Redefining Diagnostic and Management Approaches to Vancomycin Adverse Drug Reactions

Vancomycin remains a cornerstone therapy for resistant gram-positive infections, yet adverse drug reactions are common and often mislabeled, leading to unnecessary avoidance and downstream negative consequences. This review summarizes the epidemiology, mechanisms, diagnostic tools, and management strategies to support mechanism-based care. Vancomycin infusion reaction, likely driven by Mas-related G-protein coupled receptor X2, is the most common vancomycin-induced hypersensitivity phenotype, whereas IgE-mediated reactions are rare and remain mechanistically unproven. Diagnostic limitations are substantial, because reactions can be clinically identical and distinguishing biomarkers or diagnostic tools are lacking. Dose-response intradermal testing for vancomycin infusion reaction evaluation is an emerging approach. Vancomycin infusion reaction management focuses on supportive therapy and adjustment of the infusion rate, whereas recurrent or severe reactions should prompt allergy evaluation for a possible IgE-mediated mechanism. Delayed reactions are less well characterized and span a spectrum from benign morbilliform eruptions to severe cutaneous adverse reactions, most notably drug reaction with eosinophilia and systemic symptoms. Diagnostic testing for delayed reactions remains limited, with no validated skin testing methods and in vitro assays restricted to research settings. Continued advances in understanding immunologic mechanisms, together with standardized electronic health record terminology and delabeling pathways, are essential to improve diagnostic accuracy and strengthen antimicrobial stewardship.