Glycopeptide Antibiotics

Overview

Glycopeptide antibiotics are a class of antimicrobial agents that inhibit bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of cell wall precursor units.

Vancomycin

Vancomycin

Mechanism of Action

  • Inhibits cell wall synthesis by binding to D-alanyl-D-alanine
  • Prevents transglycosylation and transpeptidation reactions
  • Active primarily against Gram-positive bacteria

Spectrum of Activity

Highly Active Against

  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Coagulase-negative staphylococci
  • Streptococcus species
  • Clostridium difficile (oral formulation)
  • Enterococcus species (though resistance is emerging)

Resistance Mechanisms

  • VanA, VanB, VanC gene clusters in enterococci (VRE)
  • Thickened cell wall in staphylococci
  • Altered binding sites

Clinical Applications

  • MRSA infections (skin and soft tissue, pneumonia, bacteremia)
  • Serious staphylococcal infections (penicillin-allergic patients)
  • C. difficile colitis (oral vancomycin)
  • Prophylaxis in certain surgical procedures

Adverse Effects

Common

  • Red man syndrome (histamine release, infusion-related)
  • Nephrotoxicity (especially with aminoglycosides)
  • Ototoxicity (rare, usually with high levels)

Monitoring Required

  • Serum trough levels (15-20 μg/mL for serious infections)
  • Renal function monitoring
  • Complete blood counts (bone marrow suppression rare)

Administration

  • Intravenous for systemic infections
  • Oral for C. difficile colitis (minimal systemic absorption)
  • Slow infusion over 1-2 hours to prevent red man syndrome