Acute hematogenous osteomyelitis (AHO) is commonly complicated by Staphylococcus aureus bacteremia (SAB), yet there is a lack of information regarding the recommended time of parenteral antibiotics before transitioning to oral antibiotics. The purpose of this study was to assess the usefulness of severity of illness score (SIS) in guiding treatment decisions in this environment by analyzing clinical outcomes linked with an early transfer to oral antimicrobial medication among children hospitalized at an institution with AHO and SAB. Researchers looked back at all the cases of AHO and SAB in children hospitalized in a hospital between 2009 and 2018 and used a validated SIS to categorize them into mild (0-3), moderate (4-7), and severe (8-10) groups. Treatment (such as duration of parenteral and oral antibiotics and operations) and clinical response were compared across groups (eg, bacteremia duration, acute kidney injury, length of stay, and treatment failure). For the 246 kids diagnosed with AHO and SAB, the median duration of parenteral antibiotics was significantly different across the mild (n = 80), moderate (n=98), and severe (n=68) groups (3.6 days, 6.5 days, and 14.3 days, respectively; P≤0.001). SIS cohorts also differed with regard to number of surgeries (0.4 vs. 1.0 vs. 2.1; P≤0.001), duration of bacteremia (1.0 vs. 2.0 vs. 4.0 days; P≤0.001), acute kidney injury (0.0% vs. 3.0% vs. 20.5%; P≤0.001), hospital length of stay (4.8 vs. 7.4 vs. 16.4 days; P≤0.001) and total duration of antibiotics (34.5 vs. 44.7 vs. 60.7 days; P≤0.001). In patients with mild or moderate SIS, switching to oral antibiotic therapy early was not related to treatment failure despite SAB. Classifying the severity of SAB may help guide treatment decisions for children with AHO, who are at increased risk for developing a variety of illnesses. It looks safe to switch children with mild or moderate AHO and SAB to oral antibiotic treatment early.