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Is trough-based vancomycin dosing achieving therapeutic targets?

  • At: PPR SIG 2021 (2021)
  • Type: Digital
  • By: WONG, Sherilyn (University of South Australia, Australia)
  • Co-author(s): Sherilyn Wong, Wen Huey Chong, Stephanie E Reuter
  • Abstract:

    Introduction

    Therapeutic drug monitoring (TDM) of the antimicrobial drug, vancomycin, is recommended due to its high variability between patients in order to minimise toxicity and maximise efficacy. A daily area-under-the-curve (AUC24) target of 400-650 mg.hr/L (assuming a MIC of 1mg/L) is the recommended therapeutic target. A large number of Australian hospitals use trough concentrations for dose adjustment, however it is unknown how well trough-based guidelines perform in achieving this therapeutic target.

    Objectives

    To evaluate the ability of trough-based vancomycin dosing regimens to meet established therapeutic targets.

    Methods

    A review of current vancomycin dosing guidelines was conducted. A population pharmacokinetic approach was then used to evaluate the ability of dosing guidelines to meet therapeutic targets (AUC24 400-650mg.hr/L). A representative population of 1000 patients was constructed and, using a previously published model, various dosing regimens were simulated. The proportions of patients who achieved sub-therapeutic, therapeutic and toxic vancomycin exposure over a treatment course were calculated.

    Results

    Guidelines of four major teaching hospitals within Australia and the Australian Therapeutic Guidelines were identified. The majority of guidelines were predicted to result in at least 75% of patients to be at therapeutic AUC within the first 48 hours. Following TDM-based dose adjustment using trough concentrations, at least 50% of patients were predicted to be in the toxic range, a proportion which increased over the remainder of the treatment course.

    Conclusion

    This work supports evidence of the limitations of trough-based dosing for vancomycin TDM and indicates that current dosing regimens are sub-optimal. Further work is required to implement AUC-based dosing strategies into practice. This study also demonstrates the application of population pharmacokinetics in optimising individualised dosing in patients.

Last update 4 October 2019

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