Point-of-Care Guides

Predicting True Penicillin Allergy in Adults


Am Fam Physician. 2021 Jun 15;103(12):760-761.

Author disclosure: No relevant financial affiliations.

Clinical Question

In patients reporting a penicillin allergy, is it possible to determine the likelihood of true allergy without formal testing?

Evidence Summary

Penicillin allergy is the most commonly documented drug allergy in medical records, with a prevalence of approximately 10% of all patients.1 However, in up to 90% of patients with a reported allergy, penicillins are tolerated on allergy testing.2 As a consequence of patients being labeled as having a penicillin allergy, alternative (typically broader-spectrum) antibiotic classes are often used, with potentially poorer efficacy and safety profiles. This leads to increased multidrug-resistant organisms, treatment failure, and health care costs and prolonged hospitalizations.3

A formal drug challenge is the preferred test for investigating immunoglobulin E–mediated penicillin hypersensitivity (type I hypersensitivity)4; skin testing is also a commonly used validated tool.1 A number of studies have been performed to develop clinical prediction rules using features of the allergy history to help determine which patients labeled as having a penicillin allergy can safely be given a beta-lactam antibiotic. Despite the high prevalence of patients labeled as having a penicillin allergy, there is an international shortage of those proficient in conducting formal drug challenges.5

A study in a tertiary referral center in the United Kingdom used multivariable logistic regression to identify patients at low risk of type I beta-lactam allergy.6 This included patients who had no history of anaphylaxis, who had a reaction more than one year before referral, and who could not recall what the index drug was. Only 1.6% of patients with all of these traits had type I hypersensitivity. Another study derived and validated two algorithms in a retrospective cohort of individuals evaluated for beta-lactam allergy.7 Similarly, anaphylaxis, shorter time since the reaction occurred, and reaction onset less than one hour after most recent

Address correspondence to Frank Moriarty, MPharm, PhD, at frankmoriarty@rcsi.ie. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


show all references

1. Sacco KA, Bates A, Brigham TJ, et al. Clinical outcomes following inpatient penicillin allergy testing: a systematic review and meta-analysis. Allergy. 2017;72(9):1288–1296....

2. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259–273.

3. Shenoy ES, Macy E, Rowe T, et al. Evaluation and management of penicillin allergy: a review. JAMA. 2019;321(2):188–199.

4. Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. 2006;354(6):601–609.

5. Trubiano JA, Beekmann SE, Worth LJ, et al. Improving antimicrobial stewardship by antibiotic allergy delabeling: evaluation of knowledge, attitude, and practices throughout the emerging infections network. Open Forum Infect Dis. 2016;3(3):ofw153.

6. Siew LQC, Li PH, Watts TJ, et al. Identifying low-risk beta-lactam allergy patients in a UK tertiary centre. J Allergy Clin Immunol Pract. 2019;7(7):2173–2181.e1.

7. Chiriac AM, Wang Y, Schrijvers R, et al. Designing predictive models for beta-lactam allergy using the drug allergy and hypersensitivity database. J Allergy Clin Immunol Pract. 2018;6(1):139–148.e2.

8. Trubiano JA, Vogrin S, Chua KYL, et al. Development and validation of a penicillin allergy clinical decision rule. JAMA Intern Med. 2020;180(5):745–752.

9. Salkind AR, Cuddy PG, Foxworth JW. The rational clinical examination. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. JAMA. 2001;285(19):2498–2505.

10. Macy E, Ho NJ. Adverse reactions associated with therapeutic antibiotic use after penicillin skin testing. Perm J. 2011;15(2):31–37.

This guide is one in a series that offers evidence-based tools to assist family physicians in improving their decision-making at the point of care.

This series is coordinated by Mark H. Ebell, MD, MS, deputy editor for evidence-based medicine.

A collection of Point-of-Care Guides published in AFP is available at https://www.aafp.org/afp/poc.



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