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 (AUC₂₄: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 AUC₂₄, there are currently no large studies directly comparing these methods. Objective: To compare calculated vancomycin AUC₂₄ 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. AUC₂₄ was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC₂₄. Pearson's correlation and clinical agreement (based on AUC₂₄ 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 AUC₂₄. 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 AUC₂₄.