Vancomycin in Clinical Practice: Roles, Resistance, and Future Directions

Abstract

Vancomycin remains a leading glycopeptide antibiotic in the treatment of serious Gram-positive infections but its long-term clinical utility is limited by antimicrobial resistance (AMR). In this review we discuss vancomycin as a problem-based case study in antimicrobial stewardship: how can a long-established antibiotic continue to be effective in clinical practice while its bacterial adaptation is decreasing, and vice versa? The molecular structure and D-Ala-D-Ala target recognition of vancomycin are related to its cell-wall inhibition and clinical role, therapeutic monitoring and major resistance phenotypes. We focus on the role of van gene clusters and different resistance strategies for vancomycin-resistant enterococci (VRE), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant S. aureus (VRSA). The evidence suggests that preserving vancomycin needs to do more than just develop replacement drugs: proper clinical use, therapeutic monitoring, local resistance surveillance, infection control and continued development of modified glycopeptides and complementary therapeutic strategies are needed. Vancomycin thus represents a broader principle of antimicrobial therapy: that an antibiotic is durable if molecular innovation is integrated with the right clinical use.