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RARE DISEASE
Pleural empyema
Pleural empyema
Pleural empyema
Drug discovery
2
drugs
With orphan designations
Overview
Pleural empyema, a collection of pus in the pleural space, typically arises from complications of pneumonia, thoracic procedures, or trauma. It progresses through exudative, fibrinopurulent, and organized stages, causing symptoms like chest pain, fever, and respiratory compromise [1][6][11]. Diagnosis involves imaging and pleural fluid analysis, while treatment combines antibiotics, drainage (thoracentesis/chest tubes), intrapleural fibrinolytics, and surgery (VATS/decortication) for advanced cases [3][8][13]. Mortality ranges from 6.9% to 16.1%, with rising incidence linked to aging populations and influenza [4][12][17].
Population
Incidence rising globally, particularly in elderly males and those with comorbidities (diabetes, COPD, asthma) [4][9][17].
Seasonal correlation with influenza peaks, especially in children and young adults [14][19].
Higher risk in patients with poor dental hygiene, immunosuppression, or thoracic trauma [5][7][11].
Therapies
Early-stage: Antibiotics + image-guided thoracentesis or small-bore chest tubes [1][13].
Loculated effusions: Intrapleural fibrinolytic therapy (e.g., alteplase/DNase) to enhance drainage [8][13].
Advanced cases: VATS or open decortication for lung re-expansion, achieving 83-98% success rates [3][17][12].
Categories: rare respiratory diseases
Research Papers
1,834 drug discovery papers related to Pleural empyema, with 3 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,834 drug discovery papers related to Pleural empyema, with 3 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-06 | Metagenomic Analysis of Thoracic Empyema Etiology Through Next-Generation Sequencing Enhances Conventional Culture Techniques.
This study aimed to analyze the microbiome of thoracic empyema using metagenomic methods and compare the results with conventional culture methods to increase diagnostic accuracy and enhance antibiotic therapy. This study involved 30 patients with thoracic empyema from hospitals in Riau Province, Indonesia. Pleural fluid samples were collected for culture analysis and identification using the Vitek 2 compact system and metagenomic analysis. Patient clinical data were also collected. Culture methods showed a 40.0% positive rate, with Gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa) predominating. Metagenomics showed a 56.7% positive rate, identifying a more diverse microbiome, including fungi (29.4% abundance), other Gram-negative bacteria (26.5%), and anaerobic bacteria (22.5%). Comparison of the two methods showed 36.7% complete agreement and 23.3% partial agreement, with 40% disagreement, with a Kappa coefficient of 0.416 and P-value of 0.016 (P<0.050). Metagenomic NGS offers significant advantages in detecting the microbiome of thoracic empyema, particularly fungi and anaerobic bacteria, which are often missed by conventional culture methods. This has the potential to improve diagnostic accuracy and optimize antibiotic therapy. Further research with larger sample sizes is needed.
2026-07-03 | Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa: A Multicenter Retrospective Cohort Study.
Intrapleural tissue plasminogen activator (tPA) and DNase are used when drainage of loculated pleural effusions is inadequate, but the real-world performance of pragmatic once-daily protocols remains uncertain. We performed a retrospective cohort study across seven hospitals between January 1, 2019, and December 31, 2020. Adults who received intrapleural tPA 20 or 50 mg once daily with optional DNase 5 mg once daily for complicated pleural effusion, empyema, or hemothorax were included. The primary outcome was treatment success, defined as survival to hospital discharge without surgical intervention during the index admission. Secondary outcomes included chest tube drainage change, hospital length of stay, ICU length of stay, mortality, major bleeding, and peri-procedural pain requiring analgesics. A post hoc subgroup analysis compared monotherapy with combination therapy. Among 120 included patients, treatment success occurred in 102 (85.0%; 95% CI, 77.3%-90.9%). The median paired increase in chest tube drainage was 487.5 mL (IQR, 72.5-979.0; P < .001). Major bleeding occurred in one patient (0.8%), whereas peri-procedural pain requiring additional analgesia occurred in 69 (57.5%). In the exploratory subgroup analysis, treatment success was 83.8% with tPA monotherapy and 87.0% with tPA/DNase combination therapy. In this multicenter real-world cohort, standardized intrapleural tPA with or without DNase was associated with high observed treatment success, substantial increases in drainage, and rare major bleeding. Comparative findings between combination therapy and monotherapy should be interpreted cautiously because treatment allocation was nonrandomized and exposure groups were imbalanced.
2026-06-29 | Comparison of Early Intrapleural Fibrinolytic Therapy, Versus Administration After Failure of Intercostal Drainage in Children with Empyema Thoracis: A Systematic Review.
Intrapleural fibrinolytic therapy (IPFT) is widely used in pediatric empyema thoracis. Some physicians administer it early (when empyema is confirmed) whereas others try it after intercostal drainage (ICD) has failed. The optimal timing of IPFT administration is unclear. To compare early IPFT (i.e. as an initial therapy when empyema is diagnosed), versus IPFT administered after failure of ICD, in children with empyema thoracis. Literature search was conducted through PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, and two grey literature databases. Additional searches in four clinical trials registries, and hand-searching were conducted. The goal was to identify randomized controlled trials (RCT) comparing early IPFT (as an initial therapy, upon the diagnosis of empyema), versus delayed IPFT (i.e. administered after failure of ICD), in children with empyema thoracis (diagnosed by standard criteria). The outcomes recorded were clinical recovery, need for surgery, hospital stay, and safety. The literature search yielded 2907 citations across the 11 databases examined. However, there were no RCTs directly addressing the review question. Indirect evidence from pediatric trials suggested that early IPFT may reduce pleural thickening and hospital stay, although decrease in surgery was not demonstrated consistently. In contrast, some observational studies reported high success rates with IPFT administered after failure of ICD, with avoidance of surgery in many cases. There is no RCT evidence comparing the initial administration of IPFT versus administration after failure of ICD. Well-designed RCTs are urgently needed.
2026-07-06 | Metagenomic Analysis of Thoracic Empyema Etiology Through Next-Generation Sequencing Enhances Conventional Culture Techniques.
This study aimed to analyze the microbiome of thoracic empyema using metagenomic methods and compare the results with conventional culture methods to increase diagnostic accuracy and enhance antibiotic therapy. This study involved 30 patients with thoracic empyema from hospitals in Riau Province, Indonesia. Pleural fluid samples were collected for culture analysis and identification using the Vitek 2 compact system and metagenomic analysis. Patient clinical data were also collected. Culture methods showed a 40.0% positive rate, with Gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa) predominating. Metagenomics showed a 56.7% positive rate, identifying a more diverse microbiome, including fungi (29.4% abundance), other Gram-negative bacteria (26.5%), and anaerobic bacteria (22.5%). Comparison of the two methods showed 36.7% complete agreement and 23.3% partial agreement, with 40% disagreement, with a Kappa coefficient of 0.416 and P-value of 0.016 (P<0.050). Metagenomic NGS offers significant advantages in detecting the microbiome of thoracic empyema, particularly fungi and anaerobic bacteria, which are often missed by conventional culture methods. This has the potential to improve diagnostic accuracy and optimize antibiotic therapy. Further research with larger sample sizes is needed.
2026-07-03 | Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa: A Multicenter Retrospective Cohort Study.
Intrapleural tissue plasminogen activator (tPA) and DNase are used when drainage of loculated pleural effusions is inadequate, but the real-world performance of pragmatic once-daily protocols remains uncertain. We performed a retrospective cohort study across seven hospitals between January 1, 2019, and December 31, 2020. Adults who received intrapleural tPA 20 or 50 mg once daily with optional DNase 5 mg once daily for complicated pleural effusion, empyema, or hemothorax were included. The primary outcome was treatment success, defined as survival to hospital discharge without surgical intervention during the index admission. Secondary outcomes included chest tube drainage change, hospital length of stay, ICU length of stay, mortality, major bleeding, and peri-procedural pain requiring analgesics. A post hoc subgroup analysis compared monotherapy with combination therapy. Among 120 included patients, treatment success occurred in 102 (85.0%; 95% CI, 77.3%-90.9%). The median paired increase in chest tube drainage was 487.5 mL (IQR, 72.5-979.0; P < .001). Major bleeding occurred in one patient (0.8%), whereas peri-procedural pain requiring additional analgesia occurred in 69 (57.5%). In the exploratory subgroup analysis, treatment success was 83.8% with tPA monotherapy and 87.0% with tPA/DNase combination therapy. In this multicenter real-world cohort, standardized intrapleural tPA with or without DNase was associated with high observed treatment success, substantial increases in drainage, and rare major bleeding. Comparative findings between combination therapy and monotherapy should be interpreted cautiously because treatment allocation was nonrandomized and exposure groups were imbalanced.
2026-06-29 | Comparison of Early Intrapleural Fibrinolytic Therapy, Versus Administration After Failure of Intercostal Drainage in Children with Empyema Thoracis: A Systematic Review.
Intrapleural fibrinolytic therapy (IPFT) is widely used in pediatric empyema thoracis. Some physicians administer it early (when empyema is confirmed) whereas others try it after intercostal drainage (ICD) has failed. The optimal timing of IPFT administration is unclear. To compare early IPFT (i.e. as an initial therapy when empyema is diagnosed), versus IPFT administered after failure of ICD, in children with empyema thoracis. Literature search was conducted through PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, and two grey literature databases. Additional searches in four clinical trials registries, and hand-searching were conducted. The goal was to identify randomized controlled trials (RCT) comparing early IPFT (as an initial therapy, upon the diagnosis of empyema), versus delayed IPFT (i.e. administered after failure of ICD), in children with empyema thoracis (diagnosed by standard criteria). The outcomes recorded were clinical recovery, need for surgery, hospital stay, and safety. The literature search yielded 2907 citations across the 11 databases examined. However, there were no RCTs directly addressing the review question. Indirect evidence from pediatric trials suggested that early IPFT may reduce pleural thickening and hospital stay, although decrease in surgery was not demonstrated consistently. In contrast, some observational studies reported high success rates with IPFT administered after failure of ICD, with avoidance of surgery in many cases. There is no RCT evidence comparing the initial administration of IPFT versus administration after failure of ICD. Well-designed RCTs are urgently needed.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Pleural empyema.
2 orphan drug designations for Pleural empyema.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Single-chain urokinase plasminogen activator | proteins | EMA | 2014-12-16 | — | Scendea (NL) B.V. |
single chain urokinase plasminogen activator | proteins | FDA | 2014-09-11 | — | Lung Therapeutics, Inc. |
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