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Association Between Penicillin Allergy Documentation and Antibiotic Letters that legalization of recreational marijuana is associated with in- Association Between Penicillin Allergy creased traffic fatality rates. Applying these results to national driv- Documentation and Antibiotic Use ing statistics, nationwide legalization would be associated with Approximately half of hospitalized patients receive antibiot- 6800 (95% CI, 4200-9700) excess roadway deaths each year. De- ics, and more than 10% of these patients have a penicillin spite certain methodological differences, we found an increase allergy documented in the medical record.1 Hospitalized similar to that reported by Aydelotte et al.4 They reported an in- patients with ongoing crease of 1.8 fatal crashes (equivalent to 2.0 fatalities) per BVMT. infections who report an We concur with their opinion that changes may not be detected Supplemental content allergy to penicillin have an immediately after legalization but only after a longer time period increased risk of adverse or after commercial sales begin. CME Quiz at drug events, including Clos- We chose a control group consisting of all states with nei- jamacmelookup.com tridioides difficile infection, ther legal recreational nor medical marijuana to isolate the ef- when not treated with a fects of marijuana. We did not require that control states have β-lactam antibiotic.2 Allergy assessment with or without baseline attributes similar to the experimental states because diagnostic testing disproves more than 90% of documented the difference-in-difference technique removes biases in com- penicillin allergies.1 parisons between experimental and control groups that re- sult from permanent differences between those groups. Our Table. Multivariable Assessment of the Association of Documented conclusions, nonetheless, are limited by adjusting for only 3 Penicillin Allergies With Inpatient Antibiotic Use state-specific factors that may have changed during the study a period. It is possible that another confounder, rather than mari- Odds ratio (95% CI) juana legalization and commercialization, caused the ob- Partially adjusted Fully adjusted Antibiotic modelb modelc served increase in roadway deaths. β-lactam alternativesd 2.04 (1.82-2.27) 1.94 (1.74-2.17) Vancomycin 1.21 (1.07-1.36) 1.14 (1.01,1.29) Russell S. Kamer, MD Fluoroquinolones 1.93 (1.64-2.26) 1.91 (1.61-2.25) Stephen Warshafsky, MD Gordon C. Kamer Macrolides 0.94 (0.78-1.12) 0.94 (0.78-1.12) Sulfonamides 1.14 (0.90-1.45) 1.16 (0.91-1.48) Tetracyclines 1.41 (1.07-1.85) 1.37 (1.03-1.83) Author Affiliations: Department of Medicine, New York Medical College, Valhalla, New York (R. S. Kamer, Warshafsky); Harvard College, Harvard Clindamycin 5.78 (4.39-7.61) 5.34 (3.99-7.13) University, Cambridge, Massachusetts (G. C. Kamer). Aminoglycosides 1.74 (1.34-2.25) 1.53 (1.16-2.02) Corresponding Author: Russell S. Kamer, MD, Department of Medicine, New Linezolid 2.30 (1.45-3.63) 2.18 (1.37-3.48) York Medical College, 15 N Broadway, White Plains, NY 10601 (drkamer@ e drkamer.com). Narrow-spectrum β-lactams 0.33 (0.29-0.38) 0.35 (0.31-0.40) f g g Accepted for Publication: April 13, 2020. Penicillins 0.17 (0.12-0.25) 0.17 (0.12-0.25) Published Online: June 22, 2020. doi:10.1001/jamainternmed.2020.1769 Cephalosporins Author Contributions: Dr R Kamer had full access to all of the data in the study First generation 0.44 (0.37-0.52) 0.47 (0.40-0.55) and takes responsibility for the integrity of the data and the accuracy of the data Second generation 1.30 (0.79-2.12) 1.34 (0.82-2.18) analysis. Concept and design: R. Kamer, Warshafsky. Other β-lactams Acquisition, analysis, or interpretation of data: All authors. Cephalosporins Drafting of the manuscript: All authors. Third generation 0.87 (0.75-1.02) 0.92 (0.78-1.08) Critical revision of the manuscript for important intellectual content: R. Kamer, Warshafsky. Fourth generation 1.44 (1.20-1.72) 1.47 (1.23-1.76) Statistical analysis: All authors. Carbapenems 1.83 (1.48-2.26) 1.72 (1.38-2.14) Supervision: Warshafsky, G. Kamer. Aztreonam or 22.49 (14.39-35.15) 18.44 (11.13-30.55) Conflict of Interest Disclosures: None reported. monobactams 1. Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem. 2013; a Documented penicillin allergy compared with no documented penicillin 59(3):478-492. doi:10.1373/clinchem.2012.194381 allergy. 2. Aydelotte JD, Brown LH, Luftman KM, et al. Crash fatality rates after b Adjusted for age, sex, race/ethnicity, length of hospitalization, inpatient recreational marijuana legalization in Washington and Colorado. Am J Public Health. location within the hospital, and number of infections. 2017;107(8):1329-1331. doi:10.2105/AJPH.2017.303848 c Adjusted for age, sex, race/ethnicity, length of hospitalization, number of 3. Hansen B, Miller K, Weber C. Early evidence on recreational marijuana staffed beds, hospital geographic location, diabetes, cephalosporin allergy, legalization and traffic fatalities. Econ Inq. 2018. doi:10.3386/w24417 inpatient location within the hospital, and number of infections. 4. Lane TJ, Hall W. Traffic fatalities within US states that have legalized d Includes vancomycin, fluoroquinolones, macrolides, sulfonamides, recreational cannabis sales and their neighbours. Addiction. 2019;114(5):847-856. tetracyclines, clindamycin, aminoglycosides, and linezolid. doi:10.1111/add.14536 e Includes all penicillins except antipseudomonal penicillins and first- 5. Aydelotte JD, Mardock AL, Mancheski CA, et al. Fatal crashes in the 5 years and second-generation cephalosporins. after recreational marijuana legalization in Colorado and Washington. Accid Anal f Other than antipseudomonal penicillins. Prev. 2019;132:105284. doi:10.1016/j.aap.2019.105284 g Similar when considering amoxicillin-clavulanic acid, ampicillin-sulbactam, 6. National Highway Traffic Safety Administration. Fatality Analysis Reporting and piperacillin-tazobactam together: adjusted odds ratio, 0.18 (95% CI, System (FARS) encyclopedia. Accessed November 22, 2019. https://www-fars. 0.14-0.22). nhtsa.dot.gov/States/StatesFatalitiesFatalityRates.aspx Published 2019. 1120 JAMA Internal Medicine August 2020 Volume 180, Number 8 (Reprinted) jamainternalmedicine.com © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Letters Figure. Association of Documented Penicillin Allergies With Inpatient Antibiotic Use Among US Inpatients A β-Lactam alternative antibiotic use Lesser odds Greater odds of β-lactam of β-lactam alternative alternative Infection aOR (95% CI) antibiotic use antibiotic use All 1.94 (1.74-2.17) Pneumonia 1.48 (1.13-1.95) Skin and soft tissue 1.38 (1.08-1.75) Urinary tract 2.07 (1.51-2.85) Prophylaxis for surgical procedure 7.31 (5.01-10.69) 0 2 4 6 8 10 12 aOR (95% CI) B Narrow-spectrum β-lactam antibiotic use Lesser odds Greater odds of narrow- of narrow- spectrum spectrum β-lactam β-lactam Infection aOR (95% CI) antibiotic use antibiotic use All 0.35 (0.31-0.40) Pneumonia 0.31 (0.19-0.50) Adjusted odds ratios (aORs) are Skin and soft tissue 0.53 (0.39-0.71) adjusted for age, sex, race/ethnicity, length of hospitalization, number of Urinary tract 0.26 (0.13-0.54) staffed beds, hospital geographic Prophylaxis for surgical procedure 0.11 (0.07-0.15) location, diabetes, cephalosporin 0 0.2 0.4 0.6 0.8 1.0 1.2 allergy, inpatient location within the aOR (95% CI) hospital, and number of specific infections treated. The inpatient prevalence and effects of documented peni- tients (16%) had a penicillin allergy documented in the medi- cillin allergies has been exclusively investigated in single hos- cal record. Most penicillin reactions (946 of 2112 [45%]) were pitals or health care systems. We used a large cross-sectional cutaneous. Patient characteristics by penicillin allergy status database of inpatients receiving antibiotics to assess the preva- were similar. lence and association of documented penicillin allergy with Compared with patients without a documented penicil- inpatient antibiotic use in the US. lin allergy, patients with a documented penicillin allergy had higher β-lactam alternative antibiotic use (1114 of 1741 Methods | This cohort study used cross-sectional inpatient data [64%] vs 4438 of 9251 [48%]) and lower narrow-spectrum collected through Acute Care Hospital Groups within Vizient β-lactam antibiotic use (227 of 1741 [13%] vs 2811 of 9251 Inc, Irving, Texas, from September 2018, through January 2019 [30%]). (eMethods in the Supplement). Data analysis was performed In the fully adjusted model (Table), patients with a docu- from January 2019, through January 2020. The study was re- mented penicillin allergy had increased odds of β-lactam al- viewed by the Partners Human Research Committee, Boston, ternative antibiotic use (aOR, 1.94; 95% CI, 1.74-2.17), with es- Massachusetts, and was determined to be exempt because it pecially high odds of clindamycin use (aOR, 5.34; 95% CI, 3.99- was categorized as nonhuman research. 7.13). Patients with a documented penicillin allergy had lower The exposure was an allergy to any penicillin antibiotic odds of narrow-spectrum β-lactam antibiotic use (aOR, 0.35; documented in the medical record. The outcomes were anti- 95% CI, 0.31-0.40). biotic use overall and for specified indications, considering in- The association between a documented penicillin dividual antibiotic classes and 2 antibiotic groupings: (1) β-lac- allergy and β-lactam alternative antibiotic use was stronger tam alternative antibiotics and (2) narrow-spectrum β-lactam among patients receiving antibiotics for urinary tract infec- antibiotics. tion (aOR, 2.07; 95% CI, 1.51-2.85) and as prophylaxis We examined the association of documented penicillin for surgical procedures (aOR, 7.31; 95% CI, 5.01-10.69]) allergy with antibiotic use overall and for specified indica- (Figure, A).
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