What is the mechanism of action of vancomycin and a major toxicity concern?

• A. Inhibits cell wall synthesis by binding D-Ala-D-Ala; nephrotoxicity and ototoxicity; red man syndrome can occur with rapid infusion.
• B. Inhibits bacterial DNA gyrase; photosensitivity.
• C. Inhibits protein synthesis at 50S; causes rash.
• D. Disrupts cell membrane proton motive force; tinnitus.

Answer: (A)

Vancomycin works by directly blocking the construction of the bacterial cell wall. It binds to the terminal D-Ala-D-Ala sequence of peptidoglycan precursors, preventing the enzymes that cross-link the wall from functioning. Without a proper, cross-linked cell wall, Gram-positive bacteria cannot withstand osmotic pressure and are effectively killed.

A major toxicity concern is damage to the kidneys and ears, so nephrotoxicity and ototoxicity are important monitoring considerations. Additionally, rapid IV administration can trigger red man syndrome, a histamine-mediated infusion reaction rather than a true allergy. Vancomycin is mainly active against Gram-positive organisms, which is why it’s used for MRSA and certain severe Clostridioides difficile infections (the latter typically treated orally for intestinal infection).