Trends in Pathogens Causing Late-Onset Sepsis in Very Preterm Infants: 2010–2023

OBJECTIVE To examine long-term trends in overall and pathogen-specific late-onset sepsis (LOS) incidence among very preterm infants (VPIs) in a statewide, population-based network. METHODS We analyzed data for infants born at 22 to 31 weeks’ gestation in the California Perinatal Quality Care Collaborative from 2010 to 2023. LOS was defined as a positive blood and/or cerebrospinal fluid culture obtained more than 3 days after birth. Annual percentage changes (APCs) were estimated using Poisson regression, with and without adjustment for gestational age. RESULTS Among 66 441 VPIs, 6012 (9.0%) had at least 1 LOS episode, with 15.4% mortality. Of 6817 pathogens, 64.7% were gram-positive bacteria, 28.3% gram-negative bacteria, and 7.0% fungi; coagulase-negative staphylococcus (CoNS, 34.5%), Staphylococcus aureus (18.1%), Escherichia coli (10.9%), and Klebsiella species (7.2%) were the most common pathogens. From 2010 to 2017, LOS incidence declined from 15.0% to 8.2% (adjusted APC [aAPC] −5.5% [95% CI, −6.6% to −4.4%]). From 2018 to 2023, LOS incidence increased (aAPC 2.1% [95% CI, 0.6% to 3.6%]), driven by non-CoNS gram-positive (aAPC 5.4% [95% CI, 3.1% to 7.9%]) and gram-negative (aAPC 5.3% [95% CI, 2.4% to 8.2%]) pathogens. S aureus LOS increased in both periods (aAPC 4.3% [95% CI, 1.0% to 7.6%] and 7.7% [95% CI, 4.4% to 11.1%]), and Klebsiella LOS increased during 2018–2023 (aAPC 9.9% [95% CI, 4.2% to 15.8%]). CONCLUSIONS In this contemporary VPI cohort, LOS incidence declined during 2010–2017 but increased thereafter, driven by rising non-CoNS gram-positive and gram-negative infections, particularly S aureus. Targeted prevention strategies should address the evolving pathogen epidemiology of LOS.