• Based on strong research evidence and clinical experience, most cases of acute hematogenous osteomyelitis begin as an infection in the metaphysis of a long bone that progresses by local extension and potentially can rupture into an adjacent joint or subperiosteal space, especially if appropriate treatment is delayed. The most common infectious agent causing acute hematogenous osteomyelitis in childhood is S aureus. Osteomyelitis in neonates has a more varied etiology that, in addition to S aureus, includes S agalactiae and the Enterobacteriaceae. (1)(2)(3) • Based on strong research evidence and clinical experience, the clinical presentation of osteomyelitis is primarily focal pain at the site of infection and reduced function of the involved limb or structure due to exacerbation of pain with activity. Most patients are also febrile and have modest peripheral leukocytosis and elevated serum acute inflammatory phase reactants, especially C-reactive protein, at presentation. The diagnosis is confirmed definitively by recovery of the pathogen through aspiration of the metaphyseal or subperiosteal infection or by recovery of the organism from blood cultures obtained from a patient who has symptoms, signs, laboratory findings, and imaging modalities consistent with skeletal infection. (1)(5) • Based on some research experience as well as consensus, the diagnosis of osteomyelitis can be supported by imaging studies, with triphasic 99mtechnetium scanning and MRI being the preferred modalities due to increased precision in the diagnosis of acute osteomyelitis in the early phase of disease, especially when the infection occurs in the pelvis, vertebrae, or intervertebral disc space. (4)(6)(7)(8) • Based on strong research evidence as well as consensus, anti-infective therapy for osteomyelitis is determined by isolate recovery and identification, antimicrobial susceptibility testing in vitro, and prescription of an antibiotic regimen likely to deliver therapeutic concentrations to the site of infection, as predicted by testing in vivo. Transition from parenteral to oral antibacterial therapy, when clinically allowed, is appropriate, and serum bactericidal concentrations determined against the patient's isolate can be used as a predictor of probable success of orally administered anti-infective therapy. (9)(10)(11)(12) • Based on some research evidence as well as consensus, the duration of antimicrobial treatment of acute hematogenous osteomyelitis is generally 3 to 4 weeks and should continue until resolution of local and systemic inflammatory symptoms and signs, recovery of painless function of the affected area, and diminution of serum markers of acute inflammation, specifically C-reactive protein, to normal values. (13)(14).