title: Intrapleural agents for pleural infection:  fibrinolytics and beyond.
abstract: OBJECTIVE
  Pleural infection is a common, increasing clinical problem with a high morbidity and mortality. Medical management of pleural infection often fails, requiring invasive thoracic surgery to drain infected pleural collections, and for many years intrapleural agents have been assessed to reduce the need for surgical drainage and improve clinical outcomes. Randomized trials assessing intrapleural fibrinolytic agents have given conflicting results, and recent evidence provides important information on the role of intrapleural agents in the treatment of pleural infection, and the possible biology associated with infection progression in these patients.
  
  
  RESULTS
  Pleural infection is increasing in both the adult and paediatric populations. The combined previous evidence assessing intrapleural fibrinolytics alone in pleural infection suggests lack of efficacy for clinically important outcomes. The Multi-Centre Intrapleural Sepsis Trial 2 (MIST2) study provides the first evidence of a novel treatment combination [intrapleural tissue plasminogen activator (tPA) combined with intrapleural deoxyribonuclease (DNase)], which significantly improves the chest radiograph compared with either agent alone or placebo, and has potentially important benefits to important clinical outcomes (need for surgery and hospital stay). The precise mechanism of action of combination fibrinolytic and DNase in pleural infection is speculative.
  
  
  CONCLUSIONS
  Fibrinolytic therapy alone has not been proven to be of use in the treatment of pleural infection. The MIST2 study provides clear-cut evidence demonstrating improved chest radiographs, and highly suggestive secondary outcomes suggesting improved clinically important outcomes, using a combination of intrapleural tPA and DNase. This novel treatment combination may represent an important step in our understanding and treatment of pleural infection; however, larger clinical studies specifically addressing important clinical outcomes and further laboratory research describing the potential mechanisms of action are now required.
authors.affiliation: Oxford Centre for Respiratory Medicine, Oxford University Hospitals, Headington, Oxford X3 7LJ, UK. rahman@ndm.ox.ac.uk
authors.forename: Najib M
authors.initials: NM
authors.lastname: Rahman
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003851:Deoxyribonucleases / Q000627:therapeutic use*; D004322:Drainage; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D010994:Pleura / Q000503:physiopathology; D010995:Pleural Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D003851:Deoxyribonucleases; D010959:Tissue Plasminogen Activator