Examining the relationship between vancomycin area under the concentration time curve and serum trough levels in adults with presumed or documented staphylococcal infections
Clark L, Skrupky LP, Servais R, Brummitt CF, Dilworth TJ. Examining the relationship between vancomycin area under the concentration time curve and serum trough levels in adults with presumed or documented staphylococcal infections. Ther Drug Monit. 2019; 41(4):483-488. doi: 10.1097/FTD.0000000000000622.
BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using two-level pharmacokinetic monitoring in order to inform changes to an institutional vancomycin dosing protocol.
METHODS: This was a retrospective observational study performed in two acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to MIC ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected.
RESULTS: Thirty-four patients were included in the study, with two patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%) and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± standard deviation vancomycin Cmin was 16.6 ± 6.1mg/L and the mean AUC/MIC was 588 ± 156mg/L*hr. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n=31/34). Of the patients with a Cmin > 9mg/L, 100%(n=33) achieved AUC /MICvalues >400mg/L*hr and 93.9% were > 500mg/L*hr. There was a strong correlation between vancomycin Cmin and AUC24hr (R=0.731; p<0.001).
CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.