A 55-year-old man with MRSA bacteraemia shows an initial vancomycin E-test MIC of 1 mg/L, but after two weeks of therapy blood cultures remain positive and the MIC has risen to 8 mg/L while the teicoplanin MIC stays low. The most likely underlying mechanism is:
- A Replacement of D-Ala-D-Ala termini with D-Ala-D-Lac by acquired ligases
- B Thickening of the cell wall peptidoglycan with excess free D-Ala-D-Ala residues that trap vancomycin before it reaches the division septum ✓
- C Plasmid-borne mcr-type modification of wall teichoic acids
- D Loss of the autolysin Atl, preventing drug-induced cell lysis
Correct answer: B. Thickening of the cell wall peptidoglycan with excess free D-Ala-D-Ala residues that trap vancomycin before it reaches the division septum
Explanation
Vancomycin-intermediate S. aureus (VISA) arises through stepwise mutations that thicken the peptidoglycan layer and increase exposed free D-Ala-D-Ala dipeptides, which bind and sequester vancomycin in the outer wall so it never reaches its lethal target at the septum. True target replacement by D-Ala-D-Lac is the vanA mechanism seen in enterococci, not in staphylococci, and it raises teicoplanin MICs as well. Wall teichoic acid mcr-type modification does not exist, making option C a fabricated mechanism.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.