Model-based individualisation of piperacillin therapy in critically ill patients

• Applicant: Dr. Uwe Liebchen
• Subject Area: Medical Informatics and Medical Bioinformatics ; Anaesthesiology ; Pharmacy
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504995322

The mortality of sepsis and septic shock is persistently high. Timely antibiotic therapy plays a key role in the treatment and is regularly the only causal therapeutic option. The selection of the appropriate drug and dosage is imperative for a successful therapy. However, during the last few years, there have been numerous reports that the administration of antibiotics in standard doses led to inadequate concentrations, so that individualized dosing approaches are urgently needed. Hypothesis: Individualization of antibiotic therapy in critically ill patients will lead to improved outcome and avoidance of resistance in severe infections. Individualization of piperacillin therapy is possible through model-based dosing. Objectives: 1. To systematically evaluate pharmacokinetic piperacillin models based on a multicenter dataset and to identify the most applicable one. 2. At the same time, a meta-model based on the multicenter dataset will be built and compared with existing (monocentric) models. 3. The model with the best predictive properties will be used for the following applications: a. Development of a rational dosing algorithm based on the specific resistance situation of Pseudomonas aeruginosa in intensive care patients including determination of the optimal "loading dose" before continuous infusion. b. Use in the context of Bayesian Forecasting c. Development of an online application to adapt the dosing algorithm to centre-specific resistance patterns d. Implementation of the results in the online software "tdmx.eu". Expected results: The results of the project offer the possibility for a reliable, individualized, and rational piperacillin therapy in intensive care patients. The development of an online tool and the implementation in a freely available software make the results usable in everyday clinical practice.

• DFG Programme: Research Grants