Empyema and Abscess Pneumonia

A lung abscess is a subacute infection in which an area of necrosis forms in the lung parenchyma. It usually is in a dependent section of the lung, more often involves the right lung than the left, and is most commonly seen after aspiration of oropharyngeal secretions. Lung abscesses have a slow, insidious presentation and usually develop 1-2 weeks after the initial aspiration event. A lung abscess is shown in the image below.

Empyema is defined as pus in the pleural space. It typically is a complication of pneumonia. However, it can also arise from penetrating chest trauma, esophageal rupture, complication from lung surgery, or inoculation of the pleural cavity after thoracentesis or chest tube placement. An empyema can also occur from extension of a subdiaphragmatic or paravertebral abscess.

A lung abscess involves the lung parenchyma, whereas an empyema involves the pleural space.[1] In many patients with pneumonia, a sterile simple parapneumonic effusion develops in the pleural space. If this pleural effusion becomes infected, it is labeled a complicated parapneumonic effusion, whereas the presence of frank pus in the pleural space defines an empyema.

The development stages of an effusion can be divided into three phases: exudative, fibropurulent, and organizational. The initial effusion develops from increased pulmonary interstitial fluid along with progressive capillary vascular permeability. A simple effusion is frequently sterile and resolves with antibiotic treatment of the underlying pulmonary infection.

In 5-10% of the patients with a pleural effusion, the effusion becomes infected and neutrophils buildup. This inflammatory response, shown in the images below, also causes the production of chemokines, cytokines, oxidants, and protease mediators.

This more complicated parapneumonic effusion requires both antibiotics and some form of surgical drainage or alternative treatment modality to remove the purulent effusion. In these more complicated effusions, decreased fibrinolysis and activation of the coagulation cascade leads to the production of fibrin with subsequent adhesions and loculated fluid collections. This process ultimately can cause pleural fibrosis and impairment of lung expansion.

The most common cause of lung abscess is aspiration. Risk factors include the following:

• Poor dentition, periodontal infection[2]

• Seizure disorder

• Alcohol and drug abuse

• Electronic cigarette use[3]

• Diabetes mellitus

• COVID-19[4]

• Gastroesophageal reflux disease

• Inability to protect the airway because of an absent gag reflex (eg, patients who are comatose, have a change in mentation or bulbar dysfunction,[5] or who might be undergoing general anesthesia)

• Primary lung disorders, such as septic emboli, pulmonary vasculitis, cavitating lung malignancy, or pulmonary cystic disease

• Penetrating chest trauma

• Immunosuppression

• Conditions associated with septic emboli, including intravenous drug use, soft tissue infections, valvular heart disease, and individuals with intravascular prosthetic material

Polymicrobial bacteria can be found in over 90% cases of lung abscess.[6] The microbiologic organisms are typically oral flora, including Bacteroides, Fusobacterium, and Peptostreptococcus species. Other organisms include Pseudomonas species, Klebsiella species, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus milleri, Nocardia species, and less commonly fungi and parasites. Immunosuppressed individuals are at increased risk for more opportunistic pathogens associated with lung abscess, including Mycobacterium tuberculosis (especially in cases of immigration from Africa or Asia), Pseudomonas, Klebsiella, Nocardia, and fungi.[7]

Klebsiella pneumoniae has been shown to have a significant preponderance for severe, necrotizing pneumonia and subsequent development for cavitary lesions and lung abscesses.[7] A Taiwanese study found an increasing incidence of K pneumoniae in community-acquired lung abscesses.[8] However, there is a higher incidence of K pneumoniae related infection found in Taiwan, and this trend may not translate to the US and other parts of the world.[9] Staphylococcus aureus is the most common isolated pathogen of lung abscess in children.[6]

The most common cause of an empyema is from a parapneumonic effusion that becomes infected; these account for about half of all empyemas. Other causes of an empyema include the following:

• Penetrating chest trauma

• Undrained hemothoraces, including those secondary to blunt chest trauma

• Contamination of a wound during procedures such as needle decompression, chest tube placement, thoracentesis, or thoracic surgery

Microbiologic organisms that can cause an empyema include Streptococcus species such as Streptococcus milleri (Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus), S pneumoniae, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), and a variety of gram-negative organisms and anaerobes.[10, 11] Anaerobic involvement, either as sole organism or part of a polymicrobial infection, is common in empyemas but may be difficult to detect on cultures.[11] One should always consider enterobacteria, enterococci, and Mycobacterium tuberculosis as potential pathogens.

Bacteria from the Streptococcus milleri group have become the predominant organism cultured from adults with empyemas, especially in patients with underlying malignancy or diabetes mellitus. Recently, the incidence of staphylococcal-related empyema has increased.

In the pediatric population, S pneumoniae remains the predominant organism associated with empyemas. S aureus and Pneumococcal serotypes 1, 3, and 19A, possibly secondary to the widespread use of the pneumococcal conjugate vaccine, have seen dramatic increases more recently.[12]

United States data

The rates of lung abscess have dropped significantly since the development of antibiotics. The frequency of lung abscess varies depending on underlying comorbidities and occurs most frequently in individuals with risk factors for aspiration (stroke, dementia, alcoholism, gastric reflux, and poorly controlled epilepsy), immunocompromise, malignancy, intravenous drug use, poor dental hygiene, and diabetes mellitus.[1]

In the 1940s, the rates of empyema had dropped precipitously with the advent of antibiotics, but, from 1996 to 2008, the rate of empyema nearly doubled across all age groups. This increase is partly explained by the rapid increase of antibiotic resistance but, interestingly, is theorized to have occurred secondary to a replacement phenomenon. The heptavalent pneumococcal vaccine had dramatically decreased the overall incidence of pneumococcal infections but had increased the incidence of nonvaccine pneumococcal serotypes 1, 3, and 19A and nonpneumococcal infections, especially Staphylococcus aureus, that are thought to confer a higher conversion from pneumonia to complicated pneumonia and empyema. Since 2010, a 13-valent pneumococcal conjugate vaccine has been available, which includes the 1, 3, and 19A serotypes.[12, 13]

Most empyemas are complications of pneumonia, but up to 20% are secondary to iatrogenic causes, including but not limited to, thoracic surgeries, chest tube insertion, or thoracentesis. Three percent of empyemas are estimated to occur as complications of chest trauma.[14]

Sex- and age-related statistics

A population study revealed that nearly 65% of individuals with parapneumonic empyema are male.[10] No studies have revealed male gender as an independent risk factor for empyema.[15, 16] This disparity may be attributed to gender-related risk factors, including alcohol abuse, drug use, and delay to treatment.

Lung abscesses are more common in individuals with comorbid conditions often found with increasing age, including dementia and malignancy.

There is an increased risk of parapneumonic empyema with extremes of age with rates of 7.6 and 9.9 cases per 100,000 for ages younger than 5 years and older than 64 years, respectively. Rates for empyema between ages of 5 and 64 years range from 1.9-5.4 cases per 100,000.[10, 13]

The prognosis for both lung abscess and empyema generally is good. Ninety percent of lung abscesses are cured with medical management alone.

Morbidity/mortality

The mortality rate for lung abscesses in adults can reach as high as 15-20%,[17] whereas children have mortality rates typically below 5%. Mortality is largely dependent on comorbid conditions. Healthy individuals generally have a very good prognosis while immunosuppression, malignancy, nosocomial infections, reduced level of consciousness, anemia, and low albumin portend a poorer prognosis. Lung abscesses secondary to Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae infections have high mortality rates.[17]

The case fatality rate in the United States for parapneumonic empyema is 7.2%, with rates increasing with age. The fatality rate in children is 0.4%, and is 16.1% in adults older than 64 years.[10] Mortality is increased for hospital acquired, S aureus, gram-negative, and mixed aerobic infections.

Complications

Complications of pulmonary abscess include pleural fibrosis, trapped lung, restrictive ventilatory defect, bronchopleural fistula, and pleurocutaneous fistula.

The patient's history may reveal the following findings:

• Recent diagnosis and treatment of pneumonia

• Recent history of penetrating chest trauma or diaphragmatic injury (should raise clinical suspicion for empyema)[18]

• Cough productive of bloody sputum that frequently has a fetid odor or offensive appearance

• Fever

• Shortness of breath

• Anorexia, weight loss

• Night sweats

• Pleuritic chest pain

At the onset, the cough is non-productive, but a productive cough is the typical sign, sometimes followed by hemoptysis. Clubbing fingers may be present in patients with chronic abscess.[6]

Chalmers et al in a prospective observational study identified six risk factors that were associated with patients admitted with community-acquired pneumonia who subsequently developed a complicated parapneumonic effusion or empyema. These factors include albumin < 30 g/L, sodium < 130 mmol/L, platelet count >400 X 109, C-reactive protein >100 mg/L, and a history of alcohol abuse or intravenous drug use.[15] Other predispositions to development of a parapneumonic effusion and empyema include immunosuppression (eg, HIV, diabetes mellitus, malnutrition), gastrointestinal reflux, poor dental hygiene, bronchial aspiration, and chronic lung disease.

The physical examination may reveal the following findings:

• Temperature frequently elevated but usually not greater than 102°F

• Tachypnea

• Rales

• Rhonchi

• Egophony

• Tubular breath sounds

• Decreased breath sounds

• Dullness to percussion

Relevant laboratory studies include the following:

• A CBC with differential may reveal a leukocytosis and a left shift.

• Collect sputum for Gram staining, culturing, and sensitivity testing.

• If tuberculosis is suspected, acid-fast bacilli testing should be obtained.

• In the presence of fever, obtaining a blood culture may be appropriate.

Additional potentially useful tests include the following:

• Pulse oximetry to assess oxygenation

• ABG or VBG analysis to assess respiratory adequacy

• Transtracheal aspiration for culturing (if sputum findings are nondiagnostic)

Perform chest radiography to diagnose and differentiate pneumonia, pulmonary abscess, and empyema. Distinction of these conditions is important because lung abscesses and pneumonia require medical treatment, while empyema frequently requires definitive surgical intervention. Several radiographs are shown below.

On the chest radiograph, a lung abscess appears as a solitary cavitary area with an air-fluid level, which typically is present in a dependent portion of the lung. A surrounding patchy area of infiltrate aids in differentiating a pulmonary abscess from a cavitary lung cancer.

On the chest radiograph, findings that suggest empyema, as opposed to lung abscess, include extension of the air-fluid level to the chest wall, extension of the air-fluid level across fissure lines, and a tapering border of the air-fluid collection.

The costophrenic angle should be closely inspected on the chest radiograph to assess the presence of fluid that suggests effusion or empyema.

On the chest radiograph obtained of the patient in an upright position, blunting of the costophrenic angle occurs when approximately 200 mL of fluid accumulates.

A lateral chest decubitus radiograph, obtained with the patient on his or her side, reveals whether the pleural fluid is mobile and forms layers or whether it is loculated.

To better assess any abnormal lung findings found on a chest radiograph, CT of the chest or ultrasonography is usually necessary. Ultrasonography is useful for needle-guided aspiration and drainage of a potential pleural effusion or empyema. When ultrasonography is not used to guide needle aspiration, the failure rate is 12-15%. Color Doppler ultrasonography can also assist in differentiating empyema from peripheral air-fluid pulmonary abscess. Chen et al reported in a retrospective study that identification of color Doppler ultrasonography vessel signals in pericavitary consolidation was useful and specific for identifying lung abscesses, with sensitivity of 94% and specificity of 100%.[19]

CT of the chest can assess for pneumonia, lung abscess, tumor, pleural effusions and septations, other pleural diseases, or pleural thickening. CT of the chest has shown increased sensitivity for detection of pulmonary infections compared to chest radiograph, especially for immunocompromised individuals. Chest CT may be considered when the index of suspicion for significant pulmonary infection is high despite a negative radiograph findings.[7]

Many clinicians recommend limiting the use of CT in children to reduce radiation exposure. Jaffe et al studied the utility of routine CT scanning in children and concluded that, while CTs detected more parenchymal abnormalities, the additional information did not alter management and it did not predict clinical outcome in patients who were being treated with chest tube drainage and fibrinolytics.[20] The British Thoracic Society guidelines conclude that chest CT has no role in the routine identification of pleural collections in children.[21]

A lung abscess in an adult is shown in the image below.

If a pleural effusion is present, a diagnostic thoracentesis may be performed and analyzed for pH, lactate dehydrogenase, glucose levels, specific gravity, and cell count with differential. Pleural fluid may also be sent for Gram stain, culture, and sensitivity. Acid-fast bacillus testing may also be considered.

The fluid may be sent for cytology if cancer is suspected.

The following findings are suggestive of an empyema or parapneumonic effusion that will likely need a chest tube or pigtail catheter for complete resolution:

• Grossly purulent pleural fluid

• pH level less than 7.2

• WBC count greater than 50,000 cells/µL (or polymorphonuclear leukocyte count of 1,000 IU/dL)

• Glucose level less than 60 mg/dL

• Lactate dehydrogenase level greater than 1,000 IU/mL

• Positive pleural fluid culture

There is increasing evidence that tumor necrosis factor (TNF)–alpha may be used to help determine whether a pleural effusion is a complicated parapneumonic effusion or an empyema.[22, 23, 24]

In acute lung abscess, there are necrotic tissue mixed with necrotic granulocytes and bacteria in the central parts. Around this area there are preserved neutrophilic granulocytes with dilated blood vessels and inflammatory edema. In chronic lung abscess, puss is present with or without bacteria. Around the abscess is a pyogenic membrane and around the pyogenic membrane are lymphocytes, plasma cells, and histiocytes in connective tissue.[6]

Treatment of lung abscesses or empyema is performed in-hospital, with consultations involving internists, pulmonologists, thoracic surgeons, and/or interventional radiologists.

All patients should undergo pulse oximetry and evaluation of their respiratory status. If respiratory failure is found or likely to occur, intubation and mechanical ventilation is necessary. Supplemental oxygen should be started for any patient who is acutely short of breath or who is hypoxic based on pulse oximetric findings.

Once the diagnosis of a lung abscess is made, parenteral antibiotics should be started. Ideally, sputum and blood culture findings should be obtained prior to the initiation of antibiotics.

After the diagnosis of empyema is made, prompt drainage by means of tube thoracostomy with use of parenteral antibiotics should be initiated.

Inpatient care is mandatory for the management and assistance of the patient's respiratory status, continuation of intravenous antibiotics, and drainage of the lung abscess or empyema as needed. Antimicrobial therapy should be continued empirically until therapy can be guided with culture results.

Transfer is usually not indicated unless advanced respiratory management or surgical drainage is not available without transfer. Patients should be transferred only after stabilization of their respiratory status and administration of intravenous antibiotics.

Lung abscesses are treated with a prolonged course of parenteral antibiotics that target organisms found in aspiration pneumonia.[5] The initial choice of antibiotics frequently is empiric, beginning with clindamycin, cefoxitin, ticarcillin, or piperacillin/tazobactam, although penicillin has been very effective when the organism is sensitive. Some authors advocate adding coverage for Klebsiella as well. Subsequent therapy should be based on sputum or blood culture results.

An empyema is treated with parenteral antibiotics and prompt surgical drainage. Empiric therapy, including anaerobic coverage, for an empyema frequently includes clindamycin, carbapenems, or beta-lactam plus beta-lactamase inhibitors like piperacillin/tazobactam until a definitive organism is identified on pleural fluid cultures and sensitivities are obtained. For an empyema secondary to aspiration pneumonia or a parapneumonic process, choose antibiotics that are active against mouth flora, S aureus, and Streptococcus species. For an empyema secondary to penetrating chest trauma, administer antibiotics that have coverage for skin flora. There should be a strong consideration to cover with vancomycin given the increasing incidence of empyema caused by MRSA. Pleural fluids or sputum specimens that are obtained should be cultured for M tuberculosis as well.

Many clinicians advocate the administration of intrapleural fibrinolytics in patients with empyemas. Intrapleural fibrinolytics assist in the breakdown of fibrin bands that can cause loculation of the empyema and allow for better chest tube drainage of the infected material. A meta-analysis that included 761 patients showed that intrapleural fibrinolytic therapy confers significant benefit in reducing the requirement for surgical intervention for patients.[25] However, some randomized clinical trials have reported opposite results, with these studies suggesting no benefit in outcomes with fibrinolytic therapy.[26]

Lung abscesses typically respond well to antibiotic therapy, but when that therapy is unsuccessful, the consulting clinician might consider percutaneous catheter drainage or endoscopic surgical resection of the involved area of the lung (see Lung Abscess Surgery). Surgery is required in 11-21% of cases[27] and is often indicated for complications, including severe hemoptysis or development of bronchopleural fistula[28] or empyema, and abscesses larger than 6 cm, associated with obstructing neoplasms, or secondary to Pseudomonal infections.[29]

Interventional radiographic management has become a well-established treatment and is becoming an increasingly safe and effective means of treating lung abscesses. The success rate of CT-guided drainage of a lung abscess is up to 90% and is associated with fewer complications, less pain, and shorter hospital stays.[30]

The overall success rate of percutaneous tube drainage (PTD) has been reported in one study as 84% with a complication rate of 16%. PTD is associated with less morbidity and mortality than surgical resection.[31]

Complicated parapneumonic effusions or empyemas require drainage in addition to medical therapy to ensure a good prognosis. Traditionally, a large caliber, chest thoracostomy tube has been placed to drain the fluid in an effort to avoid further surgical intervention. More recently, CT- or US-guided pigtail drainage catheters, smaller than 14F, have been used with comparable results but with much less pain.[30]

If chest tube or pigtail catheter drainage and fibrinolytic treatment are unsuccessful, many authors recommend video-assisted thoracic surgery (VATS) next rather than the more traditional open thoracotomy. VATS is less invasive and well tolerated, with outcomes that compare favorably with open thoracotomy.[32]

Prevention of aspiration is important to minimize the subsequent risk of lung abscess. The risk of aspiration can be reduced by cessation of alcohol and drug abuse, good dental hygiene, good nutrition, and management of gastroesophageal reflux disease. Early intubation should be performed in patients who do not have a gag reflex or are in the process of respiratory failure.

The 13-valent pneumococcal conjugate vaccine (PCV13) has been found to reduced parapneumonic empyema among US children under the age of 18 years.[33] In addition, the hospitalization rate for all types of empyema reached a historic low among children younger than 2 years in the two year period following the introduction of PCV13 in both the US and the UK.[33, 34]

The American Association of Thoracic Surgery (AATS) has released consensus guidelines for the management of empyema. The guidelines were developed by a multidisciplinary group of experts and were based on a comprehensive review of the literature, as well as on expert opinion when high-quality evidence was not available. Key recommendations include the following[35] :

• Patients with pneumonia that fail to respond to established antibiotic therapy or unexplained sepsis should always be evaluated for a possible pleural effusion. If either a parapneumonic effusion or empyema is found, patients should undergo immediate treatment.

• Pleural ultrasound should be done routinely in addition to conventional chest X-ray to evaluate pleural space infection, both for diagnostic purposes and image guidance for pleural interventions.

• To establish a diagnosis of empyema, clinicians should consider the presence of pus, positive Gram's stain, or culture.

• A pleural pH below 7.2 in a patient with suspected pleural space infection predicts a complicated clinical course, and tube thoracostomy should be done followed by surgical intervention when appropriate.

• In patients with community-acquired empyema, a parenteral second- or third-generation cephalosporin plus metronidazole or parenteral aminopenicillin with beta-lactamase inhibitor.

• For those with hospital-acquired or postprocedural empyema, antibiotics should include those active against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

• Aminoglycosides should be avoided, and antibiotic therapy should be chosen based on culture results when possible

• In stage II acute empyema, video assisted thoracoscopic surgery (VATS) should be the first-line treatment.

The American Pediatric Surgical Association Outcomes and Clinical Trials Committee published guidelines for the diagnosis and management of empyema in children. Recommendations include the following[36] :

• Once an effusion is diagnosed as empyema, definitive management should be initiated with mechanical (VATS) or chemical debridement (fibrinolysis)

• Operative management should be reserved for patients who fail to respond to chemical debridement if healthcare resources allow for such management.

• Consideration for VATS after chemical debridement should occur when the patient is persistently ill after the chest tube drainage is diminished and imaging proves substantial pleural space disease.

The AATS guidelines noted that there is disagreement about the best treatment protocols for children with empyema. After a comprehensive analysis of current literature, the guidelines recommendation was that pediatric patients should initially be treated with a tube thoracostomy with or without the subsequent instillation of fibrinolytic agents.[35]

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Clindamycin (Cleocin)

Lincosamide for the treatment of serious skin and soft-tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Cefoxitin (Mefoxin)

Second-generation cephalosporin indicated for infections with gram-positive cocci and gram-negative rod. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms; traditional drug for the treatment of lung abscess, but its spectrum of activity is narrow.

Ticarcillin/clavulanate (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during active growth stage. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive bacteria, most gram-negative bacteria, and most anaerobes.

Piperacillin/tazobactam (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.

Imipenem and cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity.

Vancomycin (Vancoled, Vancocin, Lyphocin)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or whose conditions are unresponsive to penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal-penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients with renal impairment.