Project summary in plain language

Individualisation of Antibiotic Therapy in Intensive Care Patients Using Dosing Software Tools

Individualization of antibiotic therapy by evaluating software tools for model-based precision dosing of Piperacillin and Meropenem in critically ill patients

Problem/patient group

In critically ill patients, target attainment of blood levels of antibiotics like piperacillin and meropenem is often low due to organ impairments, organ support and disease-related changes in body functions, when using standard dosing [1]. While regular measurements of concentrations help control and guide therapy regimens, they do not support initial dosing or provide clear recommendations for dose adaptions in case of non-target attainment. A next step towards personalised antibiotic therapy is the development of dosing software tools that model antibiotic concentrations considering individual patient factors and calculate appropriate dosages [2]. Available dosing software tools differ in their methodological approach, functionality and design – and thus also in their appropriateness for clinical use [3].

Aim

My project aims to compare dosing software tools for piperacillin and meropenem in critically ill patients, focussing on their accuracy of predicted concentrations, calculated dose recommendations and user friendliness.

Implementation

After identifying suitable dosing software tools, their predicted concentrations will be compared with measured concentrations to assess their accuracy. For that, data from multiple clinical trials from different hospitals will be used (number of measurements/patients: piperacillin 3654/561; meropenem 3924/486). The most promising tools will be compared regarding clinically relevant differences in dose recommendations. Finally, a usability study will be conducted.

Result

In the systematic search, 120 dosing software tools were identified and assessed for eligibility. Currently, eleven tools are included and accessible. An interim analysis showed that at least 22 different piperacillin and 19 meropenem models are implemented in these tools.

Patient benefit

The use of dosing software tools for precision dosing of piperacillin and meropenem aims to increase target attainment of intensive care patients – and thereby decrease the risk for therapy failure, antibiotic resistance and toxicity [1]. My project supports the rational selection of such tools to ease their integration into clinical routine.

 

Figure 1: Stepwise Evaluation Process of Dosing Software Tools for Piperacillin and Meropenem in Critically Ill Patients

Image source: Sabrina Böing

 

[1] Brinkmann A, Chiriac U, Grabein B, Liebchen U, Hagel S, Kunzelmann AK, et al. Antibiotikatherapie bei kritisch Kranken auf der Intensivstation – was sollten wir beachten und nicht aus dem Fokus verlieren? Anästh Intensivmed 2024;65:52–64. https://doi.org/10.19224/ai2024.052.
[2] Minichmayr IK, Dreesen E, Centanni M, Wang Z, Hoffert Y, Friberg LE, et al. Model-informed precision dosing: State of the art and future perspectives. Advanced Drug Delivery Reviews 2024:115421. https://doi.org/10.1016/j.addr.2024.115421.
[3] Kantasiripitak W, Van Daele R, Gijsen M, Ferrante M, Spriet I, Dreesen E. Software Tools for Model-Informed Precision Dosing: How Well Do They Satisfy the Needs? Front Pharmacol 2020;11:620. https://doi.org/10.3389/fphar.2020.00620.