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
1,849 drug discovery papers about Pleural empyema, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,849 drug discovery papers about Pleural empyema, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-07 | Pediatric pyopneumothorax caused by Prevotella oris successfully diagnosed via mNGS: a case report and literature review.
Empyema and pyopneumothorax are severe complications of pediatric community-acquired pneumonia. While typically caused by aerobic bacteria, anaerobic infections, particularly those involving Prevotella oris (P. oris), are exceedingly rare in children. This study aims to explore the clinical characteristics, diagnostic challenges, and therapeutic strategies for pediatric pyopneumothorax caused by P. oris, thereby enhancing clinical awareness of this uncommon opportunistic pathogen. We retrospectively analyzed the clinical data of a 10-year-old male admitted to the Hebei Children's Hospital in October 2025, presenting with acute chest pain and a history of tooth extraction 1 week prior to symptom onset. Radiological imaging revealed bilateral pneumonia with bilateral pleural effusions (predominantly on the left side). Pleural fluid analysis was consistent with an empyema. Traditional bacterial cultures of blood and pleural fluid yielded negative results. However, probe-based targeted metagenomic next-generation sequencing (mNGS) of the pleural fluid identified P. oris with a high relative abundance (81.86%), alongside other minor oral commensals. Based on the molecular diagnosis and the patient's ongoing clinical deterioration, cefoperazone-sulbactam was selected to strengthen coverage against anaerobic Gram-negative organisms, while linezolid was temporarily added to cover potential Gram-positive pleural co-infection during the acute deterioration phase. This was combined with closed thoracic drainage and intrapleural urokinase instillation for fibrinolysis, leading to a complete clinical recovery. Prevotella oris is a rare but significant pathogen in pediatric empyema. A high index of suspicion should be maintained for anaerobic infections in children presenting with a history of dental procedures, abnormal immune parameters or possible immunological vulnerability, or poor response to empirical antibiotics. Traditional cultures are often inadequate; therefore, mNGS serves as a crucial tool for the early detection and precise treatment of difficult-to-culture anaerobes.
2026-07-15 | Adult Empyema Caused by Refractory Methicillin-Resistant Staphylococcus aureus Treated Using Linezolid as Salvage Therapeutic Option: A Report of Two Cases.
The pathogenesis and treatment of pulmonary lesions caused by methicillin-resistant Staphylococcus aureus (MRSA) infection have been unclear because MRSA has usually been considered a colonizer. Two adult cases of MRSA empyema were treated using linezolid (LZD) because they were refractory to the glycopeptides vancomycin (VCM) and teicoplanin (TEIC). Case 1 was a 50-year-old man with a history of lung cancer and pneumothorax who was admitted with pulmonary empyema with a severe dry cough. MRSA empyema was diagnosed because only MRSA was detected by video-assisted thoracoscopy (VATS) from his effusions. He was initially treated using VCM for 10 days, but his inflammatory markers and condition did not so improve; therefore, VCM was switched to LZD. His condition improved with LZD for 14 days. Case 2 was a 77-year-old man with pharyngeal cancer who was admitted with respiratory failure. He was diagnosed with MRSA empyema because only MRSA was detected from his pleural effusions on pleural drainage. He received a TEIC drip infusion for 10 days, but his respiratory status did not so improve; therefore, his treatment was switched to LZD. His condition improved with LZD for 14 days. MRSA empyema was diagnosed in these two cases because only MRSA was detected from pleural effusions. Both patients finally improved following the switch from glycopeptide antibiotics to LZD. These findings suggest MRSA as the true cause of the infections and that LZD, rather than VCM and TEIC, might be effective in cases of MRSA empyema.
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.
antibodies
2025-08-18 | The role of interleukin-6 signalling in pleural infection: observational and genetic analyses.
Pleural infection is associated with marked local and systemic inflammation leading to significant morbidity. It may be possible to therapeutically augment this response and interleukin-6 is a key signalling cascade in inflammatory pathologies. We performed a prospective observational study recruiting patients with pleural effusions secondary to infection and measured interleukin-6 in matched pleural fluid and serum (n = 76). We subsequently performed a large-scale, two sample Mendelian Randomisation study (1601 cases and 830,709 controls), using genetic variation at IL6R to proxy the effect of interleukin-6 inhibition on pleural infection and overcome confounding inherent in observational analyses. Pleural interleukin-6 levels in infection were 5000-fold higher than matched serum levels (median 72,752 pg/ml vs. 15 pg/ml). Pleural interleukin-6 predicted systemic inflammation (neutrophil count, C- reactive protein), correlated with clinical markers of disease severity (effusion size, pH, glucose), and was strongly associated with length of hospital stay. In Mendelian randomisation analyses, interleukin-6 inhibition was predicted to have a large protective effect on the incidence of infection (OR 0.23; 95% CI 0.14-0.39 per standard deviation decrease in C- reactive protein). The effect size was larger than that seen in COVID-19 and coronary artery disease, where interleukin-6 inhibition has been successful in trials. Multiple lines of evidence suggest pleural interleukin-6 drives pathology in pleural infection. Targeting interleukin-6 may hold promise and should be considered in randomised trials. This study has been funded by the National Institutes of Health and Care Research Bristol Biomedical Research Centre.
2024-12-20 | IMMUNOLOGICAL DISORDERS IN PLEURAL EMPYEMA AND THE POSSIBILITY OF THEIR CORRECTION
Abstract. Problems in the treatment of acute pleural empyema are caused by a number of objective and subjective reasons, in particular, such as the widespread spread of antibiotic-resistant microflora and allergization of the population. Literature data indicate the need to improve immunostimulating therapy in patients with pleural empyema. A study of the long-term results of all types of treatment for this pathology shows that they do not give 100% success. The presented data indicate the need to improve immunostimulating therapy in patients with pleural empyema.
2020-10-05 | Precision Targeting of the Plasminogen Activator Inhibitor-1 Mechanism Increases Efficacy of Fibrinolytic Therapy in Empyema
Abstract Plasminogen activator inhibitor-1 (PAI-1) is an endogenous irreversible inhibitor of tissue-type (tPA) and urokinase (uPA) plasminogen activators. PAI-1-targeted fibrinolytic therapy (PAI-1-TFT) is designed to decrease the therapeutic dose of tPA and uPA to attenuate the risk of bleeding and other complications. The docking site peptide (DSP) is a part of the PAI-1 reactive center loop, which interacts with plasminogen activators, thus affecting the PAI-1 mechanism. We used DSP for PAI-1-TFT in two rabbit models: chemically-induced pleural injury and Streptococcus pneumoniae induced empyema. PAI-1-TFT with DSP combined with single chain uPA or tPA resulted in an up to 8-fold decrease in the minimal effective therapeutic dose of plasminogen activator and induced no bleeding. An increase in the level of PAI-1 in infectious pleural injury, when compared to chemically-induced injury, coincided with an increase in the minimal effective dose of plasminogen activator and DSP. PAI-1 is a valid molecular target in S. pneumoniae empyema model in rabbits, which closely recapitulates key characteristics of empyema in humans. Low dose PAI-1-TFT is a novel precise interventional strategy that may improve fibrinolytic therapy of empyema in clinical practice.
2015-07-07 | Salmonella Enteritidis Empyema Preceding the Diagnosis of Non-Hodgkin’s Lymphoma and Subsequent Contralateral Chylothorax Treated with Radiolabelled Rituximab
Salmonella infection is common, but pleural involvement has rarely been reported.Only seven cases of Salmonella enteritidis pleural empyema have been reported; all had an associated preexisting underlying immunosuppresion or malignancy.We report the case of an apparently healthy man who developed S. enteritidis empyema.On further follow-up and surveillance, he eventually presented with non-Hodgkin's lymphoma and a contralateral recurrent chylothorax.The latter was successfully controlled with radiolabeled rituximab, which has never been described for the above purpose in literature before.
2015-05-22 | Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.
A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.
cell therapies
2026-08-12 | Role of omental flaps in thoracic surgery complications: a narrative review.
The greater omentum is a highly vascularized and immunologically active organ with recognized regenerative and antimicrobial properties. Its application in pleural space complications has gained renewed interest with the expansion of minimally invasive harvesting techniques. This review summarizes the current literature regarding the role of omental flaps in the management of post-lobectomy complications. This narrative review was conducted using a comprehensive search of MEDLINE (Via PubMed), Scopus, and Cochrane Central Register of Controlled Trials from database inception through February 2026 using the search terms "Omental flap", "pleural space", and "bronchopleural fistula", "post-lobectomy complications", "entrapped lung" and "empyema". Peer-reviewed articles in English and Spanish were included. Data were extracted and synthesized narratively, focusing on indications, techniques, outcomes, advantages, and limitations. Omental flaps are most used for bronchopleural fistula (BPF), empyema, mediastinitis, and prosthetic graft coverage. Rich vascular and lymphatic networks of the omentum enhance infection control and tissue healing, particularly in contaminated or high-risk fields. The size and pliability of the omentum allow effective obliteration of complex pleural dead space problems and durable coverage of critical structures. Reported flap survival rates range from 80-100% in small case series. Omental flaps represent a versatile and biologically advantageous option for pleural space complications. Although current evidence is limited and largely observational, reported outcomes are promising, warranting further prospective investigation.
2026-06-04 | Surgical management of recurrent MRSA empyema with eloesser flap in a complex thoracic patient: lessons from endobronchial valve failure.
Endobronchial valves (EBVs) have emerged as a minimally invasive option for managing bronchopleural fistula (BPF), with reported efficacy rates of approximately 70-75%. However, their long-term performance in the setting of chronic infection remains poorly characterized, and documentation of specific failure mechanisms is limited. A 74-year-old man with recurrent methicillin-resistant Staphylococcus aureus (MRSA) empyema following right lower lobectomy presented with treatment failure 14 months after Zephyr EBV placement. During Eloesser flap creation, both valves were found displaced from the bronchial stump, with one completely dislodged into the pleural space. The bronchial stump showed evidence of erosion from chronic infection. The patient demonstrated clinical improvement following the Eloesser procedure, with negative cultures at three-month follow-up. This case provides direct intraoperative visualization of EBV displacement in chronic empyema, suggesting that ongoing infection, tissue destruction, and mechanical forces may compromise valve stability over time. The finding supports consideration of patient selection criteria for EBV therapy and demonstrates the continued role of open drainage procedures when minimally invasive approaches fail.
2026-04-04 | Single-stage open window thoracostomy with simultaneous muscle flap transposition and early negative pressure wound therapy for chronic empyema: a propensity score- and machine learning-based study.
BACKGROUND: To compare the clinical efficacy of a single-stage surgical approach combining open window thoracostomy, muscle flap transposition, and early negative pressure wound therapy (NPWT) with that of conventional staged management for chronic empyema. METHODS: This retrospective, single-center cohort included 45 patients with chronic empyema (single-stage, n = 7; conventional, n = 38) who were treated from 2009 to 2024. The primary endpoint was the cavity reduction ratio measured via three-dimensional computed tomography (3D CT). To minimize selection bias, we applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). We prespecified the average treatment effect on the treated (ATT) as the primary estimand, whereas the average treatment effect (ATE) was considered exploratory because treatment assignment was strongly related to bronchopleural fistula (all single-stage patients had BPF) and overlap was limited. The follow-up intervals were linearly normalized to adjust for time-dependent variability. Machine learning models were used as complementary predictive analyses to identify predictors of cavity reduction. RESULTS: After PSM (n = 5 per group), the single-stage group had significantly greater cavity reduction than the conventional group did (90% [89–94%] vs. 37% [32–43%], p = 0.008). The IPTW analysis demonstrated significant treatment effects: 0.38 (95% CI: 0.17–0.59, p = 0.005) for the ATT and 0.63 (95% CI: 0.12–1.14, p = 0.03) for the ATE (exploratory). Machine learning models consistently identified the treatment approach and time-related variables as important predictors of cavity reduction. CONCLUSIONS: Compared with conventional management, the single-stage approach was associated with significantly greater empyema cavity reduction and was feasible even in patients with bronchopleural fistulas. Causal interpretation is most defensible for the ATT, whereas generalization to the full population (ATE) should be considered exploratory due to limited overlap. Despite the small sample size, the consistent findings across diverse analytical frameworks support the single-stage strategy as a promising approach that warrants prospective multicenter validation and clearer criteria for patient selection.
2026-02-12 | An alternative method of closure of open window thoracostomy: a two-staged approach.
Refractory empyema poses significant treatment challenges, but open window thoracostomy (OWT) remains an effective solution, facilitating infection control and promoting recovery. However, after the resolution of infection, patients often face complications due to the open pleural cavity and residual pleural space. The closure of open window thoracostomies is particularly difficult, especially in the presence of large residual spaces and bronchopleural fistulas (BPFs). This case series examines six patients who underwent OWT for empyema of various etiologies, employing a two-stage approach: intra-thoracic vacuum therapy followed by closure of the residual pleural space with a pedicled muscle flap. The outcomes demonstrate the feasibility and effectiveness of this technique in addressing complex OWT closure challenges and improving patient outcomes.
2025-12-31 | Erythrocyte photomodification in discrete plasmapheresis as a detoxification method in acute pleural empyema
Background. Acute pleural empyema is a severe disease accompanied by high systemic intoxication, metabolic disturbances, and purulent septic complications. Conventional therapy – antibiotics, pleural drainage, and infusions – may be insufficient due to accumulation of toxins and disruption of homeostasis. While extracorporeal methods such as plasmapheresis appear promising, classic approaches are limited by substantial losses of plasma proteins and immune components. Photomodification of erythrocytes may enhance detoxification and stimulate tissue repair processes. Aim. To assess the clinical efficacy, safety, and impact on tissue repair of three variants of detoxifying hemocorrection: Therapeutic Plasma Exchange (TPE), TPE with Partial Photomodification of Erythrocytes (TPE-PPE), and Small Volume TPE with Full Photomodification of Erythrocytes (SV-TPE-FPE) in patients with acute pleural empyema. Materials and Methods. A total of 105 patients with acute nonspecific pleural empyema treated at the Institute of General and Emergency Surgery (2008–2024) were enrolled. Patients were stratified into four groups: control (standard therapy), TPE, TPE-PPE, and SV-TPE-FPE. Apheresis procedures were performed every other day. Efficacy was monitored via clinical parameters (body temperature, duration of fever, severity of condition), complications, and morphological changes. Statistical analysis was carried out using variation statistics and Student's t-test, with Bonferroni correction for multiple comparisons. The study was carried out as a private initiative of the authors, without grant support or state registration of the topic. Research Ethics. The study was conducted in accordance with the principles of the World Medical Association Declaration of Helsinki (1964–2024) and approved by the Ethics Committee of the Educational and Scientific Medical Institute of National Technical University "Kharkiv Polytechnic Institute" (Protocol No.2 dated October 13, 2023). Written informed consent for the use of clinical data in scientific research was obtained from all patients, with adherence to the principles of confidentiality and voluntary participation. Results. The SV-TPE-FPE group demonstrated the best clinical dynamics: maximal body temperature decreased to 37.1°C, and the fever period was shortest (mean ≈ 18 days). The complication rate in this group was significantly lower than in other groups: fewer purulent septic complications and a reduced need for surgical interventions. No deaths were recorded in the SV-TPE-FPE group. Morphologically, there was the largest proportion of spontaneous scarring of pleural cavities in this group, suggesting activation of reparative processes. Conclusions. Small volume TPE with full photomodification of erythrocytes (SV-TPE-FPE) appears to be a promising method for treating acute pleural empyema, combining effective detoxification with activation of repair and reduced complication rates with no fatal outcomes in the studied sample. These findings support incorporating photomodified erythrocytes into comprehensive therapy, but further multicenter randomized studies are required to validate these results. Keywords: surgery, purulent diseases of the pleura, laboratory diagnostic.
proteins
2026-07-20 | Intrapleural Fibrinolytic Therapy in the Management of Pediatric Pleural Empyema: A Narrative Review
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. Conclusion: 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.
2026-06-19 | Intrapleural Fibrinolytics use in Children with Pleural Empyema: Safe and Effective.
We assessed the number of children with pleural empyema in which video assisted thoracoscopy (VATS) could be avoided in a center where standard therapy is drainage using a chest drain with/without intrapleural fibrinolytics. We included all children referred for chest drainage of a pleural effusion to RadboudUMC between 01-2022 and 04-2023. Children were referred in case of pneumonia with respiratory distress and suspected pleural effusion on the chest X-ray or an effusion size >20mm in the chest ultrasound, indicating the need for chest drainage or VATS. We analyzed symptoms, test results, and treatment. Thirty-three children aged 0-16 years were referred for treatment of pleural effusion. Most children presented with fever, cough and dyspnea (72%). Four children presented with abdominal pain (13%), which led to 2 appendectomies prior to referral. In 11 (33%) children an invasive group A streptococcus was cultured from the pleural fluid. All patients were treated with antibiotics. One patient received VATS primarily. 27 (84%) patients received a chest drain and four patients continued conservative treatment. 14 (52%) of the 27 children with a chest drain were treated with intrapleural fibrinolytics (alteplase or urokinase) because of persistent pleural effusion on ultrasound despite chest drainage. No side effects were observed. Two patients received VATS secondary to chest drainage without receiving prior intrapleural fibrinolytics. Intrapleural fibrinolytic treatment appeared safe and could avoid VATS in children with poor drainage and is therefore a useful minimal invasive treatment in children with pleural empyema.
2026-06-18 | The LTI-01-2001 phase 2a trial of intrapleural LTI-01 in patients with infected, non-draining pleural effusions.
Single chain urokinase (LTI-01) intrapleural enzymatic therapy (IET) was safe and promising in a phase 1 clinical trial to overcome failed drainage in patients with pleural infection. The LTI-01-2001 phase 2a trial was a randomized, double-blind, placebo-controlled, multi-center, dose-ranging study in hospitalized subjects with infected, non-draining pleural effusions. LTI-01, in doses of 400,000, 800,000 or 1,200,000 Units, or placebo was administered intrapleurally once daily for up to 3 days. The primary efficacy endpoint was incidence of treatment failure within 7 days of starting study medication. Treatment failure was defined as requiring alternative pleural therapy irrespective of subsequent treatment. Pleural opacification was a secondary endpoint and was assessed by CT imaging of the change in opacified area expressed as a percentage of the ipsilateral hemithorax (relative change) or absolute change in pleural opacification volume expressed in liters. 40/43 enrolled patients received LTI-01 or placebo due to constraints of the COVID-19 pandemic. There was no significant difference in incidence of treatment failure between the LTI-01 and placebo groups (OR 1.04, 95% CI 0.24,4.44, P = 0.96) while two predetermined sensitivity analyses demonstrated trends of improved efficacy in the 400,000 U group (P = 0.052 and 0.147). The absolute (Liters; L) and relative change from baseline in opacity volume were - 0.28 L (p=0.035) and - 55.8% (P = 0.064) versus placebo in the 800,000 U group, with significant reduction in absolute opacification found in the 400,000 and all LTI-01-treated groups combined (P < 0.03, respectively). There were no safety signals of concern, nor were there any episodes of intrapleural or pulmonary bleeding in LTI-01-treated patients. No statistically significant difference in the incidence of treatment failure was seen, potentially related to low recruitment. Trends towards efficacy were observed in predetermined sensitivity analyses at the 400,000 U dose of intrapleural LTI-01. Pleural opacification appeared most improved by the 800,000 U intrapleural LTI-01. A larger phase 2b trial is required to confirm these results or determine the efficacy of LTI-01 in patients with organizing, nondraining, infected pleural effusions. ClinicalTrials.gov NCT04159831. Registration date: November 12, 2019.
2026-05-25 | Extended Intrapleural Tissue Plasminogen Activator (tPA)-Dornase Alfa (DNase) Therapy Beyond the Standard Multicenter Intrapleural Sepsis Trial 2 (MIST-2) Regimen in a High-Risk Patient With Complex Empyema: A Case Report.
Pleural infection, including complicated parapneumonic effusion and empyema, remains a major management challenge, especially in patients who are poor surgical candidates. The Multicenter Intrapleural Sepsis Trial 2 (MIST-2) supports a six-dose regimen of intrapleural tissue plasminogen activator (tPA) plus dornase alfa (DNase), but the optimal duration of therapy in patients with persistent loculations remains uncertain. We describe a 62-year-old man with morbid obesity, New York Heart Association class III diastolic heart failure, and poorly controlled type 2 diabetes mellitus who presented with a complex, loculated left-sided empyema caused by Gemella sanguinis and Escherichia coli. Because of prohibitive operative risk, he was not considered a candidate for video-assisted thoracoscopic surgery. After incomplete improvement following the standard six-dose regimen, characterized by persistent fever, persistently elevated inflammatory markers, and residual loculations on repeat imaging, intrapleural therapy was extended for an additional six doses, for a total of 12 doses over six days. The patient had marked clinical and radiographic improvement, complete lung re-expansion, and no bleeding complications. This case suggests that, in carefully selected high-risk patients with persistent loculated empyema and no surgical option, extended intrapleural tPA-DNase therapy may be a feasible individualized strategy beyond the fixed MIST-2 protocol.
2026-04-23 | Pleural Infection as the First Presentation of a Large Retroperitoneal Abscess.
Empyema originating from a retroperitoneal source is rare due to the anatomical separation between the retroperitoneal and pleural spaces. We report the case of an 81-year-old man who presented with pleuritic chest pain following empirical antibiotic treatment for a urinary tract infection. Imaging revealed a large retroperitoneal gas-containing fluid collection and a left-sided loculated pleural effusion with a small pneumothorax. Pleural and retroperitoneal collection fluid both grew Escherichia coli suggestive of trans-diaphragmatic spread. A large hiatal hernia, structural defects of the hemidiaphragm and a Bochdalek hernia may also have been contributing factors. The patient improved with systemic antibiotics, percutaneous drainage of both collections and intrapleural administration of low dose tPA/DNase therapy. This case underscores the importance of considering extra-thoracic (especially abdominal) sources, especially in patients with structural diaphragmatic abnormalities.
small molecules
2026-08-07 | Pediatric pyopneumothorax caused by Prevotella oris successfully diagnosed via mNGS: a case report and literature review.
Empyema and pyopneumothorax are severe complications of pediatric community-acquired pneumonia. While typically caused by aerobic bacteria, anaerobic infections, particularly those involving Prevotella oris (P. oris), are exceedingly rare in children. This study aims to explore the clinical characteristics, diagnostic challenges, and therapeutic strategies for pediatric pyopneumothorax caused by P. oris, thereby enhancing clinical awareness of this uncommon opportunistic pathogen. We retrospectively analyzed the clinical data of a 10-year-old male admitted to the Hebei Children's Hospital in October 2025, presenting with acute chest pain and a history of tooth extraction 1 week prior to symptom onset. Radiological imaging revealed bilateral pneumonia with bilateral pleural effusions (predominantly on the left side). Pleural fluid analysis was consistent with an empyema. Traditional bacterial cultures of blood and pleural fluid yielded negative results. However, probe-based targeted metagenomic next-generation sequencing (mNGS) of the pleural fluid identified P. oris with a high relative abundance (81.86%), alongside other minor oral commensals. Based on the molecular diagnosis and the patient's ongoing clinical deterioration, cefoperazone-sulbactam was selected to strengthen coverage against anaerobic Gram-negative organisms, while linezolid was temporarily added to cover potential Gram-positive pleural co-infection during the acute deterioration phase. This was combined with closed thoracic drainage and intrapleural urokinase instillation for fibrinolysis, leading to a complete clinical recovery. Prevotella oris is a rare but significant pathogen in pediatric empyema. A high index of suspicion should be maintained for anaerobic infections in children presenting with a history of dental procedures, abnormal immune parameters or possible immunological vulnerability, or poor response to empirical antibiotics. Traditional cultures are often inadequate; therefore, mNGS serves as a crucial tool for the early detection and precise treatment of difficult-to-culture anaerobes.
2026-07-15 | Adult Empyema Caused by Refractory Methicillin-Resistant Staphylococcus aureus Treated Using Linezolid as Salvage Therapeutic Option: A Report of Two Cases.
The pathogenesis and treatment of pulmonary lesions caused by methicillin-resistant Staphylococcus aureus (MRSA) infection have been unclear because MRSA has usually been considered a colonizer. Two adult cases of MRSA empyema were treated using linezolid (LZD) because they were refractory to the glycopeptides vancomycin (VCM) and teicoplanin (TEIC). Case 1 was a 50-year-old man with a history of lung cancer and pneumothorax who was admitted with pulmonary empyema with a severe dry cough. MRSA empyema was diagnosed because only MRSA was detected by video-assisted thoracoscopy (VATS) from his effusions. He was initially treated using VCM for 10 days, but his inflammatory markers and condition did not so improve; therefore, VCM was switched to LZD. His condition improved with LZD for 14 days. Case 2 was a 77-year-old man with pharyngeal cancer who was admitted with respiratory failure. He was diagnosed with MRSA empyema because only MRSA was detected from his pleural effusions on pleural drainage. He received a TEIC drip infusion for 10 days, but his respiratory status did not so improve; therefore, his treatment was switched to LZD. His condition improved with LZD for 14 days. MRSA empyema was diagnosed in these two cases because only MRSA was detected from pleural effusions. Both patients finally improved following the switch from glycopeptide antibiotics to LZD. These findings suggest MRSA as the true cause of the infections and that LZD, rather than VCM and TEIC, might be effective in cases of MRSA empyema.
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.
antibodies
2025-08-18 | The role of interleukin-6 signalling in pleural infection: observational and genetic analyses.
Pleural infection is associated with marked local and systemic inflammation leading to significant morbidity. It may be possible to therapeutically augment this response and interleukin-6 is a key signalling cascade in inflammatory pathologies. We performed a prospective observational study recruiting patients with pleural effusions secondary to infection and measured interleukin-6 in matched pleural fluid and serum (n = 76). We subsequently performed a large-scale, two sample Mendelian Randomisation study (1601 cases and 830,709 controls), using genetic variation at IL6R to proxy the effect of interleukin-6 inhibition on pleural infection and overcome confounding inherent in observational analyses. Pleural interleukin-6 levels in infection were 5000-fold higher than matched serum levels (median 72,752 pg/ml vs. 15 pg/ml). Pleural interleukin-6 predicted systemic inflammation (neutrophil count, C- reactive protein), correlated with clinical markers of disease severity (effusion size, pH, glucose), and was strongly associated with length of hospital stay. In Mendelian randomisation analyses, interleukin-6 inhibition was predicted to have a large protective effect on the incidence of infection (OR 0.23; 95% CI 0.14-0.39 per standard deviation decrease in C- reactive protein). The effect size was larger than that seen in COVID-19 and coronary artery disease, where interleukin-6 inhibition has been successful in trials. Multiple lines of evidence suggest pleural interleukin-6 drives pathology in pleural infection. Targeting interleukin-6 may hold promise and should be considered in randomised trials. This study has been funded by the National Institutes of Health and Care Research Bristol Biomedical Research Centre.
2024-12-20 | IMMUNOLOGICAL DISORDERS IN PLEURAL EMPYEMA AND THE POSSIBILITY OF THEIR CORRECTION
Abstract. Problems in the treatment of acute pleural empyema are caused by a number of objective and subjective reasons, in particular, such as the widespread spread of antibiotic-resistant microflora and allergization of the population. Literature data indicate the need to improve immunostimulating therapy in patients with pleural empyema. A study of the long-term results of all types of treatment for this pathology shows that they do not give 100% success. The presented data indicate the need to improve immunostimulating therapy in patients with pleural empyema.
2020-10-05 | Precision Targeting of the Plasminogen Activator Inhibitor-1 Mechanism Increases Efficacy of Fibrinolytic Therapy in Empyema
Abstract Plasminogen activator inhibitor-1 (PAI-1) is an endogenous irreversible inhibitor of tissue-type (tPA) and urokinase (uPA) plasminogen activators. PAI-1-targeted fibrinolytic therapy (PAI-1-TFT) is designed to decrease the therapeutic dose of tPA and uPA to attenuate the risk of bleeding and other complications. The docking site peptide (DSP) is a part of the PAI-1 reactive center loop, which interacts with plasminogen activators, thus affecting the PAI-1 mechanism. We used DSP for PAI-1-TFT in two rabbit models: chemically-induced pleural injury and Streptococcus pneumoniae induced empyema. PAI-1-TFT with DSP combined with single chain uPA or tPA resulted in an up to 8-fold decrease in the minimal effective therapeutic dose of plasminogen activator and induced no bleeding. An increase in the level of PAI-1 in infectious pleural injury, when compared to chemically-induced injury, coincided with an increase in the minimal effective dose of plasminogen activator and DSP. PAI-1 is a valid molecular target in S. pneumoniae empyema model in rabbits, which closely recapitulates key characteristics of empyema in humans. Low dose PAI-1-TFT is a novel precise interventional strategy that may improve fibrinolytic therapy of empyema in clinical practice.
2015-07-07 | Salmonella Enteritidis Empyema Preceding the Diagnosis of Non-Hodgkin’s Lymphoma and Subsequent Contralateral Chylothorax Treated with Radiolabelled Rituximab
Salmonella infection is common, but pleural involvement has rarely been reported.Only seven cases of Salmonella enteritidis pleural empyema have been reported; all had an associated preexisting underlying immunosuppresion or malignancy.We report the case of an apparently healthy man who developed S. enteritidis empyema.On further follow-up and surveillance, he eventually presented with non-Hodgkin's lymphoma and a contralateral recurrent chylothorax.The latter was successfully controlled with radiolabeled rituximab, which has never been described for the above purpose in literature before.
2015-05-22 | Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.
A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.
cell therapies
2026-08-12 | Role of omental flaps in thoracic surgery complications: a narrative review.
The greater omentum is a highly vascularized and immunologically active organ with recognized regenerative and antimicrobial properties. Its application in pleural space complications has gained renewed interest with the expansion of minimally invasive harvesting techniques. This review summarizes the current literature regarding the role of omental flaps in the management of post-lobectomy complications. This narrative review was conducted using a comprehensive search of MEDLINE (Via PubMed), Scopus, and Cochrane Central Register of Controlled Trials from database inception through February 2026 using the search terms "Omental flap", "pleural space", and "bronchopleural fistula", "post-lobectomy complications", "entrapped lung" and "empyema". Peer-reviewed articles in English and Spanish were included. Data were extracted and synthesized narratively, focusing on indications, techniques, outcomes, advantages, and limitations. Omental flaps are most used for bronchopleural fistula (BPF), empyema, mediastinitis, and prosthetic graft coverage. Rich vascular and lymphatic networks of the omentum enhance infection control and tissue healing, particularly in contaminated or high-risk fields. The size and pliability of the omentum allow effective obliteration of complex pleural dead space problems and durable coverage of critical structures. Reported flap survival rates range from 80-100% in small case series. Omental flaps represent a versatile and biologically advantageous option for pleural space complications. Although current evidence is limited and largely observational, reported outcomes are promising, warranting further prospective investigation.
2026-06-04 | Surgical management of recurrent MRSA empyema with eloesser flap in a complex thoracic patient: lessons from endobronchial valve failure.
Endobronchial valves (EBVs) have emerged as a minimally invasive option for managing bronchopleural fistula (BPF), with reported efficacy rates of approximately 70-75%. However, their long-term performance in the setting of chronic infection remains poorly characterized, and documentation of specific failure mechanisms is limited. A 74-year-old man with recurrent methicillin-resistant Staphylococcus aureus (MRSA) empyema following right lower lobectomy presented with treatment failure 14 months after Zephyr EBV placement. During Eloesser flap creation, both valves were found displaced from the bronchial stump, with one completely dislodged into the pleural space. The bronchial stump showed evidence of erosion from chronic infection. The patient demonstrated clinical improvement following the Eloesser procedure, with negative cultures at three-month follow-up. This case provides direct intraoperative visualization of EBV displacement in chronic empyema, suggesting that ongoing infection, tissue destruction, and mechanical forces may compromise valve stability over time. The finding supports consideration of patient selection criteria for EBV therapy and demonstrates the continued role of open drainage procedures when minimally invasive approaches fail.
2026-04-04 | Single-stage open window thoracostomy with simultaneous muscle flap transposition and early negative pressure wound therapy for chronic empyema: a propensity score- and machine learning-based study.
BACKGROUND: To compare the clinical efficacy of a single-stage surgical approach combining open window thoracostomy, muscle flap transposition, and early negative pressure wound therapy (NPWT) with that of conventional staged management for chronic empyema. METHODS: This retrospective, single-center cohort included 45 patients with chronic empyema (single-stage, n = 7; conventional, n = 38) who were treated from 2009 to 2024. The primary endpoint was the cavity reduction ratio measured via three-dimensional computed tomography (3D CT). To minimize selection bias, we applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). We prespecified the average treatment effect on the treated (ATT) as the primary estimand, whereas the average treatment effect (ATE) was considered exploratory because treatment assignment was strongly related to bronchopleural fistula (all single-stage patients had BPF) and overlap was limited. The follow-up intervals were linearly normalized to adjust for time-dependent variability. Machine learning models were used as complementary predictive analyses to identify predictors of cavity reduction. RESULTS: After PSM (n = 5 per group), the single-stage group had significantly greater cavity reduction than the conventional group did (90% [89–94%] vs. 37% [32–43%], p = 0.008). The IPTW analysis demonstrated significant treatment effects: 0.38 (95% CI: 0.17–0.59, p = 0.005) for the ATT and 0.63 (95% CI: 0.12–1.14, p = 0.03) for the ATE (exploratory). Machine learning models consistently identified the treatment approach and time-related variables as important predictors of cavity reduction. CONCLUSIONS: Compared with conventional management, the single-stage approach was associated with significantly greater empyema cavity reduction and was feasible even in patients with bronchopleural fistulas. Causal interpretation is most defensible for the ATT, whereas generalization to the full population (ATE) should be considered exploratory due to limited overlap. Despite the small sample size, the consistent findings across diverse analytical frameworks support the single-stage strategy as a promising approach that warrants prospective multicenter validation and clearer criteria for patient selection.
2026-02-12 | An alternative method of closure of open window thoracostomy: a two-staged approach.
Refractory empyema poses significant treatment challenges, but open window thoracostomy (OWT) remains an effective solution, facilitating infection control and promoting recovery. However, after the resolution of infection, patients often face complications due to the open pleural cavity and residual pleural space. The closure of open window thoracostomies is particularly difficult, especially in the presence of large residual spaces and bronchopleural fistulas (BPFs). This case series examines six patients who underwent OWT for empyema of various etiologies, employing a two-stage approach: intra-thoracic vacuum therapy followed by closure of the residual pleural space with a pedicled muscle flap. The outcomes demonstrate the feasibility and effectiveness of this technique in addressing complex OWT closure challenges and improving patient outcomes.
2025-12-31 | Erythrocyte photomodification in discrete plasmapheresis as a detoxification method in acute pleural empyema
Background. Acute pleural empyema is a severe disease accompanied by high systemic intoxication, metabolic disturbances, and purulent septic complications. Conventional therapy – antibiotics, pleural drainage, and infusions – may be insufficient due to accumulation of toxins and disruption of homeostasis. While extracorporeal methods such as plasmapheresis appear promising, classic approaches are limited by substantial losses of plasma proteins and immune components. Photomodification of erythrocytes may enhance detoxification and stimulate tissue repair processes. Aim. To assess the clinical efficacy, safety, and impact on tissue repair of three variants of detoxifying hemocorrection: Therapeutic Plasma Exchange (TPE), TPE with Partial Photomodification of Erythrocytes (TPE-PPE), and Small Volume TPE with Full Photomodification of Erythrocytes (SV-TPE-FPE) in patients with acute pleural empyema. Materials and Methods. A total of 105 patients with acute nonspecific pleural empyema treated at the Institute of General and Emergency Surgery (2008–2024) were enrolled. Patients were stratified into four groups: control (standard therapy), TPE, TPE-PPE, and SV-TPE-FPE. Apheresis procedures were performed every other day. Efficacy was monitored via clinical parameters (body temperature, duration of fever, severity of condition), complications, and morphological changes. Statistical analysis was carried out using variation statistics and Student's t-test, with Bonferroni correction for multiple comparisons. The study was carried out as a private initiative of the authors, without grant support or state registration of the topic. Research Ethics. The study was conducted in accordance with the principles of the World Medical Association Declaration of Helsinki (1964–2024) and approved by the Ethics Committee of the Educational and Scientific Medical Institute of National Technical University "Kharkiv Polytechnic Institute" (Protocol No.2 dated October 13, 2023). Written informed consent for the use of clinical data in scientific research was obtained from all patients, with adherence to the principles of confidentiality and voluntary participation. Results. The SV-TPE-FPE group demonstrated the best clinical dynamics: maximal body temperature decreased to 37.1°C, and the fever period was shortest (mean ≈ 18 days). The complication rate in this group was significantly lower than in other groups: fewer purulent septic complications and a reduced need for surgical interventions. No deaths were recorded in the SV-TPE-FPE group. Morphologically, there was the largest proportion of spontaneous scarring of pleural cavities in this group, suggesting activation of reparative processes. Conclusions. Small volume TPE with full photomodification of erythrocytes (SV-TPE-FPE) appears to be a promising method for treating acute pleural empyema, combining effective detoxification with activation of repair and reduced complication rates with no fatal outcomes in the studied sample. These findings support incorporating photomodified erythrocytes into comprehensive therapy, but further multicenter randomized studies are required to validate these results. Keywords: surgery, purulent diseases of the pleura, laboratory diagnostic.
proteins
2026-07-20 | Intrapleural Fibrinolytic Therapy in the Management of Pediatric Pleural Empyema: A Narrative Review
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. Conclusion: 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.
2026-06-19 | Intrapleural Fibrinolytics use in Children with Pleural Empyema: Safe and Effective.
We assessed the number of children with pleural empyema in which video assisted thoracoscopy (VATS) could be avoided in a center where standard therapy is drainage using a chest drain with/without intrapleural fibrinolytics. We included all children referred for chest drainage of a pleural effusion to RadboudUMC between 01-2022 and 04-2023. Children were referred in case of pneumonia with respiratory distress and suspected pleural effusion on the chest X-ray or an effusion size >20mm in the chest ultrasound, indicating the need for chest drainage or VATS. We analyzed symptoms, test results, and treatment. Thirty-three children aged 0-16 years were referred for treatment of pleural effusion. Most children presented with fever, cough and dyspnea (72%). Four children presented with abdominal pain (13%), which led to 2 appendectomies prior to referral. In 11 (33%) children an invasive group A streptococcus was cultured from the pleural fluid. All patients were treated with antibiotics. One patient received VATS primarily. 27 (84%) patients received a chest drain and four patients continued conservative treatment. 14 (52%) of the 27 children with a chest drain were treated with intrapleural fibrinolytics (alteplase or urokinase) because of persistent pleural effusion on ultrasound despite chest drainage. No side effects were observed. Two patients received VATS secondary to chest drainage without receiving prior intrapleural fibrinolytics. Intrapleural fibrinolytic treatment appeared safe and could avoid VATS in children with poor drainage and is therefore a useful minimal invasive treatment in children with pleural empyema.
2026-06-18 | The LTI-01-2001 phase 2a trial of intrapleural LTI-01 in patients with infected, non-draining pleural effusions.
Single chain urokinase (LTI-01) intrapleural enzymatic therapy (IET) was safe and promising in a phase 1 clinical trial to overcome failed drainage in patients with pleural infection. The LTI-01-2001 phase 2a trial was a randomized, double-blind, placebo-controlled, multi-center, dose-ranging study in hospitalized subjects with infected, non-draining pleural effusions. LTI-01, in doses of 400,000, 800,000 or 1,200,000 Units, or placebo was administered intrapleurally once daily for up to 3 days. The primary efficacy endpoint was incidence of treatment failure within 7 days of starting study medication. Treatment failure was defined as requiring alternative pleural therapy irrespective of subsequent treatment. Pleural opacification was a secondary endpoint and was assessed by CT imaging of the change in opacified area expressed as a percentage of the ipsilateral hemithorax (relative change) or absolute change in pleural opacification volume expressed in liters. 40/43 enrolled patients received LTI-01 or placebo due to constraints of the COVID-19 pandemic. There was no significant difference in incidence of treatment failure between the LTI-01 and placebo groups (OR 1.04, 95% CI 0.24,4.44, P = 0.96) while two predetermined sensitivity analyses demonstrated trends of improved efficacy in the 400,000 U group (P = 0.052 and 0.147). The absolute (Liters; L) and relative change from baseline in opacity volume were - 0.28 L (p=0.035) and - 55.8% (P = 0.064) versus placebo in the 800,000 U group, with significant reduction in absolute opacification found in the 400,000 and all LTI-01-treated groups combined (P < 0.03, respectively). There were no safety signals of concern, nor were there any episodes of intrapleural or pulmonary bleeding in LTI-01-treated patients. No statistically significant difference in the incidence of treatment failure was seen, potentially related to low recruitment. Trends towards efficacy were observed in predetermined sensitivity analyses at the 400,000 U dose of intrapleural LTI-01. Pleural opacification appeared most improved by the 800,000 U intrapleural LTI-01. A larger phase 2b trial is required to confirm these results or determine the efficacy of LTI-01 in patients with organizing, nondraining, infected pleural effusions. ClinicalTrials.gov NCT04159831. Registration date: November 12, 2019.
2026-05-25 | Extended Intrapleural Tissue Plasminogen Activator (tPA)-Dornase Alfa (DNase) Therapy Beyond the Standard Multicenter Intrapleural Sepsis Trial 2 (MIST-2) Regimen in a High-Risk Patient With Complex Empyema: A Case Report.
Pleural infection, including complicated parapneumonic effusion and empyema, remains a major management challenge, especially in patients who are poor surgical candidates. The Multicenter Intrapleural Sepsis Trial 2 (MIST-2) supports a six-dose regimen of intrapleural tissue plasminogen activator (tPA) plus dornase alfa (DNase), but the optimal duration of therapy in patients with persistent loculations remains uncertain. We describe a 62-year-old man with morbid obesity, New York Heart Association class III diastolic heart failure, and poorly controlled type 2 diabetes mellitus who presented with a complex, loculated left-sided empyema caused by Gemella sanguinis and Escherichia coli. Because of prohibitive operative risk, he was not considered a candidate for video-assisted thoracoscopic surgery. After incomplete improvement following the standard six-dose regimen, characterized by persistent fever, persistently elevated inflammatory markers, and residual loculations on repeat imaging, intrapleural therapy was extended for an additional six doses, for a total of 12 doses over six days. The patient had marked clinical and radiographic improvement, complete lung re-expansion, and no bleeding complications. This case suggests that, in carefully selected high-risk patients with persistent loculated empyema and no surgical option, extended intrapleural tPA-DNase therapy may be a feasible individualized strategy beyond the fixed MIST-2 protocol.
2026-04-23 | Pleural Infection as the First Presentation of a Large Retroperitoneal Abscess.
Empyema originating from a retroperitoneal source is rare due to the anatomical separation between the retroperitoneal and pleural spaces. We report the case of an 81-year-old man who presented with pleuritic chest pain following empirical antibiotic treatment for a urinary tract infection. Imaging revealed a large retroperitoneal gas-containing fluid collection and a left-sided loculated pleural effusion with a small pneumothorax. Pleural and retroperitoneal collection fluid both grew Escherichia coli suggestive of trans-diaphragmatic spread. A large hiatal hernia, structural defects of the hemidiaphragm and a Bochdalek hernia may also have been contributing factors. The patient improved with systemic antibiotics, percutaneous drainage of both collections and intrapleural administration of low dose tPA/DNase therapy. This case underscores the importance of considering extra-thoracic (especially abdominal) sources, especially in patients with structural diaphragmatic abnormalities.
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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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