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Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study

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Abstract

Background

The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic–pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15–25 mg/L.

Aim

To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions.

Method

A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data.

Results

Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613 mg.h/L with CSS 25 mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0–24/MIC values. Retrospective Bayesian modelling demonstrated on median 250 mg/24 h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405–460) mg.h/L and CSS 18.8 (range 16.8–20.4) mg/L.

Conclusion

Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

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Funding

No specific funding was received.

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Authors and Affiliations

  1. The Royal Brisbane and Women’s Hospital, Herston, Australia

    J. Nolan, K. McCarthy & M. L. Avent

  2. School of Medicine, University of Queensland, 4029, Herston, Australia

    J. Nolan & K. McCarthy

  3. Mount Sinai West Hospital, New York, USA

    A. Farkas

  4. Optimum Dosing Strategies, Bloomingdale, New York, USA

    A. Farkas

  5. Queensland Statewide Antimicrobial Stewardship Program, University of Queensland Centre for Clinical Research, Herston, Australia

    M. L. Avent

Authors
  1. J. Nolan
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  2. K. McCarthy
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  4. M. L. Avent
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Corresponding author

Correspondence to J. Nolan.

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Conflicts of interest

A.F. is the developer of the Individually Designed Optimum Dosing Strategy (ID-ODS http://www.optimum-dosingstrategies.org/) which was the program utilised in this work.

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Nolan, J., McCarthy, K., Farkas, A. et al. Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study. Int J Clin Pharm 45, 1444–1451 (2023). https://doi.org/10.1007/s11096-023-01618-5

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  • DOI: https://doi.org/10.1007/s11096-023-01618-5

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