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 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 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
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
- Primarily include renal failure and red person syndrome
Renal Failures
- Dose-dependent risk, with significant increase with trough over 15
- Lower risk with AUC-based dosing, which promotes lower dosing, and with continuous infusion
- Risk factors: prolonged courses >21 days, higher troughs, concomitant nephrotoxic medication, older age, CKD/AKI, liver disease, peritonitis, neutropenia, and male sex
- Mechanism of injury: either AIN or ATN from 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.