Early-Onset Sepsis

KEY POINTS

• 1.

  Early-onset sepsis (EOS) is defined by blood and/or cerebrospinal fluid culture-confirmed infection occurring 0 to 6 days after birth.

• 2.

  Incidence is highest among preterm infants, particularly those born with low gestational ages and with birth weight <1500 g.

• 3.

  Pathogenesis commonly involves ascending colonization of the uterine compartment with maternal flora, with subsequent colonization of the fetus and transition to invasive infection in utero or in the hours and days after birth

• 4.

  Risk factors include low gestational age, duration of rupture of membranes, colonization with high-risk organisms such as group B Streptococcus (GBS), and evidence of maternal intraamniotic infection, such as intrapartum maternal fever.

• 5.

  The most common causative organisms are GBS and Escherichia coli .

• 6.

  Newborns with EOS may be well-appearing at birth, but ∼90% have signs of infection within 24 hours after birth.

• 7.

  Ampicillin and gentamicin are currently the recommended choice for empiric antimicrobial therapy. Broader-spectrum therapy should be considered for critically ill newborns at highest risk of EOS, until culture results are known.

Introduction

Early-onset sepsis (EOS) among term infants is a low-incidence but potentially fatal complication of birth. Among preterm, particularly low-gestation, very low birth weight (VLBW, birth weight <1500 g) and extremely low birth weight (ELBW, birth weight <1000 g) infants, EOS is more common and a significant contributor to morbidity and mortality. EOS is defined by isolation of a pathogenic species from blood or cerebrospinal fluid (CSF) culture in the first week after birth. Among continuously hospitalized, primarily preterm infants, EOS diagnosis is limited to infection occurring ≤72 hours after birth. For these infants, risk factors for infection and microbiology of infection both transition away from the perinatal period to reflect nosocomial factors around this time frame. Among term infants, EOS diagnosis is most commonly made at <48 hours after birth; for example, 95% of EOS caused by group B Streptococcus (GBS) occurs at <48 hours of age. Rarely, otherwise healthy infants may be discharged from the birth hospital and develop EOS in the first week after birth. Bacteria are the primary cause of EOS; fungal species are very occasionally isolated. ^,

Epidemiology

The incidence of EOS is inversely related to gestational age at birth. National surveillance conducted by the Centers for Disease Control and Prevention (CDC) demonstrates that overall US national incidence was constant from 2005 to 2014 at 0.7 to 0.8 cases/1000 live births. Among infants born at ≥37 weeks’ gestation, the incidence is approximately 0.5 cases/1000 live births. In contrast, prospective surveillance among centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) from 2015 to 2017 found an incidence of 18.5 cases/1000 live births occurring at 22 to 28 weeks gestation and 6.2/1000 among those born at 29 to 33 weeks’ gestation. This study observed an incidence of 13.9 cases/1000 live birth among VLBW infants.

Pathophysiology

The pathogenesis of EOS begins with invasion of the intraamniotic compartment with bacterial species from maternal sources. The pathologic processes of EOS were described in seminal papers by Benirschke and Blanc, who described the “amniotic infection syndrome” as the cause of congenital bacterial sepsis and pneumonia, contrasting this entity with the transplacental, hematogeneous origin of congenital viral infection. ^, Rarely, pathogenic bacteria infecting the maternal bloodstream may cause EOS via the transplacental route. The classic example is EOS caused by Listeria monocytogenes, a foodborne pathogen with placental tropism that can cause fetal infection via the maternal bloodstream. Most commonly, EOS pathogenesis begins by ascending colonization via the cervix into the uterine compartment with bacteria normally resident in the maternal gastrointestinal and genitourinary colonizing flora. Transition from fetal colonization to invasive infection via membranous surfaces then occurs, either in utero or after birth. Fetal infection may also occur in utero by aspiration of infected amniotic fluid. This pathogenesis primarily proceeds during labor and is promoted by membrane rupture but rarely can occur before the onset of labor.