Vancomycin

Background

• A glycopeptide antibiotic

Mechanism of action

• Inhibits cross-linking of peptidoglycans in the cell wall

Pharmacodynamics

• Efficacy predicted by AUC to MIC ratio

Indications

• Suspected or confirmed MRSA

Dosing

• Common dose
  • Loading dose of 25-30 mg/kg given once for serious infections
  • 15 mg/kg/dose with timing based on renal function (q12h if normal)
  • Titrate based on monitoring parameters (below)
  • Adjustments assume linear pharmacokinetics,so a doubling of the daily dose, for example, should double the trough or AUC:MIC

Obesity

• Dosing should use actual body weight, with a maximum loading dose of 3 g

Monitoring

• Based on PK/PD modelling, the trough level was previously used to dose vancomycin
  • Serum trough drawn within hour before fourth dose
  • 10-15 for low-risk infections
  • 15-20 for high-risk Staphylococcus aureus infections such as osteomyelitis, meningitis, and bacteremia
• Current guidelines recommend AUC:MIC monitoring using Bayesian calculators1
  • Use peak 60 min after infusion and trough 1 to 60 minutes before next dose, and record times accurately
  • Target AUC/MIC_BMD ratio of 400 to 600 for serious Staphylococcus aureus infections

Adverse Reactions

• Primarily include renal failure and red person syndrome

Renal Failures

• Risk factors
  • Prolonged courses >21 days
  • Higher trough
  • Concomitant nephrotoxic medication
  • Older age
  • CKD/AKI
  • Liver disease
  • Peritonitis
  • Neutropenia
  • Male sex
• Mechanism of injury: oxidative stress in the proximal tubular cells

Red Person Syndrome

• Rash, pruritis, and hypotension, with onset of vancomycin, resolves on stopping
• Very high incidence previously
• Histamine-mediated
• Can decrease dose or prolong infusion, prophylactic antihistamines