Late-Onset Sepsis: Epidemiology, Microbiology, and Outcomes Among Very Preterm Infants

Published on in CHOP News

By Dustin D. Flannery, DO, MSCE, Neonatologist

Late-onset sepsis is a significant cause of morbidity and mortality among very preterm infants. Despite substantial infection prevention efforts implemented over the last three decades, and attention paid by local and national public health agencies, as well as insurers, rates of late-onset sepsis remain alarmingly high among very preterm infants, especially those born at the lowest gestational ages (GAs). The epidemiology of late-onset sepsis has changed over time.

We recently completed a prospective observational study to determine the epidemiology, microbiology, and associated outcomes of late-onset sepsis among very preterm infants born between 2018 and 2020 using a large and nationally representative cohort from NICUs across the United States.

Our results—recently published in Pediatrics—have important implications for clinicians who care for very preterm infants at risk for late-onset sepsis, choose empirical antibiotic regimens, and discuss prognostication with families.

Our study included infants born 401 to 1500 g and/or 22 to 29 weeks’ GA from January 1, 2018, to December 31, 2020, at 774 participating Vermont Oxford Network centers from 49 states in the U.S. During the study period, 124,497 eligible infants were admitted to participating NICUs, of which 118,650 infants survived >3 days and were included in the analysis. Overall, 10,501 (8.9%) infants had late-onset sepsis.

Incidence was highest for infants born ≤23 completed weeks’ GA.

Multiple maternal and infant characteristics differed between infected and uninfected infants.

  • Infants with late-onset sepsis were more often born vaginally (33.0% vs. 24.5%), to mothers with chorioamnionitis (17.8% vs. 12.2%) and without hypertension (30.2% vs. 40.3%).
  • Infected infants had lower BWs (760 g vs. 1140 g) and GAs (25 weeks vs. 29 weeks) compared with uninfected infants.
  • Length of stay was longer for infected infants compared with uninfected infants (median 102 days vs. 62 days).

The primary outcome was survival to hospital discharge. Secondary outcomes among survivors included home oxygen, tracheostomy, and gastrostomy or jejunostomy.

We found that very preterm infants with late-onset sepsis had lower overall survival (78.2% vs. 94.9%) and lower survival in each GA category. Those who survived to discharge also had significantly increased adjusted risks for technology-dependent, chronic morbidities upon discharge, including home oxygen, tracheostomy, and gastrostomy, which are associated with significant health burden and resource utilization, including hospital readmissions in the first year after birth.

Remarkably, 34 different pathogens were identified. Coagulase-negative staphylococci (CONS) was the most-common pathogen, but the highly pathogenic Staphylococcus aureus accounted for nearly a quarter of all cases.

Our study results highlight a current challenge in neonatal care. As resuscitation near the limit of viability increases, the imperative to improve late-onset sepsis prevention through a better understanding of pathogenesis is clear: 1 of every 2 infants born ≤23 weeks’ GA in our study who survived past day 3 either died later or suffered late-onset sepsis.

The persistent burden and diverse microbiology of late-onset sepsis among very preterm infants underscore the need for innovative and organism-specific prevention strategies.

Flannery DD, Edwards EM, Coggins SA, et al. Late-Onset Sepsis Among Very Preterm Infants. Pediatrics.2022;150(6):e2022058813