Tamara van Donge

Key components for antibiotic dose optimization 53 3 After model development and validation it is essential to communicate the strengths and applicability of the model to the users (mostly physicians). Understandable decision support tools, which do not ensure additional time-consuming activities during routine practice, would be valuable. 28,46 An example of these software tools is the model-supported therapeutic drug monitoring tool for precision dosing TDMx (http://www.tdmx.eu/) . Since there are several population PK models published for antimicrobial agents, researchers should assess new data or use existing data to extend and improve existing population PK models. 28,57 Pharmacometric PK/PD models can help identify the optimal (efficacious and safe) therapeutic window necessary to successfully treat an infection. 58 Conclusion There are still numerous challenges to overcome the burden of sepsis in neonates and infants, of which the lack of implementation of optimized dosing recommendations can be considered as remarkably important. Key components for the optimal antibiotic treatment of sepsis in neonates and infants are indicated as treatment phase, dose, drug exposure and response. A conceptual distinction can be made between the empirical and targeted treatment phase. During the first days of treatment the focus lies on establishing an efficacious dose, thereafter the balance is shifting towards ensuring a safe and nontoxic treatment. In the pediatric population, the exposure of treatment is affected by developmental changes such as maturation of organ function and metabolizing enzymes, which requires dosing adjustments. The response or treatment effect can be determined by the microbiological parameters (MIC) together with the pathogen characteristics (time- or concentration dependent). Understanding these components and their underlying relationship might provide a basis for proper antibiotic use and reduction of antibiotic resistance. This also illustrates the necessity of a close multidisciplinary collaboration between physicians, pharmacists, pharmacometricians and microbiologists to assure optimal antibiotic use in neonates and infants.