New sepsis guidance addresses epidemiology, microbiology, recommended empiric treatment
Karen M.Puopolo, M.D., Ph.D., FAAP
AAP Clinical Report
Neonatal clinicians have updated the guidance for evaluating newborns for risk of
early-onset bacterial infection. The AAP guidance distinguishes infants by gestational
age at birth and provides new evidence-based management options.
As the national incidence of neonatal early-onset sepsis (EOS) has declined over the
past 30 years, this infection presents neonatal caregivers with a difficult clinical
problem: an infection with low incidence, high consequence and nonspecific clinical
manifestations that can be indistinguishable from normal newborn transition or conditions
of prematurity. Faced with this situation, it is no surprise that newborns frequently
are administered empiric antibiotics for risk of EOS.
The intent of such practice is to keep newborns safe. However, the unintended consequences
of empiric antibiotic administration to uninfected newborns may manifest as increased
risks of death, necrotizing enterocolitis and chronic lung disease among very preterm
infants, as well as negative impacts on exclusive breastfeeding and increased risks
of early childhood atopic diseases. The mechanisms through which early antibiotic
exposures may influence later health outcomes remain incompletely defined, but these
observations mean that clinicians must carefully weigh the risks and benefits of empiric
antibiotic use in the newborn period.
Separate reports reflect differences
The AAP Committee on Fetus and Newborn and the Committee on Infectious Diseases revised
the AAP guidance on early-onset bacterial infection in the clinical reports Management of Neonates Born at ≥35 0/7 Weeks’ Gestation With Suspected or Proven Early-Onset
Bacterial Sepsisand Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset
Bacterial Sepsis. The reports are available at https://doi.org/10.1542/peds.2018-2894 and https://doi.org/10.1542/peds.2018-2896 and will be published in the December issue of Pediatrics.
In deciding to issue separate reports, the committees acknowledged data published
since the last revision have highlighted the differences in EOS epidemiology, microbiology,
clinical risk factors and clinical management algorithms that distinguish term and
The reports update the current epidemiology, microbiology and recommended empiric
treatment of EOS. A number of issues that present difficulties to the neonatal clinician
are addressed, including the use of laboratory tests to assess risk of EOS, the optimal
approach to blood culture and uncertainties in the obstetrical diagnosis of intra-amniotic
infection (formerly and commonly referred to as chorioamnionitis). In addition, the
reports provide some guidance on the principles of antimicrobial stewardship as they
apply to EOS management. Most notably, they offer updated guidance on EOS risk assessment.
Highlights of the reports include the following:
Infants born at ≥35 0/7 weeks’ gestation can be stratified by level of risk for EOS
using one of these approaches:
categorical algorithms using threshold values for intrapartum sepsis risk factors;
serial physical examination to detect the presence of clinical signs of illness. This
approach may begin with categorical or multivariate risk assessment or may be applied
to all newborns.
Infants born at ≤34 6/7 weeks’ gestation can be categorized by level of risk for EOS
by the circumstances of their preterm birth:
Infants born preterm by cesarean section because of maternal noninfectious illness
or placental insufficiency in the absence of labor, attempts to induce labor or membrane
rupture before delivery are associated with a relatively low risk of EOS. In these
cases, physicians should consider the risk/benefit balance of EOS evaluation and empiric
Infants born preterm because of maternal cervical incompetence, preterm labor, premature
rupture of membranes, clinical concern for intra-amniotic infection or acute onset
of unexplained non-reassuring fetal status are at the highest risk of EOS. Such neonates
should undergo EOS evaluation with blood culture and empiric antibiotic treatment.
Birth centers should consider the development of local guidelines for EOS risk assessment
and clinical management based on gestational age category and monitor guideline outcomes.
For all infants, regardless of gestational age: When blood cultures are sterile, antibiotic
therapy should be discontinued by 36-48 hours of incubation, unless there is clear
evidence of site-specific infection.
Dr. Puopolo is lead author of the clinical reports and a member of the AAP Committee
on Fetus and Newborn.