Comparison of Bayesian-derived and first-order analytic equations for calculation of vancomycin area under the curve

Introduction Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC(24):MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC(24), there are currently no large studies directly comparing these methods. Objective To compare calculated vancomycin AUC(24) using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. Methods This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC(24) was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx (TM) software platform was used to calculate Bayesian AUC(24). Pearson's correlation and clinical agreement (based on AUC(24) classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA). Results Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L). Conclusions Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC(24). As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC(24).