Once Daily Intrapleural Enzyme Therapy in Complicated Parapneumonic Effusion or Empyema

Inclusion Criteria:

* Written informed consent obtained from patient or patient's legally authorized representative (LAR) to participate in the study and HIPAA authorization for release of personal health information.
* Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
* Age ≥ 18 years at the time of consent.
* Patient is admitted to the hospital and with a pleural effusion that is drained with a small-bore chest tube or one that allows for administration of IET
* Pleural fluid that is one of the following:

  (i) Macroscopically purulent or pleural fluid gram stain or culture positive for bacteria (ii) potential of hydrogen (pH) \< 7.2 (iii) Pleural fluid glucose \< 60mg/dL (iv) Pleural fluid Lactate Dehydrogenase (LDH) \> 1,000 IU/L
* Patient is deemed a candidate to receive intrapleural enzyme therapy as defined by having a residual collection or persistent sepsis 24 hours after initial chest tube placement

Exclusion Criteria:

* Known pregnancy or lactating females
* Prisoners
* Age \<18 years at time of consent
* Previous treatment with intra-pleural fibrinolytic agents, DNase, or both during the same hospital admission
* Known sensitivity or allergic reaction to DNAse or tPA
* Coincidental stroke, major hemorrhage (requiring blood transfusions within the last 5 days), major trauma, or major surgery within the last 5 days
* Previous pneumonectomy or active bronchopleural fistula on the affected side
* Therapeutic systemic anticoagulation or antiplatelet agents that cannot held for more than 48 hours prior to IET administration
* Expected survival of less than 3 months due to a pathologic condition other than that causing the pleural infection