of penicillin allergy: a review

This week we suggest to read "Evaluation and management of penicillin allergy", an article published on Jama Network on January 15, 2019.


Antibiotics are among the most commonly prescribed medications across health care settings. A substantial portion of antibiotic use is inappropriate, which contributes to antimicrobial resistance and a variety of adverse outcomes. Antibiotic selection is often guided by a patient’s allergy history, with an allergy to penicillin commonly reported. Yet, true IgE-mediated allergies, that cause anaphylaxis, are uncommon. Most patients labeled with penicillin allergy do not undergo any evaluation. The authors summarized the work of different scientific societies, which reviewed articles published between January 1, 2005, and September 30, 2018, about the epidemiology of, clinical consequences of, and methods for evaluating penicillin allergy, providing toolkits to facilitate these evaluations.

Penicillin is commonly associated with hypersensitivity reactions, most likely related to their frequent use and infection-related drug interactions. About 0.5% to 2.0% of penicillin administrations result in a reaction that could be consistent with a hypersensitivity reaction, but that could also be nonallergic.

Most reports of penicillin allergy describe an unknown or cutaneous reaction. Many patients (26%) with a reported penicillin allergy do not have any reaction characteristics documented in the electronic health record (EHR); other commonly documented reactions are rash (38%), hives (18%), angioedema (9%), gastrointestinal upset (6%), anaphylaxis (5%), and itching (5%). For patients, whose allergy history excludes blistering rash, hemolytic anemia, nephritis, hepatitis, fever, and joint pain suggestive of organ involvement or severe cutaneous adverse reactions (SCAR) in response to penicillin, an allergy evaluation of some form is indicated. More than 95% of patients who do not have a history of serious penicillin allergy reactions are penicillin tolerant.

The consequences of being labeled as having a penicillin allergy include the use of alternative antibiotics, that cause more treatment failures and adverse effects than β-lactams (e.g., increased risk of surgical site infections when used in perioperative prophylaxis), contribute to antimicrobial resistance development (e.g., C. difficile infection, methicillin-resistant S. aureus, and vancomycin resistant enterococcus), and increase pharmacy costs.

A comprehensive history is essential for proper evaluation of a patient with a reported penicillin allergy. Although there are many types of rashes that result from infectious, environmental, and/or autoimmune triggers, the authors proposed 3 general categories: IgE-mediated cutaneous reactions (e.g., urticaria), benign T-lymphocyte–mediated cutaneous reactions, and SCAR. After the allergy history is determined to be inconsistent with SCAR, hemolytic anemia, an organ-specific reaction, drug fever, or serum sickness, patients can be stratified into low, moderate, and high risk. The baseline risk for any reaction to β-lactam antibiotics is approximately 2.0%.

  • Patients with low-risk history (most of the patients): prescribe amoxicillin or perform a direct amoxicillin challenge (250 mg or 500 mg, divided into 2 or 3 separate administrations, with 1 hour of observation demonstrates penicillin tolerance). Demonstration of amoxicillin tolerance enables future use of all penicillin antibiotics.
  • Patients with moderate-risk history (pruritic rashes or reactions, but not anaphylactic reactions): penicillin skin testing should be done; if positive, patients are allergic and should not be challenged; if negative, they carry a predictive value of about 100%, when combined with oral amoxicillin challenge.
  • Patients with high-risk history (anaphylaxis, positive penicillin skin testing results, recurrent penicillin reactions, and hypersensitivities to multiple β-lactam antibiotics) should be referred to allergy/immunology specialist or undergo desensitization.

Algorithms exist to help prescribe β-lactam agents to patients with a reported penicillin allergy. However, evaluating the penicillin allergy directly is the simplest approach.

Penicillin allergy evaluation can be safely performed before the need for antibiotic use.

Most reactions that occur, as a result of testing, are either subjective symptoms or minor cutaneous reactions. Rarely, patients may develop anaphylaxis. If an amoxicillin challenge is tolerated, the medical record notation that a patient is allergic to penicillin should be deleted (updating the EHR). Amoxicillin challenges virtually exclude IgE-mediated allergies, but patients may experience other benign skin rashes, as the general population. The authors concluded highlighting that many patients report an allergy to penicillin, but few have clinically significant reactions, and that evaluation of penicillin allergy, before deciding not to use penicillin or other β-lactam antibiotics, is an important tool for antimicrobial stewardship.

AUTHORS: Erica S. Shenoy, Eric Macy, Theresa Rowe

The article is available here: