Epidemiology and Attributable Mortality of Invasive Staphylococcus aureus Infections in Hospitalized Infants

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Abstract Background Historically, Staphylococcus aureus has been a leading cause of morbidity and mortality in the neonatal intensive care unit (NICU). Given that the burden of invasive S. aureus infection in the NICU is currently unknown, we set out to estimate the incidence and attributable mortality of invasive S. aureus infection among hospitalized infants in the United States. Methods From a national convenience sample of 315 NICUs, we retrospectively identified infants aged ≥4 postnatal days who were hospitalized in a participating NICU. Invasive S. aureus infection incidence was calculated per 10,000 infants, and an emulated trial design was employed to discern differences in mortality between infants with invasive S. aureus infections and otherwise similar infants who did not experience invasive S. aureus infections. Results From the 468,201 infants eligible for analysis, 1,724 infants experienced 1,762 infections for an overall incidence of 37.6 invasive S. aureus infections per 10,000 infants. Most infants with invasive infections were ≤32 weeks’ gestational age (80.9%), very low birthweight (VLBW) <1,500 grams (76.5%), and had a central line during their hospital stay (87.5%). Invasive infections mostly included bloodstream infections (85.4%), and 65.8% of infections occurred within 4 to 28 postnatal days of age. Birthweight inversely correlated with incidence; VLBW infants experienced a >20-fold higher incidence relative to infants born weighing ≥1,500 grams (227.1 vs 10.1 infections per 10,000 infants, respectively). Most deaths following invasive infection (90.4%) occurred among VLBW infants. Compared to otherwise similar infants, infants who experienced an invasive S. aureus infection had an absolute increase in mortality of 5.3% (95%CI: 3.8, 6.8). Conclusions Invasive S. aureus infection and subsequent attributable mortality disproportionally impact VLBW infants. Targeted infection prevention and control measures are necessary to reduce morbidity and mortality from invasive S. aureus infections in this vulnerable population.

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