…and what to do with them
Confidence in dosing vancomycin comes from a solid understanding of vancomycin kinetics. It’s not as complicated as it seems.
I will walk you through the 3 key kinetic parameters needed to dose vancomycin:
- Elimination Rate Constant: Ke
- Half Life: T 1/2
- Vancomycin Trough & AUC
We’re not going to go back to class. We know how to get these values by dosing calculators or manual calculation. Instead we are going to focus on how to interpret and analyze these values.
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Population vs Patient Specific Kinetics
When we initially dose vancomycin we are using population kinetics. This means that we make assumptions about how the patient will metabolize vancomycin based on demographics like their age, weight and renal function because that’s how others with similar demographics metabolized it.
Once our patient has received some doses of vancomycin we can draw levels to then calculate patient specific kinetics.
This will allow us to tailor the regimen to our patient’s unique processing of vancomycin.
Let’s start with the elimination rate constant (Ke).
Vancomycin Ke
The elimination rate constant for vancomycin (Ke) is simply the amount of drug that is cleared from the body per hour.
Using Ke we can estimate the amount of drug that is present in the body after a specific period of time (T) by the equation: e-Ke(T)
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The first Ke we use will be based in population kinetics using renal function. Simply put, most patients with a creatinine clearance (CrCl) of ‘x” will eliminate vancomycin at a rate which is calculated as:
This is simply an estimate. Because CrCl is affected by many variables (weight, age, Scr, gender) 2 patients with the same value for creatinine clearance can look vastly different and metabolize vancomycin differently. There are also variations in terms of using actual body weight versus adjusted body weight for calculations of creatinine clearance. Population kinetics calculations simply provide a starting point.
We need to know Ke because it estimates how quickly vancomycin is being cleared so that we can determine when the next dose of vancomycin should be given to maintain high enough drug levels.
We do this by using Ke to determine half life (T 1/2) of vancomycin.
Vancomycin Half Life (T 1/2)
The half life of any drug is the amount of time needed for the concentration in the body to fall to 50%.
Using Ke, half life is calculated as:
We are using Ke estimated from population kinetics, therefore this half life will also be a population estimate.
0.693 is a constant that is assumed in vancomycin clearance. It assumes that vancomycin is cleared from the body in fixed proportions. This is referred to as first order clearance. It gives us a window of time, in hours, that we can use to determine the frequency of dosing.
As a general rule, the frequency of dosing should be 1-1.5 times the calculated half life to achieve vancomycin drug concentration sufficiently high to be an effective antibiotic.
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Vancomycin Dose
Once we have a frequency with which to dose, we can select a dose. This is the most straight forward part. We have a range of 15-20mg/kg per dose. You will select any dose in that range that is available at your facility.
To calculate your initial Ke, half life, frequency and dose you can use dosing calculators like vancopk.com. Remember: no calculator or protocol overrides your clinical judgment. You are solely responsible for the tools you use to treat patients.
A calculator cannot account for patient specific details like paraplegia, cirrhosis or fluctuating renal function.
To learn what to do in those situations check out the unit How to Dose Vancomycin: When Dosing Protocols Fail.
These patients have confounding clinical features that are not considered by the standard dosing tools but places them at a higher risk of vancomycin accumulation and toxicity.
Once you’ve given your initial dose at your selected frequency we will draw vancomycin levels. These levels are what will transition us from population kinetics to patient specific kinetics.
After verifying a few details we will get to see exactly how our patient clears vancomycin.
Vancomycin Trough & AUC
Through my years of practice I have worked through the transition of vancomycin monitoring via trough only to area under curve (AUC). You can see the evidence for this change in practice here.
In summary, trough only monitoring is no longer recommended when using vancomycin. The rates of efficacy and the incidence of toxicity make it less favorable to using the AUC/MIC ratio.
You will still draw trough levels but you will use them for calculation of AUC instead of a direct measurement of therapeutic efficacy.
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How to Assess Vancomycin Levels
Before you make any decision based on levels you must assess the level for accuracy.
1. Were all vancomycin doses administered?
Were any administrations missed? This can occur due to patient refusal, missing medication, compatibility issues, patient being off unit at the schedule administration time or patient intolerance to name a few. Interpretation of your results with the assumption that all doses were given when they were not can lead to significant miscalculations.
2. Were doses administered close to scheduled times?
Vancomycin administrations are time sensitive. When doses are given late it will affect the kinetics. This is especially important with every 8 hour dosing. Deviation from the dosing schedule can result in effective Q6 dosing rather than Q8 which would sway the kinetics.
3. Was the vancomycin level drawn appropriately?
Was it drawn during infusion? Immediately after the dose? Is it a true trough?
Lab errors can occur. Do not change your dose without assess the timing of the level relative to administrations.
How to Adjust Vancomycin Dose
Now that you have patient specific data we can recalculate the Ke and T1/2 for a more accurate estimate for vancomycin clearance for your patient.
We may need to change the dose, change the frequency of dosing or both depending on a combination of the blood levels, recalculated kinetic parameters and severity of infection.
1. Change the Dose
In general if you are close to goal AUC/trough you would increase the dose keeping all other factors the same.
2. Change the Frequency
If you need to double your levels to get to goal then you likely need to increase your frequency especially in serious infections like endocarditis, bacteremia and osteomyelitis.
If I increase my frequency from Q12 to Q8, more often than not, I am also going to drop my dose as well to proactively provide some buffer against variances in clearance that can lead to rapid accumulation.
The benefit of Q8 dosing is that we can get to steady state within 24 hours. Which means we can quickly increase the dose if needed while minimizing toxicity.
3. Change Dose and Frequency
Some patients in high metabolic states like cancer and trauma patients tend to clear vancomycin rapidly.
If your vancomycin level returns low (like less than 5) after verifying administration and lab times you may need to increase both factors to get to therapeutic levels.
Final Thoughts
Don’t spend weeks trying to get to goal vancomycin levels. A patient with a persistently low levels of vancomycin is effectively receiving no therapy while also increasing the risk for mutation of bacteria to vancomycin resistant species.
Using these strategies will guide you to make wise decisions that will get you to goal, minimize toxicity and improve patient outcomes.
Share some of your experiences with dosing vancomycin in the comments!
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The information on this website is intended to be used solely for educational and informational purposes. While the content may be about specific medical and health care issues, it is not a substitute for or replacement of personalized medical advice and is not intended to be used as the sole basis for making individualized medical or health-related decisions.
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