Vancomycin

From IDWiki

Background

Mechanism of Action

  • Inhibits cross-linking of peptidoglycans in the cell wall

Mechanisms of Resistance

  • Alterations in peptidoglycans conferred by chromosomal or plasmid-mediated vanA, vanB, or vanC

Spectrum of Activity

Pharmacokinetics and Pharmacodynamics

  • Bactericidal
  • Concentration-independent with post-antibiotic effect
  • Efficacy predicted by AUC24:MIC

Clinical Breakpoints

Species Breakpoints (μg/mL)
S I R
Staphylococcus aureus ≤2 4-8 ≥16
Staphylococcus species other than Staphylococcus aureus ≤4 8-16 ≥32
Enterococcus ≤4 8-16 ≥32
Streptococcus pneumoniae ≤1
β-hemolytic streptococci ≤1

Dosing

Intermittent Infusion

  • 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

Renal Dosing

  • CrCl >100 mL/min: 15-20 mg/kg q8-12h
  • CrCCl 50 to 100: 15-20 mg/kg q12h
  • CrCl 20-49: 15-20 mg/kg q24h
  • CrCl <20: 15-20 mg/kg q48h
  • Hemodialysis: target pre-dialysis levels of 15 to 20
    • If next HD in 1 day, give 15 mg/kg
    • If next HD in 2 days, give 25 mg/kg
    • If next HD in 3 days, give 35 mg/kg
    • Give at rate of 15 mg/min over the last 120 minutes of HD to coincide with the end of dialysis
    • Alternatively:
      • < 70 kg: 1000mg IV x 1, then 500mg post-dialysis
      • 70 –100kg: 1250mg IV x 1, then 750mg post-dialysis
      • >100 kg: 1500mg IV x 1, then 1000mg post-dialysis
  • CAPD: 7.5 mg/kg q48-96h
  • CRRT: 10-15 mg/kg q24-48h

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 calculatorsrybak2020th
    • Use peak 60 min after infusion and trough 1 to 60 minutes before next dose, and record times accurately
    • Target AUC/MICBMD ratio of 400 to 600 for serious Staphylococcus aureus infections

Continuous Infusion

  • Particularly useful in the following patients:
    • Total daily doses of 4 g or higher, since it will lower the total dose and therefore associated toxicitynephro
    • Home antibiotic therapy, to simplify drug monitoring
  • At least as safe and effective as intermittent infusion
  • Limited by pump availability and IV access
  • Consider loading dose in patients who are not already on intermittent infusion and who are hemodynamically unstable
  • Initial dose based on creatinine clearance and weight
TBW (kg) CrCl (mL/min) Load (mg) Maintenance (mg/24h)
<100 ≥90 1000 2000
100-119 1500 2500
≥120 2000 3000
Obesity and Renal Failure
100-115 70-89 1000 1750
50-69 1000 1250
40-49 1000 1000
30-39 1000 750
20-29 1000 500
116-139 70-89 1250 2000
50-69 1250 1500
40-49 1250 1250
30-39 1250 1000
20-29 1250 750
140-159 70-89 1500 2500
50-69 1500 1750
40-49 1500 1500
30-39 1500 1250
20-29 1500 750
160-179 70-89 1500 2750
50-69 1500 2000
40-49 1500 1500
30-39 1500 1250
20-29 1500 1000
180-199 70-89 1750 3000
50-69 1750 2500
40-49 1750 2000
30-39 1750 1500
20-29 1750 1000

Monitoring

  • Random vancomycin levels
    • First level is 24 hours after starting
    • Monitor weekly, any time the patient is unstable, and 24 hours after any dose adjustments
    • Target levels are typically 15 to 20
  • Serum creatinine should be measured twice weekly
  • CBC monitored weekly

Adverse Reactions

Renal Failures

  • Risk factors
  • 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