How do you handle AUC monitoring in the transition to outpatient parenteral antibiotic therapy (OPAT)?
Consider putting specific recommendations in the discharge summary recommending specific trough goals for patients that were dosed by AUC while inpatient (e.g., "Please maintain trough ~12-15 and do not target a trough of 15-20 as this patient was found to have an AUC of 500 on a dose of 1g q12h with a corresponding trough of 13")
Is AUC-based vancomycin dosing appropriate for central nervous system (CNS) infections?
There is a lack of sufficient data to recommend a specific AUC for CNS infections.
Is AUC-based vancomycin dosing appropriate for skin and soft tissue infections (SSTI)?
There is a lack of sufficient data to suggest a specific AUC for SSTI. A recent research study demonstrated that an AUC above 400 is associated with better outcomes (Aloisaimy, S et al. Clin Infect Dis. 2020), however, additional validation is needed. The choice to perform vancomycin TDM in these patients can depend on planned duration. If treating for longer than 3-5 days, monitoring should be performed.
If targeting an organism other than MRSA, should AUC-based dosing be used?
There is a lack of sufficient data to recommend a specific AUC for infections caused by organisms other than MRSA. Different institutions have varying practices surrounding inclusion of non-MRSA infections in AUC protocols. Depending on the organism, consider using an alternative agent (e.g. daptomycin for Enterococcus spp.) or continuing to use trough goals of 10 – 18 (vs 10-15).
Why is AUC-based monitoring not recommended in patients with unstable renal function?
With rapid renal function changes comes changes in the patient's total vancomycin exposure. Drawing two levels in these patients is somewhat wasteful since the levels would need to be constantly redrawn. In this setting, consider using a trough goal (12 – 18) and convert to AUC-based monitoring once renal function has stabilized.
Is there an appreciable decrease in vancomycin-associated acute kidney injury (AKI) when using AUC-based dosing?
Yes, several institutions have demonstrated a sustained decrease in vancomycin AKI after switching to AUC-based dosing. For example, see Finch N et al. Antimicrob Agents Chemother. 2017;61(12)e01293-17.
For vancomycin dosing in obese patients, what weight should be used in dosing calculations, and what is the relationship between body weight and volume of distribution?
Total body weight should be used to dose vancomycin. Volume of distribution does increase with actual body weight; however, this pharmacokinetic parameter does not increase proportionally with body weight and is therefore not reliably predictable in obese individuals.
Can you use AUC-based vancomycin dosing when the MIC = 2?
First, verify that the MIC is actually 2 mg/L. The method of determining the MIC may impact the result (see Kruzel et al. J Clin Microbiol.2011;49(6)2272-3). Second, and most importantly, evaluate the patient's clinical status. If the patient is responding to therapy and the total daily dose is less than 4 grams per day, then proceed with caution or consider an alternative agent (See section on vancomycin failures Liu et al. Clin Infect Dis. 2011;51(3)e18-55)
Why would you not just aim for a maximum trough concentration of 15 vs switching to AUC-based dosing?
While most of the time patients can achieve an AUC of 400-600 with a corresponding trough of 12-15, it is not guaranteed. Some patients may require troughs >15 to reach the AUC target. There are some modeling data that suggest that ~60% of patients need a trough of <15 to get to AUC goal. However, that leaves a significant group of patients that would not fall into the 12-15 category. Additionally, trough monitoring is more likely to be associated with vancomycin induced acute kidney injury than AUC monitoring.
What if a patient's AUC is within the goal range of 400-600, but their trough is less than 10?
If the patient is stable, and an AUC target of 400-600 has been achieved with a trough <10, consider continuing with AUC-based monitoring and not increasing exposure to achieve a trough >10. If the patient is unstable/worsening clinically, and all other medical issues have been addressed (i.e., adequate source control …etc.), then you may consider increasing the AUC target (not to exceed 600), which will cause the trough concentration to increase as well. Alternatively, change therapy to an alternative MRSA agent, as recommended by the IDSA MRSA guidelines (Liu et al. Clin Infect Dis. 2011;51(3)e18-55).
NEW! Is it appropriate to use one level to estimate a vancomycin AUC without a Bayesian calculator?
If a Bayesian calculator is not being used, 2 concentrations should be obtained to calculate the vancomycin AUC. As described in 2020 ASHP guidelines, "the AUC is the integrated quantity of cumulative drug exposure (ie, the serum drug concentration–time curve over a defined interval). In contrast, the trough represents a single exposure point at the end of the dosing interval. For troughs of 15 to 20 mg/L, this typically equates to a daily AUC in excess of 400 mg·h/L. However, there is considerable variability in the upper range of AUC values associated with a given trough value."
NEW! When is the most appropriate time to draw the 2 concentrations for an AUC calculation?
The first concentration should be a post-distributional level, collected at least 2 hours after the end of the vancomycin infusion. The second concentration is ideally timed as a true trough. To ensure an accurate estimation of the ke the two concentrations should be drawn as far apart as possible while avoiding the distribution phase at the end of the infusion.
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