Vancomycin area under the curves estimated with pharmacokinetic equations using trough-only data

What is known and objective The revised vancomycin monitoring guidelines recommend targeting an area under the curve (AUC) of 400-600 mg*hr/L for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. An AUC can be measured by checking a peak and trough concentration at steady state; however, this requires obtaining an additional blood sample. The most practical way to perform AUC-guided dosing is by estimating an AUC from a steady-state trough. The purpose of this study was to compare AUCs estimated from trough-only data to AUCs calculated from peak and trough concentrations. Methods Steady-state peak and trough data were collected from an open-access clinical calculator VancoPK.com. Patients were included who had (1) peaks drawn >= 60 min after the end of infusion, (2) peak and trough levels drawn >= 4 h apart and (3) troughs drawn <= 4 h early or late. The population was randomized and divided into a model group and test group. A population equation for vancomycin volume of distribution (Vd) was derived and compared to other general adult Vd models. Accuracy and precision of estimated AUCs were measured with bias, root mean square error (RMSE) and Lin's concordance correlation. Results and discussion A total of 2,500 adult patients were included in the model group and 1,843 were included in the test group. The derived Vd equation, Vd (L) = 0.29(age) +0.33(total BW in kg) +11, produced accurate and precise AUC estimates from trough-only data. The mean actual AUC and estimated AUC were 504 and 503, respectively, with a correlation of 0.926. The RMSE between estimated and actual AUCs was 47.7, meaning that over 95% of estimated AUCs were within 100 points of actual AUCs with the study's Vd model. Other Vd models performed well for certain types of patients, depending on their body weight and age. What is new and conclusion There is limited evidence from large, robust populations regarding how to estimate Vd for general adult patients. Accuracy and precision of estimated AUCs depend on the applied population Vd model. The Vd model from the present study can be used for AUC-guided dosing with trough-only data which requires less blood work than peak-trough monitoring. AUC calculations are practical with the use of open-access websites.