AAP recommends optimal treatment for early-onset bacterial sepsis in preterm infants

Samir S. Shah, MD, MSCE

“Suspected sepsis” is a diagnosis commonly assigned to newborn infants, particularly those requiring admission to the neonatal intensive care unit within the first few days of life. While the incidence of early-onset neonatal sepsis (sepsis occurring within the first 3 days of life) has declined considerably since the widespread use of intrapartum antibiotic prophylaxis for women colonized with group B Streptococcus (GBS), several important challenges remain.

These challenges are highlighted in the recent AAP clinical report by Polin and colleagues. First, clinical signs of infection in the neonate are non-specific. This means that it is difficult to distinguish neonates with early signs of sepsis from those with non-infectious, and occasionally self-limited, conditions such as transient tachypnea of the newborn.

Second, clinical examination and simple diagnostic tests do not reliably distinguish infected from uninfected infants, leading to frequent empiric treatment of uninfected infants. Third, knowledge of risk factors for early-onset neonatal sepsis, such as maternal group B streptococcus colonization and prolonged rupture of membranes, may raise or lower ones suspicion for sepsis but the positive predictive value of such factors in identifying infected neonates is poor. This means that most high-risk infants will not have invasive bacterial infection.

The clinical report highlights the pathogenesis and epidemiology of early-onset sepsis, reviews diagnostic tests commonly performed in infants with suspected sepsis, and provides guidance on evaluation and treatment of symptomatic and asymptomatic term and preterm infants with risk factors for sepsis.

With regard to blood cultures, the authors reinforce the importance of obtaining at least 1 mL of blood for culture, as this minimum volume will have a substantively higher yield than when smaller volumes are obtained. The authors also emphasize that umbilical vein cultures, when obtained at the time of delivery from an adequately prepared segment of the umbilical cord, serve as appropriate sources of culture material in lieu of a peripheral blood culture.

The authors also acknowledge that the decision to perform a lumbar puncture in a neonate with suspected early-onset sepsis remains controversial. The likelihood of bacterial meningitis in a high-risk but well-appearing neonate is quite low. In contrast, almost one-quarter of infants with bacteremia have bacterial meningitis. Therefore, the authors encourage the performance of lumbar punctures in all infants with early-onset sepsis and positive blood cultures.

A slightly more controversial point, but one with an expanding evidence base, is the role of acute phase reactants such as the C-reactive protein in identifying asymptomatic infants with risk factors for sepsis who have a low probability of infection (ie, those with negative blood cultures and normal C-reactive protein (CRP) and white blood cell count 6 to 12 hours after birth). These infants do not always require empiric (ie, if there was inadequate antepartum prophylaxis) or prolonged (ie, if there was maternal choramnionitis but lab data remain normal over the first 6 to 12 hours of life) antibiotic therapy. The clinical report specifically encourages discontinuation of antibiotic therapy at 48 hours in clinical situations in which the probability of sepsis is low. However, there are insufficient data to recommend following sequential CRP measurements to determine duration of antibiotic therapy in an infant with an initially abnormal CRP value. Procalcitonin appears more sensitive than CRP in identifying neonates with early-onset sepsis, however additional studies are required before procalcitonin values can be used to guide antibiotic therapy in this population.