• Adnan Majid, Fayez Kheir, Alejandro Folch, Sebastian Fernandez-Bussy, Sumit Chatterji, Ashish Maskey, Meghan Fashjian, George Cheng, Sebastian Ochoa, Daniel Alape, and Erik Folch.
• 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
• Ann Am Thorac Soc. 2016 Sep 1; 13 (9): 1512-8.

RationaleTreatment of pleural infection with instillation of intrapleural tissue plasminogen activator (tPA) and human recombinant DNase (DNase) has been proven to decrease the length of hospital stay, decrease surgical referral, and improve drainage. The optimal dosage, administration, timing, and frequency of the regimen remain unclear. It is unknown if the two drugs can be administered immediately one after the other (referred to as concurrent) instead of instilling them separately with a 1- to -2-hour interval in between.ObjectivesTo assess the safety and efficacy of concurrent instillation of intrapleural tPA/DNase guided by radiographic and clinical response in patients with pleural infection.MethodsWe conducted a retrospective cohort study. Consecutive patients with pleural infection who received concurrent tPA/DNase were included. The initiation and number of doses of tPA/DNase therapy were based on pleural fluid drainage, clinical response, and radiographic findings.Measurements And Main ResultsSeventy-three patients received concurrent tPA/DNase therapy. Treatment was successful in 90.4% of them; 80.8% were effectively treated with fewer than six doses of therapy (median, 2; interquartile range [IQR], 1-3.5); and 71.2% received their first dose of tPA/DNase within 24 hours after chest tube insertion. The median hospital stay from the first dose of tPA/DNase to discharge was 7 days (IQR, 5-11 d). The volume of pleural fluid drained increased from a median of 295 ml (IQR, 97.5-520 ml) 24 hours before treatment to a median of 1,102 ml (IQR, 627-2,200 ml) 72 hours following therapy (P < 0.001). Nonfatal pleural bleeding occurred in 5.4%, 15.1% had chest pain, and 2.7% died as a result of pleural infection.ConclusionsThis cohort study shows that early administration of concurrent tPA/DNase in patients with pleural infection is relatively safe and effective. Given the high cost of therapy, it is feasible to guide therapy on the basis of clinical and radiographic response.

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