PK differences and Traditional Vancomycin Dosing

Which of the following statements about concentration-dependent antibiotics is or are true? The first statement is true. Therapeutic efficacy depends on achieving a high peak. That’s what we mean by concentration dependent antibiotics. Same, the B is false. Therapeutic efficacy depends on achieving a low trough that is not true. Therapeutic efficacy opinion depends on a high peak. The trough is more of a consideration for toxicity. Therapeutic efficacy depends on achieving a high AUC. That’s also false that’s a non concentration dependent drug that would depend on a high AUC in relation to the MIC. So the answer to this question is A.

Let’s summarize the pharmacokinetic differences between aminoglycosides and vancomycin. Aminoglycosides the efficacy is linked to C peak, a high peak preferably ten times greater than the MIC and we want a low trough for aminoglycosides primarily to minimize the potential for toxicity even a peak four to eight times the MIC might be suitable but 10 times the MIC provides optimal killing power against the pathogen. For vancomycin the C peak is not related to efficacy.

Efficacy and toxicity are linked to the trough level or preferably to area under the curve and actually it’s area under the curve divided by MIC, the minimum inhibitory concentration of the antibiotic against the pathogen or the area under the inhibitory curve the AUIC that might be the best measure overall. What we have to consider however, is that we also monitor the cuts the serum concentration of creatinine to assess both dosing an toxicity for both aminoglycosides and vancomycin. So we’re not just measuring peak concentrations or trough concentrations but the serum creatinine is also a very important monitoring parameter for both these antibiotics.

First of all they’re both really excreted, so changes in serum creatinine can indicate whether there might be a need to change the dose based on changing renal function. They also both have nephrotoxicity has a very significant form of toxicity, therefore, by monitoring the serum creatinine if it begins to rise that may be an indication that the drug is beginning to cause the patient toxicity. Traditional vancomycin dosing is based on actual body weight A loading dose for vancomycin is typically 25 to 30 milligrams per kilogram and the maintenance dose 15 to 20 milligrams per kilogram.

Again all patients obese or otherwise with vancomycin should be dosed on actual body weight the frequency is based on creatinine clearance because vancomycin is extensively eliminated by the kidneys. If the crediting clearance is above 90 typical dosing interval is about every eight hours from forty to eighty nine would be every 12 hours and twenty five to thirty nine would be every twenty four hours. There are variations that you’ll find in the literature but most dosing guidelines are pretty much in this ballpark. This is a dosing chart that was developed at Wanfang hospital here in Taipei. And it’s a very effective chart. You notice that it’s based on both body weight and the patient’s crediting clearance, uncorrect accredited clearance.

There is a chart that’s that appears in the literature. It was published in the journal pharmacotherapy believe it was back in 2011 that is similar and that it uses the patient’s body weight and some creatinine however that chart scales up the dosing regimen based on both creatinine and weight. If you notice the dosing ecommendations for from this Wanfang dosing chart are based primarily on the crediting clearance and as within a given crediting clearance range if you go down the column, as the patient’s weight increases the dose does not generally tend to increase and this is an optimal approach. One of the dosing nomograms that’s out there. It actually increases the dose by body weight as well as crediting clearance.

And that has a tendency to cause too much drug to be given to the patient. So this vancomycin nomogram that was developed at one from hospital is actually a very effective nomogram and it’s well substantiated in the literature. Primary target when monitoring vancomycin is the trough level which should be in the range of ten to fifteen from mild to moderate infections at fifteen to twenty four serious complicated infections. So even though where we talk about dosing by area under the curve since we can’t directly measure area under the curve, we still end up monitoring trough levels and trying to relate trough concentrations to the patient’s area under the curve.