Vancomycin: Difference between revisions

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**[[Weissella]]
**[[Weissella]]


===Pharmacodynamics===
===Pharmacokinetics and Pharmacodynamics===


*Bactericidal
*Efficacy predicted by AUC to MIC ratio
*Concentration-independent with post-antibiotic effect
*Efficacy predicted by AUC<sub>24</sub>:MIC


===Clinical Breakpoints===
===Clinical Breakpoints===
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**Concomitant nephrotoxic medication
**Concomitant nephrotoxic medication
**Older age
**Older age
**CKD/AKI
**[[CKD]]/[[AKI]]
**Liver disease
**[[Liver disease]]
**Peritonitis
**[[Peritonitis]]
**Neutropenia
**[[Neutropenia]]
**Male sex
**Male sex
*Mechanism of injury: oxidative stress in the proximal tubular cells
*Mechanism of injury: oxidative stress in the proximal tubular cells

Revision as of 10:13, 28 September 2020

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 S. aureus ≤4 8-16 ≥32
Enterococcus species ≤4 8-16 ≥32
Streptococcus pneumoniae ≤1
β-hemolytic streptococci ≤1

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/MICBMD ratio of 400 to 600 for serious Staphylococcus aureus infections

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

References

  1. ^  Michael J Rybak, Jennifer Le, Thomas P Lodise, Donald P Levine, John S Bradley, Catherine Liu, Bruce A Mueller, Manjunath P Pai, Annie Wong-Beringer, John C Rotschafer, Keith A Rodvold, Holly D Maples, Benjamin M Lomaestro. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020. doi:10.1093/ajhp/zxaa036.