Background: Acute osteomyelitis still represents a significant clinical challenge, with an increasing incidence in paediatric population. A careful assessment and a rapid diagnosis with proper timing and choice of empirical antimicrobial therapy are necessary to avoid sequelae. The initial treatment should consist of empirical antibiotic therapy, to cover the major responsible pathogens in each age group.

Data sources: We made a literature search with PubMed and Cochrane database from 2000 to 2019 in English, French, and Spanish languages using the key words “osteomyelitis, children, clinical, diagnosis, and treatment”.

Results: The child’s clinical features, age, and the microbiological profile of the geographic area should be evaluated for diagnosis and in the choice of antibiotic treatment. Latest data suggest the administration of intravenous antibiotics for a short period, with subsequent oral therapy, according to the improvement of clinical status and inflammatory markers. For children older than 3 months, the shift to oral medications is already possible after a short course of intravenous therapy, until recovery. The timing for the shift from cefazolin to cephalexin or cefuroxime, intravenous clindamycin to oral clindamycin, and intravenous ceftriaxone + oxacillin to oral equivalents will be decided according to the improvement of clinical status and inflammatory markers. We also present the approach to osteomyelitis due to difficult pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL)-positive S. aureus infections.