Prolonged Intrapleural Fibrinolytic Therapy in a Patient with Complex Empyema: A Case Report

Background: Pleural infection, particularly empyema, remains a critical challenge in respiratory medicine. The MIST-2 trial established the standard six-dose regimen of intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) as a non-surgical management strategy. However, the optimal duration of this therapy for patients with persistent, complex loculations or those who are poor surgical candidates remains undefined. Case Presentation: We report the case of a 62-year-old man with severe co-morbidities, including morbid obesity and New York Heart Association Class III diastolic heart failure, who developed a complex, loculated left-sided pleural empyema due to a polymicrobial infection (Gemella sanguinis and Escherichia coli). Given his prohibitive surgical risk, he was deemed a non-candidate for video-assisted thoracoscopic surgery (VATS). Following an incomplete response to the standard six-dose intrapleural fibrinolytic therapy (IPFT) regimen, an empirical extension was initiated, resulting in a total of 12 doses of tPA (10 mg) and DNase (5 mg) administered over six days. Outcome: The patient achieved marked clinical and radiological resolution of the empyema, with complete lung re-expansion and no observed complications, specifically no intrapleural hemorrhage. Conclusion: This case provides compelling evidence that an extended course of IPFT can be a safe and effective, definitive non-surgical treatment option for high-risk patients with complex, persistent pleural infections. It supports a paradigm shift towards an individualized, response-guided approach to IPFT duration, challenging the fixed-dose protocol of the MIST-2 trial in selected clinical scenarios.