Vancomycin: Difference between revisions
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*Mechanism of injury: oxidative stress in the proximal tubular cells |
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Revision as of 06:13, 28 September 2020
Background
- A glycopeptide antibiotic
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
- Broadly active against Gram-positive bacteria, including anaerobes
- Not active against Gram-negative bacteria
- Notable resistance occurs in:
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
- 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
References
- ^ 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.
