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Development and Validation of a Penicillin Allergy Clinical Decision Rule

Educational Objective
Review research on evaluating penicillin allergy risk and severity.
1 Credit CME
Key Points

Question  Can a clinical decision rule risk stratify penicillin allergies and identify low-risk phenotypes amenable to point-of-care delabeling?

Findings  In this diagnostic study of 622 patients, a penicillin allergy decision rule (PEN-FAST) was derived from a prospective cohort of penicillin allergy–tested patients in 2 primary Australian sites and was subjected to internal and external validation in 3 local and international cohorts. PEN-FAST was found to be a practical tool with a high negative predictive value of 96.3% that uses penicillin allergy history to identify low-risk allergies.

Meaning  PEN-FAST may aid the risk stratification of patients with penicillin allergy to facilitate implementation of delabeling strategies and safe β-lactam prescribing.

Abstract

Importance  Penicillin allergy is a significant public health issue for patients, antimicrobial stewardship programs, and health services. Validated clinical decision rules are urgently needed to identify low-risk penicillin allergies that potentially do not require penicillin skin testing by a specialist.

Objective  To develop and validate a penicillin allergy clinical decision rule that enables point-of-care risk assessment of patient-reported penicillin allergies.

Design, Setting, and Participants  In this diagnostic study, a multicenter prospective antibiotic allergy–tested cohort of 622 patients from 2 tertiary care sites in Melbourne, Australia (Austin Health and Peter MacCallum Cancer Centre) was used for derivation and internal validation of a penicillin allergy decision rule. Backward stepwise logistic regression was used to derive the model, including clinical variables predictive of a positive penicillin allergy test result. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in retrospective penicillin allergy–tested cohorts consisting of 945 patients from Sydney and Perth, Australia, and Nashville, Tennessee. Patients who reported a penicillin allergy underwent penicillin allergy testing using skin prick, intradermal, or patch testing and/or oral challenge (direct or after skin testing). Data were collected from June 26, 2008, to June 3, 2019, and analyzed from January 9 to 12, 2019.

Main Outcomes and Measures  The primary outcome for the model was any positive result of penicillin allergy testing performed during outpatient or inpatient assessment.

Results  From an internal derivation and validation cohort of 622 patients (367 female [59.0%]; median age, 60 [interquartile range{IQR}, 48-71] years) and an external validation cohort of 945 patients (662 female [70.1%]; median age, 55 [IQR, 38-68] years), the 4 features associated with a positive penicillin allergy test result on multivariable analysis were summarized in the mnemonic PEN-FAST: penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR), and treatment required for allergy episode. The major criteria included an allergy event occurring 5 or fewer years ago (2 points) and anaphylaxis/angioedema or SCAR (2 points); the minor criterion (1 point), treatment required for an allergy episode. Internal validation showed minimal mean optimism of 0.003 with internally validated area under the curve of 0.805. A cutoff of less than 3 points for PEN-FAST was chosen to classify a low risk of penicillin allergy, for which only 17 of 460 patients (3.7%) had positive results of allergy testing, with a negative predictive value of 96.3% (95% CI, 94.1%-97.8%). External validation resulted in similar findings.

Conclusions and Relevance  In this study, PEN-FAST was found to be a simple rule that accurately identified low-risk penicillin allergies that do not require formal allergy testing. The results suggest that a PEN-FAST score of less than 3, associated with a high negative predictive value, could be used by clinicians and antimicrobial stewardship programs to identify low-risk penicillin allergies at the point of care.

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Article Information

Accepted for Publication: February 1, 2020.

Corresponding Author: Jason A. Trubiano, MBBS, PhD, Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, 145 Studley Road, Heidelberg, Victoria, Australia 3084 (jason.trubiano@austin.org.au).

Published Online: March 16, 2020. doi:10.1001/jamainternmed.2020.0403

Author Contributions: Drs Trubiano and Vogrin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Trubiano, Stone, Phillips.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Trubiano, Stone, Groenendijk, Phillips.

Critical revision of the manuscript for important intellectual content: Trubiano, Vogrin, Chua, Bourke, Yun, Douglas, Stone, Yu, Holmes, Phillips.

Statistical analysis: Trubiano, Vogrin, Stone.

Obtained funding: Trubiano.

Administrative, technical, or material support: Trubiano, Chua, Yun, Douglas, Stone, Groenendijk, Phillips.

Supervision: Trubiano, Stone, Phillips.

Conflict of Interest Disclosures: Dr Stone reported receiving grant 1K12HS026395-01 from the Agency for Healthcare Research and Quality (AHRQ) during the conduct of the study. Dr Phillips reported receiving grants from the National Institutes of Health (NIH) and National Health and Medical Research Council (NHMRC) and personal fees from UpToDate, Inc and BioCryst Pharmaceuticals, Inc outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by a grant from the Austin Medical Research Foundation (AMRF); postgraduate scholarship GNT 1139902 from the NHMRC (Dr Trubiano); a postgraduate scholarship from the National Centre for Infections in Cancer (Dr Trubiano); grants 1P50GM115305-01, R21AI139021, R34AI136815, and 1R01HG01086301 from the NIH (Dr Phillips); the NHMRC (Dr Phillips); and grant 1K12HS026395-01 from the AHRQ (Dr Stone).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The departments of Infectious Diseases at Austin Health and Peter MacCallum Cancer Centre assisted with the antibiotic allergy testing services, for which they were not compensated.

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