In this episode, I’ll discuss why the new vancomycin guidelines made the switch to AUC/MIC based dosing.
Shout out to “Pharmacy Hany” for inspiring this episode.
A trough is only a single point estimate of drug exposure at the end of the dosing interval, while AUC/MIC refers to the area under the concentration curve in a 24 hour period divided by the minimum inhibitory concentration.
While in practice it has been routine to use the trough level to guide vancomycin dosing, it has always been the AUC/MIC that is known to correlate well with clinical cure.
Even the 2009 vancomycin guidelines acknowledged that it is the 24-hour AUC/MIC value that is correlated with clinical outcomes for vancomycin. The trough value was used instead because the authors thought it was more practical and that it roughly correlated to the appropriate AUC/MIC:
Vancomycin displays concentration-independent activity against S. aureus, with the area under the concentration curve (AUC) divided by the MIC as the primary predictive pharmacodynamic parameter for efficacy. On the basis of in vitro, animal, and limited human data, an AUC/MIC value of 400 has been established as the pharmacokinetic-pharmacodynamic target.
Trough serum vancomycin concentrations in [the] range [of 15-20 mg/L] should achieve an AUC/MIC of >400 for most patients if the MIC is <1 mg/L
When using a trough range of 15-20 mg/L, one is essentially guaranteed of achieving an AUC/MIC of >400. This is because a trough of 15 mg/L represents a 24-hour AUC of 360, and since the peak level is much higher than 15 mg/L, the additional area under the concentration curve will always add up to above 400.
The trouble with this method is that although it guarantees meeting the AUC/MIC target of 400, the AUC/MIC value may be well in excess of 400. This means that additional toxicity risk is undertaken when using the convenience of dosing by trough value instead of AUC/MIC.
New vancomycin guidelines were published in March 2020. These guidelines have recommended that AUC/MIC be used to monitor vancomycin instead of trough values.
The new guideline authors site both retrospective and prospective evidence that suggests kidney toxicity from vancomycin can be reduced by using an AUC/MIC approach to dosing instead of trough values.
In addition, the availability of first-order pharmacokinetic calculators, possibly even embedded in the electronic medical record and bayesian dosing methods that can guide AUC/MIC dosing are now readily available.
This means the trade-off of simplicity for toxicity that trough values represent is no longer justifiable in the opinion of the guidelines authors.
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I think the guidelines got it wrong in regards to critically ill patients. I am not aware of any, let alone strong, data to support AUC:MIC dosing in ICU patients. If anything, ICU patients should be receiving continuous vancomycin, if lines permit, given it is easier on the beans with more stable kinetics versus intermittent dosing. There are numerous published protocols for CIV vancomycin in critically ill patients. Furthermore, we can more easily calculate AUC using CIV vancomycin simply by multiplying our Css level by 24hr.
Great points Ruben, thank you!