Sanne Hoeks

General Discussion 113 7 CLINICAL IMPLICATIONS IN NEONATAL CARE Antibiotics in early life: lifesaving or devastating? Current clinical practice comprises that antibiotic treatment is initiated in neonates directly after birth based on a risk assessment for early onset neonatal sepsis (EONS) that is composed of maternal factors and clinical symptoms. The results of the blood culture, the golden standard to diagnose sepsis, are awaited for at least 36 hours. Prevalence of a culture proven EONS is 0.1%, antibiotic treatment is initiated in 4-7% of the newborns, 63-66 which indicates a huge overtreatment. On top of that, multiple (clinical) reasons to continue antibiotic treatment despite a negative blood culture are reported and it is not unusual in the neonatal ward to continue treatment for (a random) seven days. 67 However, neonatal sepsis often presents with aspecific symptoms and can progress extremely fast if not treated immediately. The molecular adaptations of immune cells described in chapter 2 and 3 underscore that immune regulating mechanisms are importantly programmed into immune cells in this phase of life. Strategies to boost the immune system of newborns have failed and future research is in need of a systems immunology approach in contrast to a stand-alone immune modulator like some specific cytokine. Focus of future research should aim for better diagnostic tools like the clinical use of early markers for sepsis. At present, sufficiently robust decision tools to disentangle (sensitivity versus specificity) infectious events from other commonly observed events in neonates are still lacking. 68 Neonatal care is highly in need of new methods to diagnose sepsis accurately, discriminative and fast. Not only to treat patients for potential life threatening sepsis but also to prevent newborns from unnecessary and also potential harmful exposure to antimicrobial therapies. 69-71 New diagnostic approaches for early identification of patients suffering from infection together with the identification of the causative microbes, are therefore urgently needed to reduce the incidence and mortality of neonatal sepsis. Two new promising tools are: Procalcitonin (PCT) as a negative predictor for sepsis and Next Generation Sequencing (NGS) to identify pathogens during sepsis.