Great work! That was probably the hardest part of your journey. We are glad you made it this far. Now that you have gotten some practice using the equations, it is time to collect some data by evaluating trough levels.
Measurements of vancomycin serum concentrations are recommended if the therapy is expected to continue for 72 hours or longer. Vancomycin is believed to display time-dependent bacterial killing; therefore, monitoring of peak concentrations is not routinely recommended. Instead, serum trough concentrations should be obtained before the next steady-state dose (~4-5 half-lives).
Therapeutic Plasma concentrations:
- Peak = 30-40 mcg/mL
- Trough = 10-20 mcg/mL
Indication | Recommended trough range |
Severe infections: | 15-20 mcg/mL |
Uncomplicated infections: | 10-15 mcg/mL |
*2020 Guideline Update Alert*
ASHP released new consensus guidelines recommending changes in vancomycin monitoring that emphasized a AUC/MIC ratio of 400-600 (assuming a MIC of 1 mg/L) over targeting a goal trough of 10-20 mcg/mL. Bayesian software programs, compared to traditional PK calculations, are recommended to evaluate daily AUC values and trough-only monitoring is not recommended. If Bayesian software is not available, AUC can also be manually calculated using first-order PK equations using two levels (peak and a trough). This change in practice will require further education to pharmacists and nurses to ensure success.
Ordering Troughs
Trough levels are drawn when the drug is expected to reach steady-state concentrations (~ 4 to 5 half-lives). This may vary between institutions, but the general rule is listed below.
Dosing interval | Trough should be drawn: |
Q8hr, Q12hr | 30 minutes prior to the 4^{th} dose |
Q24hr | 30 minutes prior to the 3^{rd} dose |
Pulse dosing or Hemodialysis | 24 hours after the loading dose then every 24-48 hours or when level is expected to be <20 mcg/mL |
In patients with Q24hr dosing intervals, serum trough concentrations are drawn before the 3^{rd} dose for earlier evaluation of drug concentrations with the understanding that the trough level is not completely at steady-state and will be higher as doses accumulate. (ex: if the level comes back 13 mcg/mL before the 3rd dose, you would not need to change the regimen as the level will be higher once serum concentrations reach steady-state)
If a loading dose is administered, it can be counted as the first dose when timing a trough level.
BACK TO DR. VANKO: Blood cultures have returned growing methicillin-resistant staphylococcus aureus (MRSA) sensitive to vancomycin. We want to continue vancomycin for at least 5 days until the first negative blood culture so we need to order a trough level.
TEST MY KNOWLEDGE
Time is Up!
Time's up
Checking Levels Earlier
Vancomycin trough levels are usually drawn at steady-state concentrations. However, there may be situations where you can check a trough earlier:
- Worsening renal function
- Clinical condition is deteriorating (e.g. fevers, leukocytosis, hypotension)
- Concerns for toxicity (e.g. acute kidney injury)
Acute kidney injury is defined as:
- Scr increase of 0.3 mg/dL over <48 hours OR
- Increase in Scr >1.5 times baseline OR
- Urine output < 0.5 ml/kg/hr for 6 hours
Evaluating Trough Levels
You have done the hard work calculating what dosing regimen to give, and now have successfully ordered and received a trough level back. Before you pat yourself on the back for a job well done or lose your cool because the trough level came back >25 mcg/mL, I want you to repeat the following:
“Was this trough drawn at the appropriate time?”
Half of all vancomycin levels are drawn either too early or too late. These incorrect levels can lead to misinterpretation and inappropriate dose adjustments.
In addition to evaluating the time the trough was drawn, it is helpful to review the previous doses to determine if administration times were appropriate (e.g., given 8 hours apart if the regimen was q8hr) as this can affect the interpretation of your trough value.
In the event that the trough was not drawn at the appropriate time, the following equation can be used to calculate an extrapolated trough.
Extrapolated trough = C_{trough} x e^{-Ket}
For example: Patient is on 1000 mg every 12 hours and the trough returned = 21 mcg/mL (drawn 2 hours early). What would the extrapolated trough be if the level was drawn on time, considering ke = 0.0084 and t is the time in hours it was drawn inappropriately (ex: 2 hours early)?
Extrapolated trough = 21 x e ^(-0.084 x 2) =18 mcg/mL (so keep cool and carry on)
If the trough was drawn 2 hours LATE instead of early, the extrapolated trough would be:
Extrapolated trough = 21 x e^(-0.084 x -2) = 25 mcg/mL
Adjusting the Regimen
There are generally two accepted methods for adjusting your dosing regimen. Method #1 utilizes patient-specific kinetics to determine a new dose and interval that will get the patient to therapeutic goals. Since vancomycin follows linear kinetics, Method #2 can also be used to determine a new dosing regimen. Let’s take a look at both.
Method #1:
K_{e }= (-) ln {(C_{trough }x Vd / dose) / [ 1 + C_{trough} x Vd / dose)}
Dosing interval (T)
Before, we were using an estimated population kinetics to determine a dose for the patient. Now that we have a measured trough level, we can calculate the patient’s specific elimination constant (K_{e}) to determine the new dosing regimen.
Once you have obtained the patient’s specific elimination constant, you plug it into the same vancomycin equations previously discussed to determine a new maintenance dose and interval.
Method #2:
Since vancomycin follows linear kinetics, ratio and proportions can be used to determine the new dose or X.
Dose = New dose (X)
Trough obtained Goal trough
Since vancomycin follows linear kinetics, ratio and proportions can be used to determine the new dose or X.
Example: Dose is 1250 mg every 12 hours and measured trough 10 mcg/mL drawn at the appropriate time.
New dose is: 2500/10 = x /15 x = 3750 mg so the new dosing regimen will be 1250 mg q8hrs (3750 mg/3)
The general rule of thumb is if your trough level is way off from your goal, like the example above, adjust your interval. However, if your trough level is closer to your goal, then adjust the maintenance dose.
Trough levels | Recommendation |
Very low (e.g. <10 mcg/mL) | A new loading dose may be given and the interval will need to be shortened |
High 20-25 mcg/mL | Decrease the dose or interval |
Very high >26 mcg/mL | Hold the dose of vancomycin and draw a random level in 24 hours. If level returns <20 mcg/mL, consider re-initiating vancomycin at a lower dose or longer interval |
TEST MY KNOWLEDGE
Time is Up!
Time's up
You’re mighty impressive! Now it’s time to complete the FINAL quiz and help Dr. Vanko escape the lab. Hurry before it is too late!