Materiały źródłowe

• #1 Thoracic Empyema – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544279/

  Thoracic empyema, characterized by the presence of purulent fluid in the pleural space, remains a significant clinical challenge with considerable morbidity and mortality. This condition typically arises as a complication of pneumonia, chest trauma, or surgery and is associated with the complex pathophysiologic processes of infection and inflammation. […] The development of pleural space infections likely involves increased permeability of the mesothelial layer of the inflamed pleurae, allowing bacteria to invade the typically sterile space. […] Approximately 60 years ago, the American Thoracic Society first described the evolution of empyema as a continuous process subdivided into 3 distinct but continuous stages or phases: exudative, fibrinopurulent and loculated, and chronic organizational. Specific pleural fluid characteristics, radiographic findings, and corresponding treatments distinguish these stages of parapneumonic effusion, pleural infection, and empyema.

• #1 Thoracic Empyema – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544279/

  The initial phase of empyema formation is an exudative effusion, where fluid rapidly accumulates in the pleural space. During this phase, pleural fluid is typically culture and Gram stain negative, with glucose levels exceeding 60 mg/dL and lactate dehydrogenase (LDH) levels less than 3 times the upper limit of normal for serum. Proinflammatory mediators like tumor necrosis factor-alpha (TNF-), interleukin 6 (IL-6), and IL-8 are believed to be vital in driving the inflammatory response at this stage. […] The second phase is the fibrinopurulent stage, which follows the initial exudative phase and typically results if antibiotic treatment is inadequate or delayed. This phase is characterized by bacterial invasion into the pleural space. In this stage, the pleural fluid will generally have a glucose level below 60 mg/mL with a pH below 7.20 and a pleural fluid LDH greater than 3 times the upper limit of normal for serum. Increased plasminogen-activator inhibitors and TNF- lead to fibrin deposition, which forms septations and loculations.

• #1 Thoracic Empyema – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544279/

  The final stage, known as the organizing phase, is marked by the growth of fibroblasts into the visceral and parietal pleurae. This is accompanied by the deposition of a collagen-rich fibrin matrix within the pleural space, resulting in pleural thickening. This phase often leads to developing an inelastic visceral pleural peel, which can cause lung entrapment. The proliferation of fibroblasts is believed to be driven by the release of transforming growth factor-beta and platelet-derived growth factor.

• #2 Empyema: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/24269-empyema

  Empyema typically develops when an infection spreads from your lungs to the pleural space. […] The most common cause of empyema is pneumonia. Other causes include: Tuberculosis, Lung abscess, Chest surgery, Chest injuries or trauma. […] Empyema is an infection in which pus develops in your pleural space. […] Without proper treatment, empyema can get worse and may be fatal. […] Yes, there’s a cure for empyema. Treatment includes removing pus from your pleural space and treating the infection, usually with antibiotics. […] A provider will remove pus through thoracentesis in the early stages of empyema. […] In the later stages of empyema, a provider may need to perform a more invasive procedure, such as surgically removing fibrous tissue (decortication), a thoracotomy or a video-assisted thoracic surgery (VATS).

• #2 Empyema: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/24269-empyema

  Empyema isn’t common. Most cases don’t progress to later stages with early treatment. However, it can be fatal without proper treatment in 5% to 30% of people with empyema and other conditions (comorbidities). The mortality rate is about 40% in immunocompromised people who have empyema. […] Empyema is a condition in which you have pus in your pleural space. It usually causes symptoms that affect your chest and breathing. Though it’s not common, if a healthcare provider diagnoses empyema early, your chances of making a full recovery are good. However, empyema can be fatal if you don’t receive treatment or have other conditions.

• #3 Parapneumonic Pleural Effusions and Empyema Thoracis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534297/

  A parapneumonic effusion refers to the accumulation of exudative pleural fluid associated with an ipsilateral lung infection, mainly pneumonia. Parapneumonic effusions are mainly associated with bacterial infections. […] Empyema thoracis in which there is frank pus in the pleural space, or there is evidence of bacterial infection of the pleural fluid by Gram stain or a positive culture. […] Pneumonia is the most frequent cause of parapneumonic effusions and empyema thoracis. Empyema may result as a complication of cardiothoracic surgery. Trauma can also lead to infection of the pleural space. The infecting organism may have spread from blood or other organs into the pleural space. […] Both viruses and bacteria can cause parapneumonic effusions, but it is the latter that is the most common cause of empyema thoracis.

• #3 Parapneumonic Pleural Effusions and Empyema Thoracis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534297/

  The stages of parapneumonic effusion are: Exudative stage, in which there is an accumulation of fluid in the pleural space due to increased capillary permeability that results from proinflammatory cytokines, such as interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-a). The pleural fluid in this early stage is usually clear exudative fluid with a predominance of neutrophils. […] Fibrinopurulent stage, which can develop if adequate treatment is not provided. In this stage there is a deposition of fibrin clots and fibrin membranes in the pleural cavity, leading to fluid loculations. […] Organizing stage, in which fibrin membranes are transformed by fibroblast into a thick nonelastic pleural peel, resulting in the trapped lung with restrictive respiratory dysfunction. […] The clinical course varies from spontaneous healing to chronic empyema and fibro-thorax with trapped restricted lung.

• #4 Pleural empyema pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pleural_empyema_pathophysiology

  The process leading to the formation of empyema involves migration of organisms into the pleural cavity. Lung parenchymal infection stimulates local pleural immune activation, neutrophil migration and release of inflammatory cellular components and toxic oxygen species, such as IL-6, IL-8 and tumour necrosis factor (TNF)-. These mediators promotes endothelial injury resulting in increased pleural membrane permeability and increased osmotic pressure. The resultant empyema may spontaneously burrowed through the parietal pleura into the chest wall to form a subcutaneous abscess that may eventually rupture through the skin leading to formation of empyema necessitans. Mesothelial cells release TNF- and concurrently antifibrinolytic mediator function is enhance, example plasminogen activator inhibitor-1 and -2.

• #4 Pleural empyema pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pleural_empyema_pathophysiology

  Mycobacteria bacille CalmetteGuerin infection of pleural cells lead to enhanced VEGF release. Mycobacteria bacille CalmetteGuerin (BCG) and S. aureus infections increase permeability across the mesothelial membrane, partly via downregulation of -catenin. […] With persistent inflammation, increased permeability of vascular and mesothelial membranes results in increased plasma leakage into the pleural cavity. Coagulation cascade when activated within the pleural cavity contributes to the development of a fibrinopurulent or complicated parapneumonic effusion. Fibrin is deposited over the pleural surfaces with fibrinous septae producing loculated effusions.

• #5 Pneumonia and empyema: causal, casual or unknown – McCauley – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4297/4847

  Parapneumonic effusions arise from inflammation in the lungs and pleural space from direct invasion of bacteria, cascade of inflammatory events and bacteriologic virulence features. […] The evolution of parapneumonic effusion can be divided into three progressive stages: (I) exudative stage; (II) fibrinopurulent stage; and (III) organizing stage with pleural peel formation. […] The most common cause of increased pleural fluid formation is increased interstitial edema. This can occur as a result of several processes and is the predominant mechanism for the formation of parapneumonic effusions along with pleural effusions related to congestive heart failure (CHF), pulmonary embolism and acute respiratory distress syndrome. […] The evolution of parapneumonic effusion is divided into three progressive stages: (I) exudative stage; (II) fibrinopurulent stage; and (III) organizing stage with pleural peel formation.

• #5 Pneumonia and empyema: causal, casual or unknown – McCauley – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4297/4847

  In the early exudative stage there is a rapid outpouring of fluid and inflammatory cells into the pleural space due to increased capillary microvascular permeability. […] This invasion accelerates the immune response and directly contributes to fluid loculation by promoting further migration of neutrophils and activation of the coagulation cascade. […] The pleural fluid in the fibrinopurulent stage is often turbid and characterized by positive bacteria on Gram stain and culture. […] If stage 2 pleural fluid is not drained in conjunction with effective antibiotic therapy, the effusion may progress to stage 3, the organizing stage. […] This final stage is characterized by fibroblasts that proliferate and invade the pleural fluid from both the visceral and parietal pleura, forming a thick pleural peel.

• #6 Empyema | Thoracic Key

  https://thoracickey.com/empyema-2/

  Most empyemas are the result of bacterial suppuration in organs that are contiguous with the pleural surface. Among these, the lungs are the most common source. In such cases, empyema occurs by direct bacterial spread across the visceral pleura or by free intrapleural rupture of microscopic and peripherally located lung abscesses. […] In most series, empyemas are secondary to bronchopulmonary infections in 50% to 60% of cases and nearly all of the so-called primary empyemas result from subclinical pneumonic processes. […] Inactive pulmonary tuberculosis, diabetes mellitus, long-term steroid therapy, and various malignancies are other common predisposing conditions. […] These may lead to parenchymal destruction with subsequent contamination of the pleural space, which results in either simple empyema or complex infections including bronchopleural fistula.

• #7

  https://www.lumen.luc.edu/lumen/meded/medicine/pulmonar/diseases/pul15.htm

  Empyema most often is due to extension of infection from pneumonia. Staphylococcal, gram negative and anaerobic infections are common infections presenting in this mode. […] Anaerobic infections can seed pleura and start as the primary site of infection without a preceding pneumonitis. […] It could also follow contamination of pleural space from non-sterile pleural taps.

• #8

  https://link.springer.com/article/10.1007/s00068-002-1264-2

  Posttraumatic empyema remains a significant clinical problem occurring in 210% of victims with thoracic trauma. […] The primary feature associated with posttraumatic empyema is a retained hemothorax following chest trauma. Blood trapped within the pleural space impairs its own absorption and acts as an ideal culture medium for bacterial proliferation. Contamination of a retained hemothorax is derived from several sources, including tube thoracostomy, pneumonia, or from the mechanism of injury itself. The combination of tube thoracostomy and retained blood within the pleural space is implicated in most cases of posttraumatic empyema.

• #9 Empyema: ED Presentation, Evaluation, and Management – emDocs

  https://www.emdocs.net/empyema-ed-presentation-evaluation-and-management/

  Empyema refers to a collection of pus within the pleural space. This can be caused by bacteria, fungi, parasites, or mycobacteria because of adjacent pneumonia, direct inoculation (blunt trauma/prior chest tube), or other source. […] Patients hospitalized with pneumonia are at greatest risk, with one study showing that 20-40% of admitted pneumonia have/develop a parapneumonic effusion with 5-10% of these cases developing empyema. […] As one would expect, pneumonia is a large risk factor for developing an empyema. Therefore, there is much overlap between the risk factors for developing pneumonia and empyema. […] Patients with empyema usually present with symptoms similar to that of pneumonia. These include fever, dyspnea, cough, increased sputum production, and pleuritic chest pain. […] In order to diagnose an empyema, one needs to be able to see inside the chest.

• #10 Empyema | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/respiratory-intensive-care/Chapter-11/empyema

  About 90% will do this, and the remaining 10% will progress to become an empyema, according to Strange & Sahn, 1999. […] When one hears „empyema”, one typically lunges for the antibiotics, but in fact it appears that there may be causes that are not ostensibly infectious, and there are mentions in the literature of empyemas which are due to inflammatory noninfectious causes. […] This is from a table in Addala et al (2021). Additionally, Dyrhovden et al (2019) lists a selection of organisms which were found unexpectedly and which are mostly of periodontal origin (eg. Fusobacterium nucleatum and Streptococcus intermedius), presumably spread there haematogenously. […] The most important features of which will be useful to determine 1) why did this happen, 2) what is the most likely organism, and 3) the natural history.

• #10 Empyema | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/respiratory-intensive-care/Chapter-11/empyema

  Risk factors for developing a post-pneumonia empyema: Diabetes, Alcohol use, Drug addiction, Malnutrition. […] Risk factors for a random empyema out of the blue: Poor dentition, Aspiration pneumonia, Malignancy, Haemothorax, eg. following frequent falls or chest surgery (if left undrained, the risk is something like 26.8% in one study by DuBose et al, 2012). […] Recent hospital stay (hospital-acquired empyema is more likely to develop into a complicated loculated collection). […] It probably goes without saying that antibiotic therapy is essential irrespective of which drainage option one picks, and the duration of treatment increases by 1-2 weeks with each evolving stage of empyema, such that the uncomplicated parapneumonic effusion scarcely needs more antibiotics than the pneumonia that caused it, whereas a loculated organising empyema requires at least six weeks if not more.

• #10 Empyema | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/respiratory-intensive-care/Chapter-11/empyema

  Either way, the purulent pleural collection progresses through some predictable stages, the classification of which was created in the 1960s: Stage 1. Simple exudate. It is just an exudate with a decent amount of neutrophils in it, in other words pus. […] Stage 2. Fibrinopurulent stage. It is pus, but heterogeneous in texture, and clearly infected (positive gram stain, etc). […] Stage 3. Organising stage. It is developing into loculations, with potentially rather diverse conditions in each pocket. […] These classifications remain relevant since the mid-20th century because each stage has slightly different management options available. […] How is it not just a pleural effusion of some benign cause? […] An uncomplicated parapneumonic effusion (i.e. one which is exudative but not infected) will likely have none of these features, and will usually resolve with antibiotics alone (i.e. the effusion goes away with the pneumonia).

• #10 Empyema | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/respiratory-intensive-care/Chapter-11/empyema

  If the septae are mostly fibrin, then it stands to reason that fibrinolytic agents should be able to destroy them. […] This is the rationale for injecting agents typically reserved for IV thrombolysis into the pleural cavity. […] The outcome from this and several other trials had demonstrated a trend towards faster resolution and less frequent need for surgery.

• #11 {courseTitle}

  https://www.abdn.ac.uk/medical/elf/courses/view/144761/thoracic-empyema/1/page5

  The commonest reason for empyema development is spread of infection from associated community acquired pneumonia (parapneumonic empyema). […] The organism usually responsible is Streptococcus pneumoniae. […] Parapneumonic empyema develops as a result of transpleural bacterial translocation into a previously sterile pleural effusion or as a result of rupture of lung abscess into the pleural cavity. […] Chest trauma is the next commonest cause of empyema, usually blunt trauma in the UK, but often penetrating trauma in other parts of the world. […] In penetrating chest trauma, the infection is often caused by gram negative gut bacteria, as penetrating chest injuries are often transdiaphragmatic in extent. […] In blunt chest trauma, haemothorax is superinfected as a result of co-incident hypostatic pneumonia, haematogenously or as a result of ascending infection on chest drains that have to be left in place for long periods of time.

• #12 Empyema | Diagnosis & Disease Information – Pulmonology Advisor

  https://www.pulmonologyadvisor.com/ddi/empyema/

  Defined as a collection of pus in the thoracic cavity arising from infection in the pleural space, empyema is most commonly caused by bacterial pneumonia and the resulting accumulation of fluid (parapneumonic effusion) in the pleural space. […] The development of empyema as a result of pleural infection occurs in 3 stages: Exudative stage (stage I): a small amount of sterile fluid is accumulated in the pleural space following acute inflammatory response; Fibropurulent stage (stage II): increased neutrophil counts and fibrin deposition due to an infection and collection of pleural fluid in loculated segments; Organized stage (stage III): fibrin deposits and production of a thick pleural peel lead to restricted lung expansion and chronic empyema. […] Once empyema progresses to the transitional fibropurulent stage with multiple loculations, tube thoracostomy drainage is usually not sufficient for complete drainage. In addition to thoracostomy, fibrinolytic agents which induce lysis of fibrin deposits have been used to improve drainage. […] Surgical treatment options for advanced-stage empyema consist of VATS or pleural decortication, in which excision of the thick fibrous peel from the pleural surface restores lung re-expansion.

• #13 Pediatric Empyema: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1001747-overview

  In stage 1, the exudative stage, the pleural inflammation from a contiguous infection results in increased permeability and a small fluid collection. At this stage, the effusion is thin and amenable to thoracentesis alone, contains neutrophils, has normal pH and glucose levels, and is often sterile. Stage 2, the fibrinopurulent stage, is characterized by invasion of the organism into the pleural space, progressive inflammation, and significant polymorphonuclear (PMN) leukocyte invasion. The increase in fibrin deposition also results in partitions or loculations within the pleural space. Inflammation is characterized by progressive decreases in the pleural fluid glucose and pH levels and increased protein and lactate dehydrogenase (LDH) levels. The last stage, stage 3, is the organizing stage, in which a pleural peel is created by the resorption of fluid and is associated with fibroblast proliferation that can result in parenchymal entrapment.

• #13 Pediatric Empyema: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1001747-overview

  Activation of the coagulation cascade is common with pleural empyema. The pleural inflammatory response favors increased procoagulant activity, as well as depressed fibrinolytic activity, which favors fibrin deposition. Loculations result with these fibrin strands covered rapidly by a meshwork of fibroblasts that both proliferate and deposit basement membrane proteins onto the surface of the pleura. These proteins obscure the separation of the visceral and parietal pleura and lead to the formation of the pleural peel. […] Following initiation of appropriate therapy, the inflammatory cellular and cytokine production recedes, and the PMN predominance of the parapneumonic effusion decreases. An influx of macrophages assists in the clearance of PMNs, with resolution of the inflammatory process. Migration of pleural mesothelial cells into areas of denuded mesothelium results in the reepithelialization of the pleura and recovery of normal function; however, following exuberant pleural inflammation, the potential for pleural fibrosis and restrictive lung disease is enhanced. The mechanisms that lead to either the development of pleural fibrosis or pleural repair with normal recovery are not well understood and need further investigation and characterization.

• #13 Pediatric Empyema: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1001747-overview

  Bacterial pneumonia with associated pleural empyema is the most common cause of pleural effusion found in the pediatric population. Parapneumonic effusions are predominately exudative and occur in as many as 50-70% of patients admitted with a complicated pneumonia. […] The pulmonary infections of these patients extend into the pleural space and require more extensive therapy, with associated increased morbidity and extended hospital stay. Involvement of the pleural space with pulmonary infections has been recognized since ancient times. […] The definition of a parapneumonic effusion is a pleural effusion associated with either bacterial pneumonia or lung abscess or, rarely, external introduction of organisms associated with chest wall trauma. The development of parapneumonic effusions is gradual, with the pleural fluid collection most commonly divided into 3 stages. The progression of pleural fluid collection evolves from stage 1-3.

• #14 Parapneumonic Pleural Effusions and Empyema Thoracis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/298485-overview

  The evolution of a parapneumonic pleural effusion can be divided into the following three stages: Exudative, Fibrinopurulent, Organization. During the first (ie, exudative) stage, sterile pleural fluid rapidly accumulates in the pleural space. This fluid originates in the interstitial spaces of the lung and in the capillaries of the visceral pleura as a consequence of increased permeability. The pleural fluid has a low white blood cell (WBC) count and a relatively low LDH level. Its glucose and pH levels are within the reference range. These effusions resolve with antibiotic therapy, and chest tube insertion is not required. This stage takes approximately 2-5 days from the onset of pneumonia. […] In the second (ie, fibrinopurulent) stage, bacterial invasion of the pleural space occurs, with accumulation of polymorphonuclear leukocytes, bacteria, and cellular debris. A tendency toward loculation and septation exists, pleural fluid pH ( 7.20) and glucose levels are lower ( 60 mg/dL), and LDH levels increase. At this stage, bacteriologic stains or cultures of the pleural fluid can be positive for microorganisms. This stage takes approximately 5-10 days after pneumonia onset.

• #14 Parapneumonic Pleural Effusions and Empyema Thoracis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/298485-overview

  In the third (ie, organization) stage, fibroblasts grow into the exudates from both visceral and parietal pleural surfaces, producing an inelastic membrane called a pleural peel. the pleural fluid is thick. In an untreated patient, pleural fluid may drain spontaneously through the chest wall (ie, empyema necessitatis [necessitans]). Empyema thoracis may arise without an associated pneumonic process (eg, from esophageal perforation, trauma, a surgical procedure in the pleural space, or bloodstream infection [BSI]). This final stage may take 2-3 weeks to develop.

• #15 Pneumonia and empyema: causal, casual or unknown – McCauley – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4297/html

  In the early exudative stage there is a rapid outpouring of fluid and inflammatory cells into the pleural space due to increased capillary microvascular permeability. This directly results from proinflammatory cytokines, such as interleukin 8 (IL-8) and tumor necrosis factor (TNF-). […] Patients can progress to stage 2, the fibrinopurulent stage within hours if effective treatment is not provided. This next stage is characterized by deposition of fibrin clots and fibrin membranes in the pleural space, leading to loculations and isolated collections of fluid. […] If stage 2 pleural fluid is not drained in conjunction with effective antibiotic therapy, the effusion may progress to stage 3, the organizing stage. This final stage is characterized by fibroblasts that proliferate and invade the pleural fluid from both the visceral and parietal pleura, forming a thick pleural peel.

• #16 Parapneumonic Pleural Effusions and Empyema Thoracis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26643

  Pneumonia is the most frequent cause of parapneumonic effusions and empyema thoracis. Empyema may result as a complication of cardiothoracic surgery. Trauma can also lead to infection of the pleural space. The infecting organism may have spread from blood or other organs into the pleural space. […] Both viruses and bacteria can cause parapneumonic effusions, but it is the latter that is the most common cause of empyema thoracis. […] The stages of parapneumonic effusion are: Exudative stage, in which there is an accumulation of fluid in the pleural space due to increased capillary permeability that results from proinflammatory cytokines, such as interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-a). The pleural fluid in this early stage is usually clear exudative fluid with a predominance of neutrophils. Pleural fluid in this stage is simple parapneumonic effusion that usually resolves with adequate antibiotic treatment of pneumonia without the need for drainage. This stage takes approximately 2 to 5 days from the onset of pneumonia.

• #16 Parapneumonic Pleural Effusions and Empyema Thoracis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/26643

  Fibrinopurulent stage, which can develop if adequate treatment is not provided. In this stage there is a deposition of fibrin clots and fibrin membranes in the pleural cavity, leading to fluid loculations. This stage takes about 5 to 10 days after pneumonia onset. […] Organizing stage, in which fibrin membranes are transformed by fibroblast into a thick nonelastic pleural peel, resulting in the trapped lung with restrictive respiratory dysfunction. This stage may take about 2 to 3 weeks to develop. […] The clinical course varies from spontaneous healing to chronic empyema and fibro-thorax with trapped restricted lung.

• #17

  https://journals.lww.com/jmas/fulltext/2007/03040/thoracoscopic_management_of_empyema_thoracis.5.aspx

  The exudative phase is frequently adequately treated by thoracentesis or closed chest tube thoracostomy alone, with appropriate antibiotics. This phase is marked by an exudative effusion which may or may not be culture positive, is frequently not loculated but free-flowing and has a leukocytic pleocytosis with polymorphonuclear neutrophilic, eosinophilic or lymphocytic cellular infiltrate. […] The fibrinopurulent phase is marked by increasing fibrin deposition on the visceral and parietal pleura, loculation of the pleural space and a dense purulent exudate within the pleural space, which is frequently compartmentalized. The fibroblastic phase of empyema is marked by organization of fibrin into collagenous scar, with contracture of the fibrin peel on the visceral pleura resulting in entrapment of the lung at a lower FRC (functional reserve capacity) and frequently contraction of the hemithorax.

• #17

  https://journals.lww.com/jmas/fulltext/2007/03040/thoracoscopic_management_of_empyema_thoracis.5.aspx

  The cytokine response to parapneumonic empyema has been referenced by Dal Nogare et al. Infection stimulates the simultaneous expression of multiple pro-inflammatory cytokines, such as TNF- (tumor necrosis factor, alpha), interleukin IL-1, IL-2, IL-6 and TGF- (transforming growth factor beta); this last cytokine in turn stimulates over-expression of PAI-1 (plasminogen activator inhibitor, type 1) in the pleura. […] Expression of this cytokine causes inhibition of the normally ubiquitous pleural-derived tissue plasminogen activator, which leads to the inactivation of natural pleural fibrinolytic mechanisms. Ultimately, this results in fibrin deposition and accumulation, which promotes loculation of dense pleural exudate.

• #18 Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema | Scientific Reports

  https://www.nature.com/articles/s41598-021-81053-6

  Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. […] The pleural levels of four cytokines (MIF, MIP-3, IL-1, ENA-78) were highest and significantly increased in CPPE/empyema compared with those in other etiologies. […] In conclusion, our results show that elevated MIF and MIP-3 may be used as novel biomarkers for PPE diagnosis, particularly in patients with CPPE/empyema; the findings indicate that dysregulated cytokine expression may provide clues about the pathogenesis of pleural infection. […] The progression of PPEs to CPPE/empyema is associated with poor clinical outcome and increased mortality. […] In patients with parapneumonic effusion, pleural MIF may be released by macrophages, lymphocytes, and pulmonary epithelial cells in response to microbial stimuli, and MIF may contribute to the chemoattraction of neutrophils to the pleural cavity and enhance the production of other cytokines in PPE.

• #19 Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema

  https://www.mdpi.com/1999-4923/15/5/1498

  The incidence of empyema is increasing and associated with a mortality rate of 20% in patients older than 65 years. […] A Streptococcus pneumoniae-induced rabbit model of chronic empyema recapitulates the progression, loculation, fibrotic repair, and pleural thickening of human disease. […] Plasminogen activator inhibitor 1 (PAI-1) is overexpressed in pleural fluids in empyema by up to three orders of magnitude, and is the most effective mechanism-based inhibitor (serpin) of tissue (tPA) and urokinase (uPA) plasminogen activators. […] We hypothesized that neutralizing intrapleural PAI-1 pharmacologically would increase the efficacy of fibrinolytic therapy, and, thus, in a significant decrease in the dose of plasminogen activators needed for successful treatment. […] Our results demonstrate that targeting the PAI-1 mechanism increases the efficacy of single chain (sc) tPA (Alteplase) and scuPA in rabbit models of chemically induced pleural injury and acute, early-stage empyema to 8-fold.

• #19 Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema

  https://www.mdpi.com/1999-4923/15/5/1498

  In humans, delaying treatment leads to a late-stage, chronic empyema more resistant to IPFT, with increasing time to treatment correlating with increased failure of fibrinolytic therapy. […] Thus, the chronic empyema model recapitulates increased resistance of advanced human empyema to fibrinolytic therapy, thus allowing for studies of multi-injection treatments. […] The results of IPFT with single bolus injection of sctPA or scuPA support the clinical notion that IPFT treatments for acute and advanced-stage empyema likely differ, with the latter having a higher chance of failure. […] Fibrin structure maturation and an increase in intrapleural scarring (substitution of fibrin with collagen) could adversely affect the rate of fibrinolysis and contribute to failure of IPFT. […] Thus, PAI-1-TFT affects the PAI-1 mechanism, protecting fibrinolysin from inhibition by any form of active PAI-1, increasing intrapleural half-life of the fibrinolysin, and supporting slow fibrinolysis. […] The validity of our model is supported by its similarity to clinical presentation of advanced-stage empyema and responses to fibrinolytic therapy with human-tailored drugs, recapitulating findings observed in a clinical setting.

• #20 Pleural empyema | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/pleural-empyema-1?lang=us

  Pleural empyema refers to a collection of pus in the pleural cavity which may contain gas locules. Empyema is usually unilateral and most often occurs as a complication of pneumonia or perforated esophagus. The thickened pleura demonstrates contrast enhancement and the visceral and parietal components separate around the collection causing the split pleura sign. […] Offending organisms vary somewhat according to the age at which the empyema develops and the underlying cause. For parapneumonic empyemas the most frequent organisms are: childhood – Pneumococcus; adults – penicillin-resistant Staphylococcus aureus, gram-negative bacteria, anaerobic bacteria: usually polymicrobial. In the setting of trauma or thoracic surgery, Staphylococcus aureus is usually involved. Other uncommon causes include mycobacterial infection, resulting in tuberculous empyema.

• #21 Pleural empyema

  https://pch.health.wa.gov.au/For-health-professionals/Clinical-Practice-Guidelines/Pleural-empyema

  Pleural empyema develops most commonly secondary to bacterial pneumonia. […] The most common pathogens in Australia are Streptococcus pneumoniae and Staphylococcus aureus (both methicillin susceptible S.aureus – MSSA and methicillin resistant S.aureus – MRSA). […] Intrapleural Alteplase (tissue type plasminogen activator, tPA) should be instilled from the outset if the pleural fluid obtained is turbid or if there is evidence of loculations on ultrasound. […] Intrapleural interventions have been associated with significantly shorter hospital stays compared with intravenous antibiotics alone, while instillation of intrapleural fibrinolytics offers benefit beyond simple chest tube drainage in shortening length of hospital stay.

• #22 The Clinical Features and Management of Empyema Caused by Streptococcu | IDR

  https://www.dovepress.com/the-clinical-features-and-management-of-empyema-caused-by-streptococcu-peer-reviewed-fulltext-article-IDR

  Streptococcus constellatus, a commensal, plays an important role in purulent infections. It has been reported as aggressive pathogen causing pleural empyema. But the role of S. constellatus in empyema has not been taken seriously. […] S. constellatus may cause pneumonia and lung abscess first and then spread to cause empyema mainly in old males with comorbid diseases. S. constellatus often co-isolated with anaerobes in empyema. Antibiotics should cover simultaneously both S. constellatus and anaerobes. […] The high-risk factors for S. constellatus empyema include diabetes mellitus, oral infection, and oral surgery. […] SMG was considered causing thoracic infections via some pathways, including aspiration of oral secretions, direct implantation by trauma or surgery, extension by contiguity, and hematogenous dissemination.

• #22 The Clinical Features and Management of Empyema Caused by Streptococcu | IDR

  https://www.dovepress.com/the-clinical-features-and-management-of-empyema-caused-by-streptococcu-peer-reviewed-fulltext-article-IDR

  We speculated that S. constellatus mainly caused pneumonia and lung abscess first and then spread to cause empyema. […] S. constellatus were reported more likely to be polymicrobial in suppurative infections. […] Although low mortality (11.1%) was showed in patients with S. constellatus empyema, more than half developed respiratory failure and 33.3% develop severe pneumonia, even ARDS and septic shock. […] In addition to antibiotics and drainage, two patients in our study and six patients with S. constellatus empyema in the literature were cured by surgical treatment, including decortication and excision of the lung lobe with lung abscess. […] We explored the cause of the patients death and concluded that empyema caused by S. constellatus and anaerobes and subsequently severe pneumonia caused by DTR P. aeruginosa contributed to the patients death.

• #23 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Empyema.aspx

  The fluid in an empyema is filled with an infectious agent, such as tuberculosis (TB) or Staphylococcus, although many others have been identified. Most empyemas result from acute bacterial cases of pneumonia or abscesses. […] Some empyemas are culture-negative and are sterile pleural collections that include augmented levels of inflammatory mediators, which result in systemic effects which are clinically indistinguishable from true empyema collections. This may occur because of thoracic surgery combat trauma or occasionally, from the dissemination of extrapulmonary sites or direct spread through the diaphragm for my subphrenic abscess. If empyemas drain into the chest wall or beyond, into soft tissue, a form of empyema called empyema necessitans, results. […] Empyemas developed in three stages. The first is referred to as the exudative stage in which a low viscosity fluid forms. Following this, the fibrinopurulent stage, which is a transitional phase with heavy fibrinous deposits and turbid fluid occurs. Finally, in the organizing stage, capillary growth is seen with the lung trapping by collagen. This process typically occurs over six weeks.

• #24 Salmonella empyema: a case report | Pneumonia | Full Text

  https://pneumonia.biomedcentral.com/articles/10.1007/BF03371465

  Non-typhi Salmonella enterica infection rarely presents as a pleural empyema, with only 31 cases published in the literature over the last century. […] Non-typhi S. enterica serovars rarely cause pleuropulmonary disease, in particular pleural empyema. […] The hypothesised pathogenesis of focal infections such as empyema includes bacteraemia with subsequent seeding in patients presenting with positive blood cultures for S. enterica. […] Other causes include seeding from nearby infection such as the spleen and pancreas, with subsequent transdiaphragmatic tracking. […] Therefore, isolation of an enteric organism, such as Salmonella, from a pleural effusion should prompt clinicians to exclude an intra-abdominal source of infection. […] It is suspected that non-typhi Salmonella may be dormant in the reticulo-endothelial system, with subsequent re-activation and haematogenous spread. […] The sensitivity of detection by blood culture also declines with longer duration of the illness.

• #25 Empyema: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000123.htm

  Empyema is usually caused by an infection that spreads directly from the lung. It leads to a buildup of pus in the pleural space. […] In rare cases, empyema can occur after thoracentesis. This is a procedure in which a needle is inserted through the chest wall to remove fluid in the pleural space for medical diagnosis or treatment. […] The goal of treatment is to cure the infection. This involves the following: Placing a tube in your chest to drain the pus. Giving you antibiotics to control the infection. […] When empyema complicates pneumonia, the risk for permanent lung damage and death goes up. Long-term treatment with antibiotics and drainage are needed.

• #26 Empyema – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1008

  Empyema is defined as the presence of pus in the pleural space. […] A simple parapneumonic effusion is not infected, whereas a complicated parapneumonic effusion develops once infection has spread to the pleural space. These three conditions represent a spectrum of pleural inflammation in response to infection, ranging from a simple parapneumonic effusion to empyema. […] Risk factors include pneumonia, iatrogenic intervention in the pleural space, diabetes, and alcohol abuse.

• #27 Empyema: Causes, Types, and Symptoms

  https://www.healthline.com/health/empyema

  If the infection continues to get worse, it can lead to the formation of a thick peel over the pleura, called a pleural peel. This peel prevents the lung from expanding. Surgery is required to fix it. […] Treatment is aimed at removing the pus and fluid from the pleura and treating the infection. Antibiotics are used to treat the underlying infection. The specific type of antibiotic depends on what type of bacteria is causing the infection. […] The method used to drain the pus depends on the stage of the empyema. […] In the later stages, or complex empyema, a drainage tube must be used to drain the pus. This procedure is usually performed under anesthesia in an operating room. […] In this surgery, your surgeon will peel away the pleural peel. […] However, in people with other conditions that compromise the immune system, empyema can have a mortality rate as high as 40 percent. […] If its not treated, empyema can lead to potentially life-threatening complications such as sepsis.

• #28 Predictors and Clinical Outcomes in Empyema Thoracis Patients Presenting to the Emergency Department Undergoing Video-Assisted Thoracoscopic Surgery

  https://www.mdpi.com/2077-0383/8/10/1612

  Empyema thoracis is a collection of purulent fluid in the pleural space that mainly occurs with pneumonia or secondary to chest trauma/surgery. Approximately half of the patients with pneumonia develop pleural effusion, and 5–10% of patients may develop empyema thoracis after antibiotic treatment. It evolves from stage I (exudative), through stage II (fibrinopurulent), to stage III (organized) for 3 to 6 weeks. Patients may have a fever, chest pain, and cough in the early stage, whereas dyspnea may occur in the late stage. Treatment includes antibiotics, chest tube drainage, surgical intervention with video-assisted thoracoscopic surgery (VATS), or open thoracotomy. However, empyema thoracis is still a common problem, with high morbidity and mortality rates as a result of suboptimal management. Despite the use of antibiotics and different pneumococcal vaccines in clinical care, and improvement of the minimally invasive surgical techniques, empyema remains the most common complication of pneumonia with a reported mortality rate between 10% and 20%. Recent consensus guidelines show that the use of a chest tube as the first-line treatment still needs further examination. A cohort study in 2018 characterized the higher readmission and reintervention rates in patients with thoracic empyema treated with chest tubes, and suggested earlier surgical intervention. Adequate treatment of thoracic empyema is stage-dependent, and surgical intervention will be considered when antibiotic therapy and fluid drainage do not achieve infection control successfully, along with good re-expansion of the lung. Since the progression of thoracic empyema is fluent, stratification by stage and treatment depend on the surgeon’s experience and judgment. Although a systematic review demonstrated that treatment with VATS had superior outcomes for pleural empyema, even as the first-line management, no consensus currently exists about the timing for choosing VATS for the initial treatment. This study focused on patients presenting to the emergency department (ED) with suspected empyema thoracis. Knowing the risks for death related to treatment with VATS may enable surgeons to optimize therapeutic strategies for definitive surgical management to avoid postoperative complications, and even to reduce mortality.

• #28 Predictors and Clinical Outcomes in Empyema Thoracis Patients Presenting to the Emergency Department Undergoing Video-Assisted Thoracoscopic Surgery

  https://www.mdpi.com/2077-0383/8/10/1612

  Evaluating and diagnosing through early identification of the microbial etiologies would guide early targeted antimicrobial therapy and improve clinical outcomes. Our data showed the S. aureus and methicillin-resistant S. aureus were the most frequently identified pathogen in the non-survivor group, which is in agreement with published data on the etiology of pleural empyema undergoing surgical treatment. It is important to note that Viridans streptococci and Mycobacteria tuberculosis are the most common cause of empyema in the survivor group, which may be easily overlooked. […] The indication for and timing of surgical intervention in the management of empyema remains controversial, especially in children. An important consideration to perform any surgical procedure is to weigh the benefits against the risks in the appropriate patients, to improve overall outcomes. In this study, we evaluated the possible risk factors of empyema thoracis treatment by VATS from the ED patients’ records. Early surgical intervention and multidisciplinary care can decrease the mortality rate, especially for those who present to ED with the symptom of chest pain.

• #29

  https://journals.lww.com/lungindia/fulltext/2006/23030/decortication_in_chronic_pleural_empyema.2.aspx

  Empyema thoracis remains a common thoracic problem with challenging management strategies. […] The variable success rates and management strategies depend in part on stage of the empyema at presentation. Empyema thoracis has many causes but the most common cause is pulmonary infection. […] If empyema is not managed properly it progresses through exudative phase and firbrinopurulent phase to organizing chronic phase. An empyema cavity is formed and visceral pleural fibrosis limits re-expansion of the lung. […] Because many of the infections that cause empyema are indolent, a physician often sees patient after it has reached the firbrino-purulent or organized stage. […] Decortication is the safe and effective treatment in the organized empyema, enabling complete expansion of lung34. […] The therapy of empyema thoracis requires appropriate antibiotics, prompt drainage and lung re-expansion.

• #29

  https://journals.lww.com/lungindia/fulltext/2006/23030/decortication_in_chronic_pleural_empyema.2.aspx

  Success rate of various therapeutic procedures in management of empyema depends at least partly on the stage of empyema at presentation5. […] But if empyema is not managed properly in early stage, it will progress to fibrino-purulent and organized chronic stage. […] Late empyema, which have reached the organized phase are characterized by the presence of thick pleural peel causing varying degree of pulmonary parenchyma entrapment. […] There are many surgical studies that show decortications to be safe and effective for treating empyema1011121314. […] In general, both VATS and open decortications have been shown to be safe and effective in the organized empyema enabling complete lung expansion1011121314. […] This study emphasizes that decortication should be considered early in a patient of chronic organized empyema, enabling complete expansion of the lung and preventing morbidity.

• #30 Empyema and Parapneumonic Effusions: General Considerations | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/empyema-and-parapneumonic-effusions-general-considerations

  The fibrous phase (Stage III) is best avoided by NOT DELAYING drainage during the earlier stages. This phase starts in 4-6 weeks and is characterized by the formation of a thick, fibrous rind (peel or cortex) on the visceral pleural surface of the lung. […] Development of this fibrotic process in the chest is called fibrothorax. Even after drainage of the effusion the lung cannot appropriately expand (trapped lung). […] The persistence of loculated effusions may depend on their etiology (which bacterial pathogen), appropriateness of antibacterial treatment, and an individual patient’s physiologic and anatomic characteristics. Failure to drain the effusion results in progression of the inflammatory process, entrapped lung, and long-term decreased respiratory capacity.

• #31 Risk factors for tuberculous empyema in pleural tuberculosis patients | Scientific Reports

  https://www.nature.com/articles/s41598-019-56140-4

  Currently, the pathogenesis of empyema is not well understood. TE, is less common and represents an infection of the pleural space by M.TB that provokes the accumulation of purulent pleural fluid. TE usually develops due to chronic pulmonary TB, and rarely as a result of untreated tuberculous pleural effusion (TPE). Prior to the diagnosis of TE, patients often have suffered from chronic pulmonary TB for more than 10 years. This is due to the fact that most of TE patients are asymptomatic. Nevertheless, sputum culture positive for M.TB is also considered as a gold standard criteria for TPE diagnosis. Therefore, the TE secondary to pulmonary TB would be more easily detected, because of the additional specimen (sputum) examined. Then, anti-TB drugs would be given timely, in other words, this may have a positive effect on the prognosis of TE patients. In addition, Ornstein GG et al. suggested that, when the underlying pulmonary TB is under control, the prognosis of TE is good; nevertheless, when the associated pulmonary TB not under control, the prognosis is not good. This also indicates that an increased association between pulmonary TB and TE outcomes is plausible. High levels of pleural ADA and peripheral WBC count predict increased TE risk. The findings suggest that the two biomarkers may reveal the progression of TE. Several reports have discovered the diagnostic role of the two in patients with empyema. For the treatment of empyema, the stage of its development is the main parameter to be considered. However, currently there is no biomarker available that would help to choose appropriate interventions.

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