Bacteremia and infective endocarditis (IE) are important causes of morbidity and mortality associated with Staphylococcus aureus infections. Increasing exposure to healthcare, invasive procedures, and prosthetic implants has been associated with a rising incidence of S. aureus bacteremia (SAB) and IE since the late twentieth century. S. aureus is now the most common cause of bacteremia and IE in industrialized nations worldwide and is associated with excess mortality when compared to other pathogens. Central tenets of management include identification of complicated bacteremia, eradicating foci of infection, and, for many, prolonged antimicrobial therapy. Evolving multidrug resistance and limited therapeutic options highlight the many unanswered clinical questions and urgent need for further high-quality clinical research.

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Background The impact of early adequate empirical antibiotic therapy on outcomes of infants in the neonatal intensive care unit (NICU) who develop Staphylococcus aureus bloodstream infection (BSI) is unknown. Methods Infants with S. aureus BSI discharged in 1997–2012 from 348 NICUs managed by the Pediatrix Medical Group were identified. Early adequate empirical antibiotic therapy was defined as exposure to ≥1 antibiotic with anti-staphylococcal activity on the day the first positive blood culture was obtained. All other cases were defined as inadequate empirical antibiotic therapy. We evaluated the association between inadequate empirical antibiotic therapy on outcomes controlling for gestational age, small-for-gestational-age status, gender, discharge year, mechanical ventilation, inotropic support, and use of supplemental oxygen. The primary outcome was 30-day mortality. Secondary outcomes were 7-day mortality, death before hospital discharge, and length of bacteremia. Results Of the 3339 infants with S. aureus BSI, 2492 (75%) had methicillin-susceptible S. aureus (MSSA) BSI and 847 (25%) had methicillin-resistant S. aureus (MRSA) BSI. Inadequate empirical antibiotic therapy was administered in 725 (22%) cases. Inadequate empirical antibiotic therapy was associated with increased 30-day mortality (odds ratio, 2.03 [95% confidence interval, 1.08, 3.82]) among infants with MRSA BSI. Inadequate empirical antibiotic therapy was not associated with increases in mortality among infants with MSSA BSI. Conclusions After controlling for confounders, inadequate empirical antibiotic therapy was associated with a modestly increased mortality at 30 days for infants with MRSA BSI.

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