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Panton-Valentine leukocidin (PVL) is a necrotizing toxin secreted by Staphylococcus aureus. PVL-positive S. aureus osteomyelitis and arthritis have been described.We analyzed demographic, clinical, laboratory, microbiologic, and imaging data in a study group of 14 pediatric cases with PVL-positive S. aureus osteomyelitis and arthritis diagnosed between 2001 and 2005 and compared results with a control group of 17 pediatric cases of PVL-negative S. aureus osteomyelitis and arthritis treated in our institution during the same period. Treatments and outcome were studied.The severity of PVL-positive S. aureus bone and joint infections was indicated by the presence of severe sepsis in all cases and of septic shock in 6 of the 14 patients. By comparison, severe sepsis was not noted in the control group (P = 0.004). On admission, the median C-reactive protein value was significantly higher in the study group (202.6 mg/L versus 83 mg/L in the control group; P = 0.001). Eleven patients with PVL-positive infection had local extension of the infection by magnetic resonance imaging and 7 patients had severe deep-seated infectious complications by computed tomography. By contrast only 1 patient in the control group presented with bone abscess without extension and none had deep-seated infection (P < 0.001). The median length of hospitalization was 45.5 days in the study group versus 13 days in the control group (P < 0.001). The median duration of intravenous antibacterial chemotherapy was 48 days versus 11.3 days in the control group (P < 0.001). Ten patients (71%) of the study group required surgical procedures with a mean of 3 procedures (range, 1–5) whereas 3 patients (17%) of the control group required 1 surgical drainage each (P = 0.002). All the patients survived, but only 2 patients of the study group were free of long-term complications, whereas there were no long-term complications noted in the control group.PVL-positive S. aureus bone and joint infection is severe and requires prolonged treatment. Local complications are more frequent and often need repeated surgical drainage.