The relationship of vancomycin 24-hour AUC and trough concentration

Abstract

Purpose: Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 μg/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 μg · h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software. The aim of this investigation was to determine the relationship between AUC and trough concentration and the influence of dosing regimen on goal achievement. Methods: The relationship between trough concentration and AUC was explored through derivation of an equation based on a 1-compartment model and simulations. Results: 24-hour AUC is related to dosing interval divided by half-life in a nonlinear fashion. The target trough concentration can be individualized to achieve a desired AUC range, and limiting use of large doses (>15-20 mg/kg) can protect against excessive 24-hour AUC with trough-only monitoring. Conclusion: After initially determining pharmacokinetic parameters, subsequent monitoring of AUC can be accomplished using trough concentrations only. Trough concentration may be used as a surrogate for AUC, although the acceptable target trough concentration will vary depending on dosing interval and elimination rate constant. This work included development of an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.