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Figure.  Association of Documented Penicillin Allergies With Inpatient Antibiotic Use Among US Inpatients
Association of Documented Penicillin Allergies With Inpatient Antibiotic Use Among US Inpatients

Adjusted odds ratios (aORs) are adjusted for age, sex, race/ethnicity, length of hospitalization, number of staffed beds, hospital geographic location, diabetes, cephalosporin allergy, inpatient location within the hospital, and number of specific infections treated.

Table.  Multivariable Assessment of the Association of Documented Penicillin Allergies With Inpatient Antibiotic Use
Multivariable Assessment of the Association of Documented Penicillin Allergies With Inpatient Antibiotic Use
1.
Shenoy  ES, Macy  E, Rowe  T, Blumenthal  KG.  Evaluation and management of penicillin allergy: a review.   JAMA. 2019;321(2):188-199. doi:10.1001/jama.2018.19283 PubMedGoogle ScholarCrossref
2.
MacFadden  DR, LaDelfa  A, Leen  J,  et al.  Impact of reported β-lactam allergy on inpatient outcomes: a multicenter prospective cohort study.   Clin Infect Dis. 2016;63(7):904-910. doi:10.1093/cid/ciw462 PubMedGoogle ScholarCrossref
3.
Bratzler  DW, Dellinger  EP, Olsen  KM,  et al; American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America.  Clinical practice guidelines for antimicrobial prophylaxis in surgery.   Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568 PubMedGoogle ScholarCrossref
4.
Trubiano  JA, Vogrin  S, Chua  KYL,  et al.  Development and validation of a penicillin allergy clinical decision rule.   JAMA Intern Med. 2020;180(5):1-9. doi:10.1001/jamainternmed.2020.0403 PubMedGoogle Scholar
5.
Barlam  TF, Cosgrove  SE, Abbo  LM,  et al.  Executive summary: implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.   Clin Infect Dis. 2016;62(10):1197-1202. doi:10.1093/cid/ciw217 PubMedGoogle ScholarCrossref
6.
Mancini  CM, Fu  X, Zhang  Y,  et al.  Penicillin allergy evaluation access: a national survey.   Clin Infect Dis. Published online May 18, 2020. doi:10.1093/cid/ciaa567Google Scholar
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    Research Letter
    June 29, 2020

    Association Between Penicillin Allergy Documentation and Antibiotic Use

    Author Affiliations
    • 1Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston
    • 2The Mongan Institute, Massachusetts General Hospital, Boston
    • 3Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • 4Vizient Inc, Irving, Texas
    • 5Department of Pharmacy, University of Wisconsin Health, Madison
    • 6Division of Allergy, Immunology, and Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
    • 7Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois
    • 8Division of Infectious Diseases, Department of Pathology and Internal Medicine, The University of Texas Southwestern Medical Center, Dallas
    • 9Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston
    JAMA Intern Med. 2020;180(8):1120-1122. doi:10.1001/jamainternmed.2020.2227

    Quiz Ref IDApproximately half of hospitalized patients receive antibiotics, and more than 10% of these patients have a penicillin allergy documented in the medical record.1Quiz Ref ID Hospitalized patients with ongoing infections who report an allergy to penicillin have an increased risk of adverse drug events, including Clostridioides difficile infection, when not treated with a β-lactam antibiotic.2 Allergy assessment with or without diagnostic testing disproves more than 90% of documented penicillin allergies.1

    The inpatient prevalence and effects of documented penicillin allergies has been exclusively investigated in single hospitals or health care systems. We used a large cross-sectional database of inpatients receiving antibiotics to assess the prevalence and association of documented penicillin allergy with inpatient antibiotic use in the US.

    Methods

    Quiz Ref IDThis cohort study used cross-sectional inpatient data collected through Acute Care Hospital Groups within Vizient Inc, Irving, Texas, from September 2018, through January 2019 (eMethods in the Supplement). Data analysis was performed from January 2019, through January 2020. The study was reviewed by the Partners Human Research Committee, Boston, Massachusetts, and was determined to be exempt because it was categorized as nonhuman research.

    The exposure was an allergy to any penicillin antibiotic documented in the medical record. The outcomes were antibiotic use overall and for specified indications, considering individual antibiotic classes and 2 antibiotic groupings: (1) β-lactam alternative antibiotics and (2) narrow-spectrum β-lactam antibiotics.

    We examined the association of documented penicillin allergy with antibiotic use overall and for specified indications, such as pneumonia, skin and soft-tissue infection, urinary tract infection, and prophylaxis for surgical procedures. We used generalized estimating equations models to account for clustering by hospital with logit link in SAS, version 9.4 (SAS Institute Inc). We report adjusted odds ratios (aORs) with 95% CIs.

    Results

    Of 10 992 inpatients (5567 [51%] male; mean [SD] age, 57.0 [21.5] years) receiving antibiotics at 106 hospitals, 1741 patients (16%) had a penicillin allergy documented in the medical record. Most penicillin reactions (946 of 2112 [45%]) were cutaneous. Patient characteristics by penicillin allergy status were similar.

    Compared with patients without a documented penicillin allergy, patients with a documented penicillin allergy had higher β-lactam alternative antibiotic use (1114 of 1741 [64%] vs 4438 of 9251 [48%]) and lower narrow-spectrum β-lactam antibiotic use (227 of 1741 [13%] vs 2811 of 9251 [30%]).

    In the fully adjusted model (Table), patients with a documented penicillin allergy had increased odds of β-lactam alternative antibiotic use (aOR, 1.94; 95% CI, 1.74-2.17), with especially high odds of clindamycin use (aOR, 5.34; 95% CI, 3.99-7.13). Patients with a documented penicillin allergy had lower odds of narrow-spectrum β-lactam antibiotic use (aOR, 0.35; 95% CI, 0.31-0.40).

    The association between a documented penicillin allergy and β-lactam alternative antibiotic use was stronger among patients receiving antibiotics for urinary tract infection (aOR, 2.07; 95% CI, 1.51-2.85) and as prophylaxis for surgical procedures (aOR, 7.31; 95% CI, 5.01-10.69]) (Figure, A). The association between a documented penicillin allergy and narrow-spectrum β-lactam antibiotic use was stronger among patients receiving antibiotics for pneumonia (aOR, 0.31; 95% CI, 0.19-0.50), urinary tract infection (aOR, 0.26; 95% CI, 0.13-0.54), and as prophylaxis for surgical procedures (aOR, 0.11; 95% CI, 0.07-0.15]) (Figure, B).

    Discussion

    Quiz Ref IDIn this cross-sectional study of 10 992 inpatients receiving antibiotics from 106 US hospitals, 16% of patients with a documented penicillin allergy had almost 2-fold higher odds of receiving a β-lactam alternative antibiotic. We reported the largest increased odds of a specific β-lactam alternative for clindamycin, an antibiotic associated with C difficile infection risk, for which use was more than 5-fold more likely. We identified more than 7-fold increased odds of alternative antibiotic use for inpatients with a documented penicillin allergy receiving antibiotics as prophylaxis for a surgical procedure, a narrow-spectrum β-lactam antibiotic indication for reducing infection risk at the surgical site.1,3 Patients with a penicillin allergy documented in their medical record also had more than 18-fold increased odds of aztreonam use.

    When considering that a small number of the inpatients reporting penicillin allergy would have been truly allergic to penicillin, at least 90% of these antibiotic substitutions were likely unnecessary.1,4 Although penicillin allergy evaluations are recommended as part of inpatient antibiotic stewardship,5 most hospitals do not have access to penicillin allergy assessment.6 However, allergy history alone is associated with a high negative predictive value (96.5%; 95% CI, 94.1%-97.8%) for excluding true penicillin allergy.4

    Quiz Ref IDAlthough our study data came from a large sample of hospitals, these data may not be nationally representative. Cross-sectional data did not permit determination of cumulative antibiotic use metrics.

    The 16% of inpatients with a penicillin allergy documented on their medical record were treated more commonly with alternatives that may be inferior and/or associated with more adverse drug events. Hospitals may target patients prescribed clindamycin or patients with planned surgical procedures for inpatient penicillin allergy interventions.

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    Article Information

    Accepted for Publication: April 27, 2020.

    Corresponding Author: Kimberly G. Blumenthal, MD, MSc, Division of Rheumatology, Allergy and Immunology, The Mongan Institute, Massachusetts General Hospital, 100 Cambridge St, 16th Floor, Boston, MA 02114 (kblumenthal@mgh.harvard.edu).

    Published Online: June 29, 2020. doi:10.1001/jamainternmed.2020.2227

    Author Contributions: Dr Blumenthal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: All authors.

    Acquisition, analysis, or interpretation of data: Blumenthal, Kuper, Schulz, Postelnick, Lee, Walensky.

    Drafting of the manuscript: Blumenthal, Lee.

    Critical revision of the manuscript for important intellectual content: Blumenthal, Kuper, Schulz, Bhowmick, Postelnick, Walensky.

    Statistical analysis: Blumenthal, Lee.

    Obtained funding: Blumenthal.

    Administrative, technical, or material support: Blumenthal, Kuper, Schulz, Walensky.

    Supervision: Schulz, Bhowmick, Walensky.

    Conflict of Interest Disclosures: Dr Blumenthal reported intellectual property for a clinical decision support tool used institutionally for β-lactam allergy assessment at Partners HealthCare System, which is licensed to Persistent Systems. Dr Kuper reported being an employee of Vizient Inc at the time of the study. Dr Lee reported receiving grants from Lynntech outside the submitted work. No other disclosures were reported.

    Funding/Support: Dr Blumenthal was supported by a career development grant (K01AI125631) from the National Institutes of Health; the American Academy of Allergy, Asthma, and Immunology Foundation; and the Massachusetts General Hospital Claflin Distinguished Scholar Award. Dr Walensky was supported by the Steven and Deborah Gorlin Massachusetts General Hospital Research Scholars Award.

    Role of the Funder/Sponsor: The funding organization 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.

    Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health; the American Academy of Allergy, Asthma, and Immunology Foundation; or Massachusetts General Hospital.

    Additional Contributions: Christian M. Mancini, BS, Xioqing Fu, MS, and Yuqing Zhang, DSc (Massachusetts General Hospital, Boston), provided data analytic support. Vizient Inc, Irving, Texas, facilitated this study through their hospital network, including the assistance of Arati Kurani, PharmD, Jade Vitug, PharmD, Larry Huang, PharmD, Alyzeh Haider, MHA, and Sam Hohmann, PhD. Christie Bertram, PharmD (Northwestern Memorial Hospital, Chicago, Illinois), provided administrative study support to the hospitals during data acquisition. None of these individuals was compensated for their assistance.

    References
    1.
    Shenoy  ES, Macy  E, Rowe  T, Blumenthal  KG.  Evaluation and management of penicillin allergy: a review.   JAMA. 2019;321(2):188-199. doi:10.1001/jama.2018.19283 PubMedGoogle ScholarCrossref
    2.
    MacFadden  DR, LaDelfa  A, Leen  J,  et al.  Impact of reported β-lactam allergy on inpatient outcomes: a multicenter prospective cohort study.   Clin Infect Dis. 2016;63(7):904-910. doi:10.1093/cid/ciw462 PubMedGoogle ScholarCrossref
    3.
    Bratzler  DW, Dellinger  EP, Olsen  KM,  et al; American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America.  Clinical practice guidelines for antimicrobial prophylaxis in surgery.   Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568 PubMedGoogle ScholarCrossref
    4.
    Trubiano  JA, Vogrin  S, Chua  KYL,  et al.  Development and validation of a penicillin allergy clinical decision rule.   JAMA Intern Med. 2020;180(5):1-9. doi:10.1001/jamainternmed.2020.0403 PubMedGoogle Scholar
    5.
    Barlam  TF, Cosgrove  SE, Abbo  LM,  et al.  Executive summary: implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.   Clin Infect Dis. 2016;62(10):1197-1202. doi:10.1093/cid/ciw217 PubMedGoogle ScholarCrossref
    6.
    Mancini  CM, Fu  X, Zhang  Y,  et al.  Penicillin allergy evaluation access: a national survey.   Clin Infect Dis. Published online May 18, 2020. doi:10.1093/cid/ciaa567Google Scholar
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