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Background <p>Optimal dosing of vancomycin in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to high pharmacokinetic variability. We aimed to develop individualised vancomycin dosing recommendations that optimise efficacy while minimising toxicity.</p> Methods <p>Prospective, international, pharmacokinetic study enrolling critically ill patients treated with vancomycin and various RRT modalities. A population pharmacokinetic model was developed, externally validated and applied to perform Monte Carlo dosing simulations. We calculated the probability of each dosing regimen to achieve the efficacy target against methicillin-resistant <i>Staphylococcus aureus</i> (ratio of the area under the concentration–time curve to the minimum inhibitory concentration (AUC<sub>0-24&#xa0;h</sub>/MIC) ≥ 400) without exceeding the toxicity threshold (AUC<sub>0-24&#xa0;h</sub> ≥ 700&#xa0;mg.h/L).</p> Results <p>We enrolled 65 critically ill patients from 6 countries receiving continuous RRT (50.8%) or sustained low-efficiency dialysis (49.2%). The model was developed using 1318 pre- and post-filter plasma and effluent concentrations and validated with a new dataset (19 critically ill patients, 124 pre-filter plasma concentrations), with 47.4% patients concomitantly treated with extracorporeal membrane oxygenation. Predictive performance was high (median prediction error =—13.4%). Simulations showed that dosing requirements were dependent on actual body weight and RRT intensity and duration (p &lt; 0.05). An optimised dosing nomogram was subsequently developed considering these clinical characteristics.</p> Conclusions <p>Actual body weight and RRT intensity and duration are the main determinants of vancomycin dosing requirements in critically ill patients treated with RRT. Efficacious, non-toxic dosing may be guided by the optimised nomogram. </p>

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Vancomycin optimised dosing regimens for critically ill patients receiving renal replacement therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Marta Ulldemolins,
  • Jeffrey Lipman,
  • Xin Liu,
  • Mohd-Hafiz Abdul-Aziz,
  • João P. Baptista,
  • Irma Bilgrami,
  • Laurent Bitker,
  • Clement Boidin,
  • Alexander Brinkmann,
  • Vesa Cheng,
  • Gordon Choi,
  • C. Louise Cole,
  • Jan J. De Waele,
  • Renae Deans,
  • Glenn M. Eastwood,
  • Leslie Escobar,
  • Otto R. Frey,
  • Romain Garreau,
  • Sylvain Goutelle,
  • Rebecca Gresham,
  • Maria Patricia Hernandez-Mitre,
  • Janattul Ain Jamal,
  • Gavin M. Joynt,
  • Salmaan Kanji,
  • Jan T. Kielstein,
  • Stefan Kluge,
  • Christina König,
  • Vasilios P. Koulouras,
  • Melissa Lassig-Smith,
  • Pierre-Francois Laterre,
  • Anna Lee,
  • Jean-Yves Lefrant,
  • Katie Lei,
  • Patricia Leung,
  • Mohd-Basri Mat-Nor,
  • Yugan Mudaliar,
  • Marlies Ostermann,
  • Sanjoy K. Paul,
  • Sandra L. Peake,
  • Jordi Rello,
  • Jean-Christophe Richard,
  • Brent Richards,
  • Darren M. Roberts,
  • Michael S. Roberts,
  • Anka C. Roehr,
  • Claire Roger,
  • Leonardo Seoane,
  • Kiran Shekar,
  • Mahipal Sinnollareddy,
  • Eduardo Sousa,
  • Anna Spring,
  • Therese Starr,
  • Dianne Stephens,
  • Fabio Silvio Taccone,
  • Jane Thomas,
  • John Turnidge,
  • Miia Valkonen,
  • Steven C. Wallis,
  • Tricia Williams,
  • Xavier Wittebole,
  • Daniel F. B. Wright,
  • Xanthi T. Zikou,
  • Jason A. Roberts,
  • Max Andresen,
  • Sónia F. Baltazar,
  • Saber Barbar,
  • Eulália Costa,
  • Dominique Durand,
  • Ricardo Freitas,
  • Yarmarly Guerra Valero,
  • Margaret Haughton,
  • Andreas Koeberer,
  • Marin Kollef,
  • Kerenaftali Klein,
  • Ravindra Mehta,
  • Cathy McKenzie,
  • Laurent Muller,
  • Priya Nair,
  • Vineet Nayyar,
  • Jenny L. Ordóñez Mejia,
  • Georgia-Laura Panagou,
  • Jody Paxton,
  • Leah Peck,
  • Mayukh Samanta,
  • Jean-Louis Vincent,
  • Ruth Wan,
  • Helen Young

摘要

Background

Optimal dosing of vancomycin in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to high pharmacokinetic variability. We aimed to develop individualised vancomycin dosing recommendations that optimise efficacy while minimising toxicity.

Methods

Prospective, international, pharmacokinetic study enrolling critically ill patients treated with vancomycin and various RRT modalities. A population pharmacokinetic model was developed, externally validated and applied to perform Monte Carlo dosing simulations. We calculated the probability of each dosing regimen to achieve the efficacy target against methicillin-resistant Staphylococcus aureus (ratio of the area under the concentration–time curve to the minimum inhibitory concentration (AUC0-24 h/MIC) ≥ 400) without exceeding the toxicity threshold (AUC0-24 h ≥ 700 mg.h/L).

Results

We enrolled 65 critically ill patients from 6 countries receiving continuous RRT (50.8%) or sustained low-efficiency dialysis (49.2%). The model was developed using 1318 pre- and post-filter plasma and effluent concentrations and validated with a new dataset (19 critically ill patients, 124 pre-filter plasma concentrations), with 47.4% patients concomitantly treated with extracorporeal membrane oxygenation. Predictive performance was high (median prediction error =—13.4%). Simulations showed that dosing requirements were dependent on actual body weight and RRT intensity and duration (p < 0.05). An optimised dosing nomogram was subsequently developed considering these clinical characteristics.

Conclusions

Actual body weight and RRT intensity and duration are the main determinants of vancomycin dosing requirements in critically ill patients treated with RRT. Efficacious, non-toxic dosing may be guided by the optimised nomogram.