Sanne Hoeks

Chapter 7 114 Procalcitonin (PCT) PCT is an inflammatory marker that can be used to exclude sepsis. 72 A large randomized control trial showed that serial low PCT values make it possible to safely stop antibiotic treatment in newborns within 24 hours after birth (NeoPInS). Furthermore, serial PCT measurements are able to guide doctors daily in the questionable need for antibiotic therapy in an individual patient (NeoPInS). Antibiotic therapy will not only address micro-organisms in blood, it will also affect the microbiota. To prevent long term consequences by disrupting the proper formation of the microbiome and subsequently disrupting the programmed development of the immune system, unnecessary antibiotic treatment must especially be avoided in this age group. Therefore, PCT is now implemented in clinical guidelines to prevent and treat neonatal early onset sepsis. A limitation of PCT guided therapy is that it is only applicable for infants with a medium or low risk for early onset sepsis (EONS), high risk infants are often treated with antibiotics for long time despite a negative bloodculture. To reduce duration of antibiotic treatment is one thing, not to start antibiotics and to exclude sepsis would be the best. PCT has also been shown as a promising marker to rule out sepsis in cord blood. 73, 74 The limitation of early PCT measurement is that it does not allow the detection of late infections due to vertical transmission, furthermore, it has not been tested in late-onset neonatal sepsis. These limitations request an innovative technique that would be able to identify sepsis fast, reliable and is discriminative for different pathogens like bacteria, viruses and fungi. Next Generation Sequencing It has been shown in adults that circulating cell-free DNA (cfDNA) from blood plasma of adult septic patients is a more sensitive and specific analyte to identify pathogens by NGS compared to the traditional golden standard, the blood culture. This technique is not new, however a bioinformatics workflow coupled with statistical tests now reveals the clinical relevance. 75 NGS-based diagnosis offers many advantages: First, it is an open platform, providing the opportunity to detect bacterial, fungal and viral pathogens in a single assay. Second, it is quantitative by counting sequence reads and calculating statistical significances. It can therefore potentially discriminate between unspecific colonization, contamination or infection. Third, this technique might in the future be applied at bedsite. The clinical applicability of NGS is currently investigated in late onset neonatal sepsis as LOS is associated with higher chance to find a causative agent in the bloodculture and therefore LOS is a better model to evaluate the clinical use of this technique than EONS.