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

Abstract

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. To compare calculated vancomycin AUC24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. 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 72h 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). 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=-11.5mg*h/L) and -92 to 113 (MD=-10.4mg*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=-21.9mg*h/L). 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 .