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Intrapleural urokinase therapy in a neonate with pleural empyema. Pleural empyema is rare in neonates, and treatment with systemic antibiotics and tube drainage may fail because of the thick viscous fluid, bacterial products with fibrin deposition, and multiple loculations. Intrapleural fibrinolytic therapy with urokinase is an effective and non-invasive treatment option that avoids surgical intervention, although its use in neonates has not been studied extensively. In this report, we describe the case of a 13-day-old male neonate with Escherichia coli sepsis and pneumonia, which rapidly progressed to parapneumonic effusion and pleural empyema. After inadequate response to i.v. antibiotics and chest tube drainage, the patient was successfully treated with intrapleural urokinase.