{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:44:18Z","timestamp":1785725058687,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management.<\/jats:p>","DOI":"10.3390\/ph19081207","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrapleural Fibrinolytic Therapy in the Management of Pediatric Pleural Empyema: A Narrative Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"first","affiliation":[{"name":"Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4601-7484","authenticated-orcid":false,"given":"Valentina","family":"Fainardi","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia Giorgia","family":"Arnesano","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-5568","authenticated-orcid":false,"given":"Nicola","family":"Principi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1136\/thx.2004.030676","article-title":"BTS guidelines for the management of pleural infection in children","volume":"60","author":"Abrahamson","year":"2005","journal-title":"Thorax"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1001\/jamapediatrics.2019.5863","article-title":"Effectiveness of intrapleural tissue plasminogen activator and dornase alfa vs tissue plasminogen activator alone in children with pleural empyema: A randomized clinical trial","volume":"174","author":"Livingston","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1016\/j.vaccine.2019.04.012","article-title":"Significant impact of pneumococcal conjugate vaccination on pediatric parapneumonic effusion: Italy 2006\u20132018","volume":"37","author":"Azzari","year":"2019","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.cmi.2018.10.020","article-title":"Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions\/empyema in Germany, 2010\u20132017: A nationwide surveillance study","volume":"25","author":"Liese","year":"2019","journal-title":"Clin. 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