1329 - Vancomycin Therapeutic Drug Monitoring: How to hit the Curve

Background: For the management of serious S. aureus infections, area-under-the curve to minimum inhibitory concentration (AUC/MIC) applied dosing is recommended as the preferred method to goal trough-based monitoring. This pharmacodynamic dosing demonstrates efficacy with optimized exposure and decreased nephrotoxicity. While two levels are ideal for estimating AUC/MIC mathematically, the logistics and costs may outweigh the benefits of this approach. This study will compare AUC/MIC estimates using two single-level pharmacokinetic calculators (C2 and C3) and a Bayesian dosing calculator (C1) versus steady-state troughs.

Methods: A retrospective cohort study using a data repository to identify patients from 2019 included patients on intravenous vancomycin for greater than 48 hours with a steady state trough.  Patients on dialysis or with unstable renal function were excluded. Vancomycin AUC/MIC and peak levels were estimated using C1, C2, and C3. The objective was to assess correlation of trough levels of 10-20mcg/ml to an AUC/MIC of 400-600 mg∙h/L. Secondary outcomes included examining the difference in R-squared values of the three calculators, and the percentage of patients with dose adjustments.

Results: 55 patients met inclusion criteria. Of 55 troughs, 78% were 10-20mcg/ml and 5% were >20mcg/ml. On average, the three calculators found 85% of all initial troughs and 93% of therapeutic troughs correlated to an AUC >400. However, less than half of therapeutic troughs corresponded to an AUC of 400-600 mg∙h/L. Nearly 70% of patients had one or more dose adjustments often for unclear reasons as the AUC/MIC target of 400-600 mg∙h/L was met in 29-63% of initial adjustments. The three different calculators showed noticeable variability in calculating AUC/MIC.Figure 1
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Conclusion: A weak relationship between AUC/MIC and steady state troughs was found. Excess vancomycin exposure was demonstrated in 39% of therapeutic troughs. Over 25% of dose adjustments were deemed unnecessary. Utilizing AUC/MIC estimates for vancomycin may limit excess exposure while reducing the overall number of drug levels. Selecting a single-level calculator is problematic with the high degree of variation between calculators.Figure 4