PMID- 32176248 OWN - NLM STAT- MEDLINE DCOM- 20210120 LR - 20220727 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 180 IP - 5 DP - 2020 May 1 TI - Development and Validation of a Penicillin Allergy Clinical Decision Rule. PG - 745-752 LID - 10.1001/jamainternmed.2020.0403 [doi] AB - 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 rangeIQR, 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. FAU - Trubiano, Jason A AU - Trubiano JA AD - Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Australia. AD - Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia. AD - Peter MacCallum Cancer Centre, Department of Infectious Diseases and The National Centre for Infections in Cancer, Parkville, Australia. FAU - Vogrin, Sara AU - Vogrin S AD - Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Australia. FAU - Chua, Kyra Y L AU - Chua KYL AD - Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Australia. FAU - Bourke, Jack AU - Bourke J AD - Department of Allergy and Immunology, Fiona Stanley Hospital, Murdoch, Australia. FAU - Yun, James AU - Yun J AD - Faculty of Medicine and Health, University of Sydney, Sydney, Australia. FAU - Douglas, Abby AU - Douglas A AD - Peter MacCallum Cancer Centre, Department of Infectious Diseases and The National Centre for Infections in Cancer, Parkville, Australia. FAU - Stone, Cosby A AU - Stone CA AD - Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tennessee. FAU - Yu, Roger AU - Yu R AD - Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tennessee. FAU - Groenendijk, Lauren AU - Groenendijk L AD - Faculty of Medicine and Health, University of Sydney, Sydney, Australia. FAU - Holmes, Natasha E AU - Holmes NE AD - Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Australia. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tennessee. AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia. LA - eng GR - K12 HS026395/HS/AHRQ HHS/United States GR - P50 GM115305/GM/NIGMS NIH HHS/United States GR - R34 AI136815/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PT - Validation Study PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Anti-Bacterial Agents) RN - 0 (Penicillins) SB - IM CIN - J Urol. 2020 Oct;204(4):869. PMID: 32701374 CIN - MMW Fortschr Med. 2020 Aug;162(14):26. PMID: 32780392 CIN - J Allergy Clin Immunol Pract. 2022 Jul;10(7):1919-1921.e1. PMID: 35398550 MH - Aged MH - Anti-Bacterial Agents/*adverse effects MH - Clinical Decision Rules MH - Drug Hypersensitivity/*etiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Penicillins/*adverse effects MH - Prospective Studies MH - Risk Assessment PMC - PMC7076536 COIS- 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. EDAT- 2020/03/17 06:00 MHDA- 2021/01/21 06:00 PMCR- 2021/03/16 CRDT- 2020/03/17 06:00 PHST- 2020/03/17 06:00 [pubmed] PHST- 2021/01/21 06:00 [medline] PHST- 2020/03/17 06:00 [entrez] PHST- 2021/03/16 00:00 [pmc-release] AID - 2762878 [pii] AID - ioi200012 [pii] AID - 10.1001/jamainternmed.2020.0403 [doi] PST - ppublish SO - JAMA Intern Med. 2020 May 1;180(5):745-752. doi: 10.1001/jamainternmed.2020.0403.