Neonatal sepsis biomarkers: where are we now?

Abstract

Neonatal sepsis is still the major cause of mortality and morbidity in newborn infants. The incidence varies between 1 - 4 newborns/1000 live births/year. Up to 25 % of the affected newborns may develop meningitis, and case fatality ranges between 5 - 60 %. It has been estimated that up to 1.6 Million newborns per year may die worldwide as a consequence of neonatal sepsis. In Western countries early-onset sepsis is mainly caused by group B streptococci (GBS) and Escherichia coli whereas Klebsiella- and Pseudomonas species are the predominant microorganisms in developing countries. Premature rupture of membranes clearly increases the risk for neonatal bacterial infections, and some observational studies indicate that the risk has already begun to rise 12 hours after membranes have ruptured. Approximately 1 % of neonates colonized with GBS will eventually develop severe early onset sepsis; the majority of infections present within 24 hours of life. In very immature preterm infants the risk for early-onset infections and case fatality rate are significantly higher when compared with term newborns. Up to 60 % of very immature infants may have been exposed to chorioamnionitis, and a high proportion of them may be born with inflamed lungs and signs of a fetal inflammatory response syndrome (FIRS). A number of investigators have convincingly shown that FIRS is associated with an increased risk for severe pulmonary and cerebral morbidity. In the group of very low birth weight infants (VLBW) the incidence of nosocomial sepsis is alarmingly high. Up to 40 % of these babies may develop systemic infections predominantly caused by coagulase negative staphylococci. Well defined risk factors of nosocomial sepsis are mechanical ventilation, central catheters, i.v.-lipids and late enteral feeding. In addition, staff hands, insufficient hand washing practices and an overcrowded NICU have been shown to contribute significantly to the transmission of pathogens. Meticulous attention to handwashing with regular monitoring and surveillance of handwashing practice and reporting of compliance is mandatory. Especially very immature preterm infants suffer from a considerable number of partial immunodeficiencies which predispose these babies at risk for microbial infections. However, neither prophylactic nor therapeutic application of i.v. immunoglobulins was shown to improve outcome of this high risk population. Similarly, substitution of colony stimulating factors for granulocytes and macrophages failed to reduce mortality and the incidence of sepsis. Nevertheless, a number of better practices may help to reduce the incidence of nosocomial infections: strict adherence to hygiene protocols, reduction of invasive procedures associated with neonatal intensive care, early enteral feeding with breast milk, rational strategy for antibiotic treatment and others. In addition, a detailed antenatal history, a careful physical examination and, subsequently, a regular and sensitive clinical monitoring of neonates at risk will help to identify early signs of infection and to initiate a timely therapy.