Skip to 0 minutes and 14 seconds Welcome back to clinical applications of pharmacokinetic dosing and monitoring. This is session five. What pharmacists need to know about dosing aminoglycosides and vancomycin The question we’ll try to answer in this video is how can we optimize efficacy and minimize toxicity when dosing vancomycin or aminoglycosides. This fifth session provides some basic information some basic principles of dosing vancomycin and aminoglycosides and the sixth session, the final session of this course will include a pharmacist who’s practicing here right here in taipei at Wanfang Hospital, talking about some actual case studies of dosing vancomycin and aminoglycosides. But in this lesson when it’s completed you should be able to explain how the pathogen killing pattern is different between aminoglycosides and vancomycin.
Skip to 1 minute and 14 seconds Determined vancomycin dosing based on area under the curve twenty-four MIC and crediting clarence explained the target serum levels for vancomycin and aminoglycosides and how to interpret those serum levels. Described how to dose vancomycin by continuous infusion and distinguish between standard and extended interval aminoglycosides dosing and dose aminoglycosides using the Hartford nomogram. Let’s begin by considering the pharmacokinetic and pharmacodynamic aspects of treating infections what we’re really talking about is a three-way fight, starting with a patient and how the patient interacts with the bacteria that have caused the infection. The patient has an immune system that can fight the bacteria and the bacteria has pathogenic mechanisms that cause illness in the patient based on the infection.
Skip to 2 minutes and 21 seconds We then have the antibiotic that comes into play, in support of the patient. The antibiotic provides drug therapy to kill the bacteria and the bacteria tries to develop resistance against the antibiotic but the antibiotic can also have side effects or toxicities that affect the patient so you have this three-way battle going on between the antibiotic, the patient and the bacteria and the role of the pharmacist is to try to do as much as possible to make sure that the bacteria is killed and the patient is not harmed and recovers fully from the infection.
Skip to 3 minutes and 7 seconds Let’s consider the killing type of the antibiotic and using fighting or boxing as an analogy we can refer to the punching type of an antibiotic. Some antibiotics are concentration dependent. They provide a big knockout punch and for those antibiotics what we need is a very high concentration well above the MIC or the minimum inhibitory concentration for the organism against that antibiotic. In this case aminoglycosides our concentration dependent antibiotics they function by achieving a very high peak concentration that knocks out the antibiotic the pathogen Time dependent antibiotics are a little different. They don’t succeed with a big knockout punch.
Skip to 4 minutes and 3 seconds They they wear down the pathogen more like a body puncher in boxing by keeping the serum concentration above the MIC for much of a dosing interval. So it’s more related to the time in which the serum level is above the MIC rather than having a very very high serum concentration way above the MIC, as the concentration dependent antibiotics Penicillins and cephalosporins are examples of time dependent antibiotics in which it’s the time above the MIC that is most important. And the non concentration-dependent antibiotic relates more to the overall area under the curve of the antibiotic. Particularly the portion of the area under the curve that is above the MIC.
Skip to 4 minutes and 57 seconds An example of this type of antibiotic is vancomycin so it also where’s the pathogen down by keeping heavy exposure above the MIC.
Skip to 5 minutes and 11 seconds Here’s an example of the aminoglycoside concentration dependent nature and notice to the right of the yellow line on this histogram. When the peak to MIC ratio is at least 10 we have a very high response rate. And above that the response rate doesn’t increase very much. So if you have a serum concentration a peak serum concentration more than ten times the MIC, that means you’re really getting a big knockout punch factor for the immediate glycoside. But even at an MIC peak the MIC ratio of four to eight, there’s still a fairly significant response rate for the antibiotic.
Skip to 6 minutes and 1 second Now contrast this to antibiotics that are more time dependent or it’s the time above the MIC that relates more to the effectiveness of the antibiotic you can see that when the time above the MIC is greater than about 50 percent of the dosing interval which is shown by the red line then there’s there tends to be a plateau effect in terms of the bacterial logic cure rate. These are for drugs like trimethoprim sulfamethoxazole or macrolides or beta lactam, drugs, their time dependent. Then we have the non concentration dependent drugs like vancomycin where what really matters is the area under the curve that’s above the MIC. This is referred to as the area under the inhibitory curve shown on the graph
Skip to 7 minutes and 2 seconds which is essentially area under the curve divided by MIC is the area under the inhibitory curve. What’s been shown is that when therapy is prolonged with a very low area under the inhibitory curve, this increases the likelihood of resistance . In this graph, particularly when the area under the inhibitory curve was less than a hundred you can see that at five days of therapy there was beginning to be quite a drop-off and as the therapy continued for ten or fifteen days there’s more and more resistance.
The ideas pharmacists need to know about dosing Aminoglycosides and Vancomycin
How can we optimize efficacy and minimize toxicity when dosing aminoglycosides and vancomycin?
Based on pharmacokinetic and pharmacodynamic considerations, we can understand the importance of the killing type of an antibiotic. For instance, Aminoglycosides is concentration-dependent. On the contrary, Penicillin and Cephalosporins are time-dependent.
We can also learn the effect of “peak/ MIC” for a concentration-dependent drug, and the effect of “time above MIC” for a time-dependent drug.
Have you faced any related problems in your job or your study? Please share your experience below.
Please check the related file for week 5 course slides for your reference.
Prof. Daniel L. Brown