Vancomycin

Summary

Vancomycin is an antibiotic primarily used to treat infections by gram-positive bacteria. It works to block bacterial cell wall synthesis, by binding to a D-Ala-D-Ala sequence on the ends of the peptidoglycans that make up the cell wall. Bacteria can develop resistance to vancomycin by mutating D-Ala-D-Ala to a D-Ala-D-Lac sequence. Clinically, vancomycin is used for treating gram-positive bacteria, especially for staphylococcus and for clostridium difficile. Side effects of vancomycin include nephrotoxicity, ototoxicity and red man syndrome. Red man syndrome is mediated by histamine release, and can be prevented by predosing with antihistamines.

Key Points

• Vancomycin
  • Mechanism
    • Inhibits cell wall synthesis in bacteria
      • By binding D-Ala-D-Ala portion of cell wall precursors
      • Inhibits cross-linking between the building blocks (peptidoglycans) that make up the bacterial cell wall
    • Bactericidal (against most bacteria)
      • Bacteriostatic against C. difficile
  • Clinical Use
    • Broad gram-positive coverage
      • Usually reserved for infections resistant to other drugs
      • MRSA
      • Clostridium difficile (oral formulation)
      • S. epidermidis
      • Sensitive Enterococcus species
  • Adverse Effects
    • Flushing (Red Man syndrome)
      • Mediated by histamine (pseudo-allergic reaction) from mast cells, in an fashion not dependent on IgE signaling
      • Preventable with pre-treatment with antihistamines
    • Nephrotoxicity
    • Ototoxicity
    • Thrombophlebitis
    • DRESS syndrome
  • Mechanism of Resistance
    • Not susceptible to beta-lactamases
      • Not a beta-lactam drug
    • Amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac
      • Switches an Alanine residue to a Lactate, preventing binding by vancomycin
      • Seen in vancomycin-resistant enterococcus (VRE)