In this episode, I’ll discuss whether allometric dosing of vancomycin is likely to achieve AUC/MIC ratio over 400.
In episode 193, I discussed an article about allometric dosing of vancomycin. In a single-center retrospective study, the allometric vancomycin dosing regimen achieved therapeutic vancomycin concentrations 77% of the time. One of the limitations the authors of this study noted was that they were unable to assess the AUC:MIC ratio for vancomycin achieved with the allometric dosing regimen.
Joint guidelines on dosing vancomycin were published by the Infectious Disease Society of America and the Association of Health Systems Pharmacists in 2009.
The vancomycin trough goal in these guidelines of 15-20 mg/L in serious infection was controversial when it came out in 2009 and remains so today.
This goal was proposed as a way to ensure that patients achieve the ideal 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC) of at least 400. However, analyses have demonstrated that patients with adequate renal function can typically achieve the AUC:MIC goal with a more conservative trough concentration. In addition, measures of cure with vancomycin are correlated to the AUC:MIC ratio achieved, not the trough level.
The predicted AUC:MIC ratio for a vancomycin dosing regimen can be predicted in advance by a simple formula:
First, divide the total daily dose of vancomycin by the estimated clearance of vancomycin. Then divide this number by the MIC. The formula can be expressed as this: ((daily vancomycin dose)/(ClCr*0.75*0.06))/(MIC). Clearance of vancomycin is about 75% of creatinine clearance and this is multiplied by 0.06 to convert to L/hour.
I’ve created a calculator to do this estimation here.
In order to determine if allometric dosing of vancomycin is likely to achieve AUC/MIC ratio over 400, I performed a Monte Carlo analysis, similar to the one from episode 186 about rocuronium & ketamine.
I simulated 5000 patients based on the average and standard deviation for weight and creatinine clearance reported in the allometric vancomycin study.
I eliminated about 830 simulated patients whose weight was under 50 kg or creatinine clearance was under 25 mL/min. I rounded the allometric dose of vancomycin to the nearest 100 mg just like in the allometric study.
Then, for each simulated patient, I estimated the AUC/MIC ratio for MIC values of 0.5, 1, 1.5, and 2.
The AUC/MIC was predicted to be above 400 as follows:
100% for patients with MIC of 0.5
99.7% for patients with MIC of 1
88.1% for patients with MIC of 1.5
55% for patients with MIC of 2
Since many institutions round vancomycin doses to the nearest 250 mg instead of the nearest 100mg, I repeated the analysis using allometric dosing that was rounded to the nearest 250 mg.
The AUC/MIC was predicted to be above 400 as follows:
99.98% for patients with MIC of 0.5
99.5% for patients with MIC of 1
87.4% for patients with MIC of 1.5
55.9% for patients with MIC of 2
This analysis is limited by the fact that I only used weight and creatinine clearance to simulate patients. A more accurate analysis would simulate patients using gender, weight, height, and serum creatinine. In addition, I used a fixed calculation for vancomycin clearance of 75% of the creatinine clearance. Vancomycin clearance can vary widely and be dependent on other factors such as obesity.
I conclude based on this analysis that calculating an initial vancomycin dosing regimen using the allometric formula proposed by Brown and colleagues is likely to result in an acceptable percentage of patients with an AUC/MIC ratio >400 for MICs 1.5 and below.
You can access the excel file that I used to perform this analysis in my download area by clicking here to sign up for a free pharmacyjoe.com account.
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