Glycopeptide antibiotics such as vancomycin are frequently utilized to treat resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus. The current literature on glycopeptide and lipoglycopeptide structure, hypersensitivity, and potential cross-reactivity was reviewed, highlighting implications for safe prescribing.

Structurally similar, glycopeptides could theoretically cross-react. Immediate reactions to vancomycin include non-IgE-mediated reactions and IgE-mediated hypersensitivity, sharing clinical features. Vancomycin can activate mast cells via MAS-related G-protein-coupled receptor X2, an IgE-independent receptor implicated in non-IgE responses. In-vivo and in-vitro testing for suspected IgE-mediated reactions to glycopeptides remains ill-defined. Vancomycin is increasingly recognized to cause severe cutaneous adverse reactions, with drug reaction with eosinophilia and systemic symptoms predominantly reported. Vancomycin DRESS has been associated with HLA-A∗32:-01, with a number needed to prevent of 1 in 74. Data demonstrating cross-reactivity amongst glycopeptides and lipoglycopeptides is limited to case reports/series.

Further studies and in-vivo/in-vitro diagnostics are required for better differentiation between IgE and non-IgE glycopeptide reactions. Despite its association with vancomycin DRESS, the utility of pharmacogenomic screening for HLA-A∗32: 01 is ill-defined. Although HLA-A∗32:01 has been associated with vancomycin DRESS, its utility for pharmacogenomic screening is ill-defined. Further clinical and immunological cross-reactivity data for glycopeptide/lipoglycopeptide antibiotics is required.