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Necrotizing pneumonia due to Panton-Valentine leukocidin-producing strains of Staphylococcus aureus is associated with a high mortality rate. We sought factors associated with vital outcome in 50 cases occurring from 1986 through 2005.We compared the clinical and biological characteristics of 50 patients according to their vital outcome and examined the characteristics of the corresponding S. aureus isolates.The overall mortality rate was 56%, and the median survival time was 10 days. All of the deaths were attributed to S. aureus infection and were secondary to refractory shock and/or respiratory failure. Fatal outcome was associated with classical severity factors, such as the need for mechanical ventilation or inotrope support, and with onset of the acute respiratory distress syndrome. Airway bleeding was strongly associated with fatal outcome (P = .002). Patients who had focal staphylococcal infection before the onset of pneumonia had a significantly lower mortality rate (P = .002). The main biological feature associated with death was leukopenia (P Airway bleeding, erythroderma, and leukopenia are associated with fatal outcome from Panton-Valentine leukocidin-positive S. aureus necrotizing pneumonia. More work is needed to develop more efficacious therapy against this highly lethal disease.