<i>Staphylococcus aureus</i> Infections in Infants Admitted to the NICU

Source: Jennings MR, Elhaissouni N, Colantuoni E, et al. Epidemiology and mortality of invasive Staphylococcus aureus infections in hospitalized infants. JAMA Pediatr. 2025;179(7):747-755; doi: 10.1001/jamapediatrics.2025.0429.Investigators from Johns Hopkins University, Baltimore, MD, and Duke University, Durham, NC, conducted a retrospective study to determine the incidence and attributable mortality of late-onset invasive Staphylococcus aureus infection among infants admitted to a NICU. For the study, the reviewed data in the Pediatrix BabySteps Clinical Data Warehouse, which includes demographic and clinical information on infants admitted to 315 NICUs in the US and Puerto Rico and is managed by the Pediatrix Medical Group. Data on infants admitted between 2016 and 2021 were abstracted for study analyses. The primary study outcome was late onset invasive S. aureus infection, defined as a positive culture obtained from an abscess, blood, cerebrospinal fluid, peritoneum, or pleural fluid in a patient ≥4 days old. The main secondary outcome was S. aureus mortality, which was a death in an infant within 7 days of their first positive culture. To estimate S. aureus attributable mortality, the rate of death among infants with an invasive S. aureus infection occurring at a postnatal age of 4–28 days was compared to that in a group of infants without S. aureus, after matching on multiple characteristics. Outcomes were assessed among infants with birth weights >1,500 grams, those with very low birth weight (VLBW, <1,500 grams), and those with birth weights <750 grams.Data on 468,201 infants were included in the analysis, including 12.7% with VLBW. There were 1,762 late-onset invasive S. aureus infections in 1,724 patients (0.4% of the study population). Blood stream infections accounted for 85.4% of all positive cultures. Among infants with S. aureus infections, 80.9% were born at ≤32 weeks’ gestation, 76.5% were VLBW, and 87.5% had a central line placed during their NICU admission. Overall, the incidence of late-onset S. aureus infection was 37.6/10,000 hospitalized infants (95% confidence interval [CI], 35.9, 39.4). The incidence in those with birth weights >1,500 grams was 10.1 (95% CI, 9.1, 11.1), compared to 227.1 (95% CI, 215.3, 239.4) in those with VLBW and 601.2 (95% CI, 557.8, 646.8) for those weighing <750 grams at birth. The overall mortality rate in patients with S. aureus during their NICU admission was 12.1% vs 1.0% for those without S. aureus. For those with late-onset invasive S. aureus infections who died, 90.4% were VLBW. The mortality attributable to late-onset S. aureus infection was 5.3% (95% CI, 3.8, 6.8).The authors conclude that among infants admitted to the NICU, late-onset invasive S. aureus infection and attributable mortality was most common in VLBW infants.Dr Chang has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Late-onset sepsis continues to pose significant risks of morbidity and mortality for infants in the NICU, especially in the very preterm and VLBW populations.1 In contrast to early onset sepsis,2 S. aureus is a common etiologic agent of late-onset sepsis.1 Similar to the findings of a previous study that used the same NICU database to examine S. aureus infections between 1997 to 2012,3 the current authors found that the incidence of invasive S. aureus infections and subsequent mortality continues to occur disproportionately in VLBW infants.The large cohort size and geographic diversity are strengths of the current study. The inability to determine whether the infections were due to methicillin-sensitive S. aureus (MSSA) versus methicillin-resistant S. aureus (MRSA) is a notable limitation. As discussed in the accompanying editorial,4 knowledge of the incidence of MSSA and MRSA infections has important implications for antimicrobial stewardship in terms of reducing empiric vancomycin use in the NICU. Older studies have found that MSSA accounts for a greater proportion of S. aureus infections than MRSA,4 but whether these proportions have shifted in the past decade is unclear.In addition, the current authors do not report which of the infants in their cohort have been admitted since birth and whether any were readmitted from the community. The incidence of invasive S. aureus infections may be different for premature infants who are discharged and then readmitted with illness.5 This differentiation, along with gestational age and birth weight, as the study demonstrates, also are important factors to consider for antimicrobial choice and stewardship when treating infants hospitalized in the NICU.The incidence and mortality of late-onset invasive S. aureus infections are highest in VLBW infants hospitalized in the NICU.Recognition of the persistence of S. aureus infections in premature infants despite hand hygiene, standardized care bundles, and, in some NICUs, surveillance cultures, highlights the need for investigation of novel prevention strategies (eg, parental and health care worker decolonization).4