Vancomycin "allergy” labels in the EHR: Defining Epidemiology, Outcomes and Genetic risk

Abstract

Prof.RATIONALE: Vancomycin is recognized to be associated with ''allergy labels'' (VAL) in the electronic health record; however, clinical distribution and knowledge of host predisposition across distinct clinical phenotypes are lacking. METHODS: BioVu, a DNA Biobank paired with a deidentified EHR was used to review VAL. We included subjects with multiethnicity genotyping array (MegaEx) typing with HLA ABC DR DQ DP imputed by SNP2HLA. We interrogated specific VAL phenotypes for HLA associations, concurrent allergy labels, and outcomes compared with age, sex, race and disease matched vancomycin tolerant controls (conditional logistical analyses, R version 4.0.3) Bonferroni controlled for multiple comparisons. Where VAL phenotype sample size >100 , we performed MegaEx genome wide association studies (GWAS). RESULTS: 1020/3076236 (0.33%) BioVu MegaEx VAL patients were identified (non-IgE mediated reactions (Redman) type reactions (42%), nephrotoxicity (6.2%) cytopenias, and potential hypersensitivity reactions (15.7%). Those with Redman-type reactions were younger 40 IQR [23, 61] vs. 55 IQR [40, 67], p<0.0005. HLA-A*32:01, previously associated with vancomycin DRESS, was equally represented across the entire VAL group (67/1017 (6.59%) and BioVu MegaEx population 5634/94179 (5.98%)), but was less common in VAL nephrotoxicity group (1/42 (2.38%), driven by higher prevalence of African Americans in vancomycin-piperacillin tazobactam nephrotoxicity group (4/77 (5.2%) vs. 12/587 (2.0%) European-Americans, p50.08.). Cluster and network analyses from HLA and MegaEx data identified significant phenotype-genotype relationships. CONCLUSIONS: VAL are complex and heterogeneous clinical phenotypes that can be defined by epidemiological and genetic differences. Non-IgE mediated reactions, the most common, remain a permanent part of the EHR despite their modifiability.