Neonatal Osteomyelitis Caused by Staphylococcus aureus: Case Series and Review of the Literature.

Background:Staphylococcus aureus neonatal osteomyelitis (SA-NOm) is a rare condition with the potential for lifelong skeletal morbidity. Available evidence remains scarce and inconsistent, with notable differences in clinical presentation, therapeutic regimens, and reported outcomes, underscoring the need for a systematic evaluation combining clinical experience with existing literature. Methods: We retrospectively reviewed data from all neonates admitted to Regina Margherita Children's Hospital, Turin, Italy, between 2017 and 2024 with a diagnosis of SA-NOm. A structured narrative review of the pertinent literature published over the past 25 years was conducted to identify additional cases and compare management approaches. Results: Four neonates with SA-NOm were identified at our center (institutional cohort) while a literature review retrieved 38 additional cases (literature cohort) to establish a combined cohort (n = 42). Of these, 78% were born at term, with a male-to-female ratio of 1.6:1 (26 males, 16 females). Approximately half of the combined cohort presented identifiable risk factors for SA-NOm, including neonatal intensive care unit admission, prematurity, sepsis, or maternal complications. Across the combined cohort, the mean age at presentation was 19 days. The most common presenting signs were local swelling and reduced mobility of the affected limb, although systemic symptoms often complicated early recognition. Long bones were most frequently involved-particularly the femur, humerus, and tibia-with equal distribution between upper and lower extremities. The mean intravenous antibiotic duration for the combined cohort was 31.6 days, followed by two to three weeks of oral therapy. Empiric regimens varied, including glycopeptides alone or combined with second- or third-generation cephalosporins, anti-staphylococcal penicillins, or carbapenems. Sequelae rates were rarely reported in the literature, likely due to limited follow-up, whereas extended surveillance in our cohort revealed substantial long-term morbidity, including restricted joint mobility, limb length discrepancy, and persistent radiographic abnormalities. Conclusions: SA-NOm, due to its rarity and potential for long-term skeletal sequelae, requires early diagnosis and timely empiric antibiotic therapy based on local resistance data. Prospective multicenter studies are needed to define standardized diagnostic and therapeutic protocols.