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 and 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 or VRSA strains and should be sent to a reference laboratory for confirmation.
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.
