Neonatal sepsis should always be considered in any sick newborn presenting with symptoms of respiratory distress, hypotension, electrolyte disturbance, poor feeding, or lethargy Neonatal sepsis often presents with hypothermia Neonates may not react to an infection with fever Avoid ceftriaxone due to its ability to displace bilirubin and aggravate hyperbilirubinemia Neonates with a suspected UTI should have a full sepsis workup and be admitted for intravenous antibiotic therapy Direct hyperbilirubinemia or new onset of jaundice after days of life is suspicious for a neonatal UTI Current Evidence Concern for neonatal sepsis is one of the most commonly encountered clinical situations for newborns in the ED General incidence of sepsis in neonates is approximately 0.98 per 1,000 live births It can be categorized into early onset (occurring in newborns who are less than 72 hours of life) or late onset (occurring between and days of life) Early-onset disease occurs through perinatal or vertical transmission from the mother Early-onset disease is caused by microbial flora present in the vaginal tract (GBS, E coli or other gram-negative bacilli, Staphylococcus aureus, Enterococci, viridans group Streptococci, Group A Streptococci, syphilis, H influenzae , Listeria monocytogenes ) Risk factors for early-onset disease usually relate to perinatal exposures (prolonged rupture of membranes, chorioamnionitis, GBS-colonized mother with inadequate intrapartum antibiotics) Late-onset disease may occur through horizontal transmission from the infant’s environment or caregivers and is caused by environmental flora (Staphylococci, E coli, GBS, and candidiasis) Although more commonly seen in the NICU, risk factors for late-onset disease include prematurity, presence of congenital heart disease, gut pathology, and presence of central catheters Other pathogens causing sepsis include viral (herpes simplex, enterovirus, cytomegalovirus, adenoviruses), fungal (systemic candidiasis), and atypical bacteria (Toxoplasma) agents Neonatal infection induces a systemic inflammatory response which accounts for much of the capillary leak and inflammation associated with the disease