Tamara van Donge

Abstract Sepsis in neonates and infants remains a major cause of death despite a decline in child mortality and morbidity over the last decades. Developmental changes such as maturation of organ function and capacity of metabolizing enzymes can affect drug exposure and response in neonates and infants. Optimal treatment of sepsis in neonates and young infants is dependent on several key components such as treatment phase, dose, drug exposure and response. During the initial phase of suspected sepsis, the primary focus of empirical treatment is to assure efficacy. Once sepsis is confirmed this focus shifts towards a targeted treatment ensuring an optimal balance between efficacy and safety. Clinical response to antibiotic treatment in neonates and infants does not depend only on dose and drug exposure but also on the pathogen and its characteristics, together with the characteristics of the patient population such as reduced humoral response or reduced skin barrier function. In order to overcome the burden of sepsis new and quick diagnostic tools (biomarkers), adequate descriptors for drug at the target site, and time-varying killing activity parameters (kill-curves) are necessary together with close multidisciplinary collaborations to assure optimal antibiotic use in neonates and infants. Understanding such key components and their underlying relationships can provide a scientific basis for optimal and individualized utilization of antibiotic agents. Keywords: sepsis, neonates, infants, empirical phase, targeted phase, antibiotics, dose, drug exposure, response