Epidemiology and Mortality of Invasive Staphylococcus aureus Infections in Hospitalized Infants

Importance Historically, Staphylococcus aureus has been a leading cause of morbidity and mortality in the neonatal intensive care unit (NICU). The current incidence and attributable mortality of late-onset invasive S aureus infection in hospitalized infants is unknown. Objective To estimate the incidence and attributable mortality of late-onset S aureus infection among hospitalized infants in the US. Design, Setting, and Participants This retrospective cohort study included an emulated trial among a national convenience sample of 315 NICUs within the US between 2016 and 2021. Participants were infants aged at least 4 postnatal days who were hospitalized in a participating NICU. Data were analyzed from May to August 2024. Exposures The primary exposures were birth weight and postnatal age. Main Outcomes and Measures The outcomes were the incidence and attributable mortality of late-onset invasive S aureus infection. Methicillin-resistant and methicillin-sensitive S aureus classification was not universally available; thus, all invasive S aureus infections were pooled. Results From 468 201 infants (260 491 [55.6%] male; median [IQR] gestational age, 36 [33-38] weeks) eligible for analysis, 1724 infants experienced 1762 infections for an overall incidence of 37.6 (95% CI, 35.9-39.4) invasive S aureus infections per 10 000 infants. Most infants with invasive infections were 32 weeks’ gestational age or younger (1394 infants [80.9%]), very low birth weight (VLBW; ie, <1500 g) (1318 infants [76.5%]), and/or had a central line during their hospital stay (1509 infants [87.5%]). Invasive infections mostly included bloodstream infections (1505 infections [85.4%]), and 1160 infections (65.8%) occurred within 4 to 28 postnatal days. Birth weight inversely correlated with incidence: infants with VLBW experienced a more than 20-fold higher incidence relative to infants born weighing at least 1500 g (227.1 [95% CI, 215.3-239.4] vs 10.1 [95% CI, 9.1-11.1] infections per 10 000 infants). Most deaths following invasive infection occurred among VLBW infants (189 of 209 deaths [90.4%]). Compared with matched infants without a late-onset invasive S aureus infection, infected infants had an absolute difference in mortality rate of 5.3% (95% CI, 3.8%-6.8%). Conclusions and Relevance This cohort study found late-onset invasive S aureus infection and subsequent attributable mortality disproportionally affected infants with VLBW. Targeted infection prevention and control measures are necessary to reduce morbidity and mortality from invasive S aureus infections in this vulnerable population.