Advantages of Vancomycin continuous infusion and Traditional AMG dosing

A patient is receiving 1,000 milligrams of vancomycin every 12 hours Clarence’s 2.0 liters per hour and the MIC is 2 milligrams per liter. A is true. The area under the curve for 24 hours is 1,000 milligram hours per liter. Simply the daily dose which is 2,000 milligrams divided by the clearance 2.0 liters per hour. B is also true the area under the inhibitory curve is 500 because we have an AUC 24 of a thousand divided by the MIC of 2 milligrams per liter. The dosing regimen is likely to be both safe and effective. That’s a false statement.

It’s likely to be effective because the AUIC is over 400 but the AUC 24 is greater than 700 which puts us in an increased risk for nephrotoxicity. So the answer to this question is D. A and B are correct but C is not. There are some potential advantages to administering vancomycin by continuous infusion based on the fact that we’re pursuing an area under the curve and the easiest way to obtain a consistent area under the curve is to give a continuous infusion. In this example patient can receive 750 milligrams every 8 hours and this would provide a C trough of fifteen point three milligrams per liter.

However if we were to give the patient a continuous infusion at the same daily dosing rate that infusion rate would be 94 milligrams per hour. The Css the concentration at steady-state once that blue curve plateaus is twenty three point four milligrams per liter In the area under the curve for 24 hours is 562 milligram hours per liter. Now note how easy it is to accurately calculate an area undethe curve for 24 hours when the patient has plateaued on a continuous infusion We literally have a rectangle. We can multiply by the 24 hours times the serum concentration to get a very accurate AUC 24. Dosing by a continuous infusion of vancomycin is very common in Europe.

It’s not done very much in the United States; it’s not done a great deal in Asia but it’s very common in Europe. It’s the studies on continuous infusion vancomycin have shown that there’s comparable efficacy and to some extent less toxicity. What’s nice about it is there’s no need for trough monitoring.There are actually no trough levels. With continuous infusion, you wait till the patient is at steady state and you measure an accurate Css concentration. The Css is reliably measured when the patient’s is steady-state and we can determine an accurate AUC 24 by simply multiplying the Css by 24.

All dosing adjustments are linear so it’s very easy to increase the Css to whatever the desired value is by simply making a proportionate adjustment in the infusion rate. The loading dose for continuous infusion and studies has generally been about 15 to 20 milligrams per kilogram and by looking at the graph on this slide I think it illustrates why a loading dose is much more important when a patient is going to be started on a continuous infusion than a multiple dosing regimen.

And note with the read multiple dosing serum concentrations you can see that even though the first dose is is considerably lower than the C MAX it still provides a fairly significant serum concentration whereas when a patient starts on a continuous infusion Patient starts at zero and it takes quite a while for the serum concentration to even get up above ten or fifteen milligrams per liter. So for continuous infusion serious consideration should be given to giving the a loading dose. Also there needs to be consideration about Y-site compatibility if the patient is going to be receiving other drugs through the same line that the vancomycin is running in.

This chart was developed in an article published by Waineo in the journal of clinical pharmacy and therapeutics back in 2015 and it provides specific guidelines using a similar process to the what was used to develop the dosing chart by Wan Fong hospital. It’s a similar process simply targeting a particular CSS or an AUC 24 and either the daily dose or the hourly infusion rate that would be designed to achieve that based on the patient’s crediting clearance. Now let’s shift gears and consider aminoglycosides. This is standard interval dosing for amino glycosides. Generally we measure a peak, however, we can’t measure a peak immediately at the end of an infusion.

If a patient receives a 30-minute infusion of vancomycin as is often the case, it takes time for the drug to distribute. So we don’t actually measure a peak right at the end of the infusion, generally wait 30 minutes or so or an hour after the end of the infusion to measure a peak level. So the distribution has already been completed that distribution phase. So the true peak would occur at the end of the infusion and the measured peak is sometime thereafter.

We can designate that time interval from the end of the infusion to when the peak would be measured as T Prime and the trough is measured sometime before the next dose generally within 30 minutes of that next dose and so the time from the trough to the next infusion can be designated as t double prime. So when we’re dealing with amino glycosides levels to determine the elimination rate constant for the patient, we need to calculate the the slope of the natural log curve between the measured peak and the measure trough.

The time interval there would be the dosing interval minus the infusion time minus the time from the end of the infusion to the peak level minus the time from the trough to the next infusion. It’s very important when you’re dealing with the minimum glycoside serum levels to understand all the timing implications of when the peak and when the trough levels were measured. The dosing of aminoglycosides for standard interval dosing, it’s generally based on ideal body weight or if the patient is obese and adjusted body weight using 0.4 times the actual body weight minus ideal body weight added back to the idea of body weight per standard interval dosing the dose ranges generally from 1 to 2 milligrams per kilogram.

and the frequency based on crediting clearance milliliters per minute is generally every eight hours if it’s above or equal to 85 every 12 hours and the 50 to 84 range and every 24 hours in the 30 to 49 range again based on grinding clearance and milliliters per minute. The primary target for standard interval dosing which would be Q 8 hours for patients with normal renal function would be a peak in the range of 4 to 10 and a trough of less than 2. Now again the idea of the peak is to achieve a high concentration at least four to eight times the MIC and to keep the trough below two for reasons of avoiding toxicity.

The peak is to provide killing power against the pathogen.