Like methicillin, vancomycin exerts its antimicrobial effect by inhibiting cell wall synthesis, binding irreversibly to cell wall precursors – D-alanyl-D-alanine; and attacking sites responsible for cell wall synthesis.
Resistance in VISA strains is thought to be due to:
- Accelerated peptidoglycan synthesis with increased quantities of D-alanyl-D-alanine residues, which bind & sequester vancomycin molecules
- Thicker cell walls with reduced peptidoglycan cross-linking (impedes progress of drug molecules)
- Increased glutamine mucopeptides
All strains with MIC ≥4 µg/mL should be considered candidate VISA strains.
Cell wall thickening and transfer of genetic material underlie the development of vancomycin resistance. There is evidence to support the transfer of genetic material among vancomycin-resistant bacterial isolates; the Michigan (2002) VRSA isolate acquired the vanA gene via interspecies transfer from a co-isolated vancomycin-resistant Enterococcus faecalis.
