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forms in the pleural space adjacent to a pneumonia. When microorganisms infect the
pleural space, a complicated parapneumonic effusion or empyema may result. An
empyema can also develop in the absence of an adjacent pneumonia.
EPIDEMIOLOGY
Rates are highest in hospitalized patients with one report suggesting that 20 to 40
percent of patients hospitalized with pneumonia have a parapneumonic effusion and
5 to 10 percent of those progress to empyema (ie, about 32,000 patients per year)
[3].
Differences in reporting rates between studies may reflect differences in how studies
define parapneumonic effusion; studies evaluating the incidence of computed
tomography (CT)-defined fluid in pneumonia report higher rates than those that are
defined by fluid chemistry and culture.
Empyema may be more common in men than women, although the reasons for this
are unknown [7-9].
to underlying pneumonia, and are believed to develop in three stages (figure 1).
Patients can present at any stage of development (table 2).
It is prudent that the clinician be aware of their local microbiology and antibiotic
resistance patterns and be cognizant of the likelihood of infections that are
polymicrobial (eg, coexisting anaerobes).
Selected patients may also have increased risk of specific organisms. Patients with
diabetes mellitus are at increased risk of empyema secondary to Klebsiella
pneumoniae [28]. In patients with influenza, the major causes of bacterial
superinfection and empyema have been Staphylococcus aureus, Streptococcus
pneumoniae, and Streptococcus pyogenes [29]. Anaerobic empyema with aspiration
pneumonia often is seen in the aspiration-prone patient who presents relatively late
in the infection with pneumonitis involving the superior segment of a lower lobe or
posterior segment or an upper lobe.
and empyema are nonspecific and, with the exception of decreased fremitus, overlap
with those of pneumonia. Among those with pneumonia, risk factors for empyema
(eg, aspiration), and persistent or new fever, and/or lack of clinical response despite
appropriate antibiotics should heighten the suspicion for the development of a
parapneumonic effusion or an empyema.
Physical examination may identify the presence of pleural fluid with dullness on
percussion, decreased breath sounds, and decreased fremitus. Occasionally,
egophony (e-to-a sound) is present at the upper edge of the effusion. Although
decreased vocal fremitus classically differentiates a pleural effusion from lung
consolidation (associated with increased vocal fremitus), these findings are often
absent and therefore, not useful. Thus, radiographic imaging is crucial to the
complete evaluation. (See 'Diagnostic imaging' below.)
outlined by the American Association for Thoracic Surgery (AATS), the European
Association for Cardio-Thoracic Surgery (EACTS), the American College of Chest
Physician (ACCP), and the British Thoracic Society (BTS) pleural disease guideline
group (algorithm 1) [36-39].
Diagnostic imaging — Chest radiography, ultrasonography, and computed
tomography (CT) all play a key role in the evaluation and management of
parapneumonic effusions and empyema [40]. In all patients with pneumonia in whom
recent imaging has not been obtained, the chest radiograph should be the initial
imaging modality obtained for evidence of pleural fluid. Once a pleural effusion is
detected on chest radiography, ultrasonography is typically performed at the bedside
to evaluate the nature of the effusion and feasibility of sampling or drainage. CT is
generally performed when complications (eg, loculations) are suspected, complex
interventions are planned, and/or more detail of the underlying anatomy is expected
to help with management.
All three imaging modalities have their advantages and disadvantages and have
been inadequately compared. However, one retrospective analysis of 66 patients
suggested that ultrasonography was more sensitive than chest radiography (69
versus 61 percent) but less sensitive than computed tomography (69 versus 76
percent) for the diagnosis of a complicated parapneumonic effusion [41].
(See "Imaging of pleural effusions in adults".)
Magnetic resonance imaging (MRI) and positron emission tomographic scanning are
not useful, although MRI may be valuable when chest wall or spinal involvement is
suspected [42]. Their role in evaluating effusions due to malignancy is discussed
separately. (See "Imaging of pleural plaques, thickening, and tumors" and "Overview
of the initial evaluation, diagnosis, and staging of patients with suspected lung
cancer", section on 'Imaging metastatic disease'.)
Rarely, additional imaging may be required for those with empyema not associated
with pneumonia, including contrast imaging for the esophagus when a ruptured
esophagus is suspected, or CT of the abdomen when empyema due to an intra-
abdominal process (eg, liver abscess) is suspected.
Free-flowing pleural effusions accumulate in the most dependent part of the thoracic
cavity [43]. In an upright patient, some free-flowing effusions are subtle lying in a
subpulmonic location (<75 mL). Other pleural effusions can be appreciated on lateral
chest radiography as blunting of the posterior costophrenic angle (>75 mL) or on
anteroposterior chest radiography as blunting of the lateral costophrenic angle (>175
mL), while large effusions may obscure the diaphragm (>500 mL) and demonstrate a
meniscus sign. Occasionally, the entire hemithorax may be occupied by an effusion
with associated underlying lung collapse.
However, chest radiography has limitations. The meniscus sign and dependent
layering of fluid is often absent in complex/loculated parapneumonic effusions where
the radiograph may show a lenticular pleural-based opacity (image 1). In addition,
large effusions may hide underlying pneumonia and large consolidations may hide
small effusions; in both situations the threshold to obtain an ultrasound and/or chest
CT should be low. Demonstrating such limitations, in a study of 61 patients with
chest CT-proven parapneumonic effusions, anteroposterior and lateral chest
radiography missed approximately 10 percent of pleural effusions, in most cases due
to the coexistence of lower lobe consolidation [44]. Additional details regarding
radiographic characteristics of pleural effusions are discussed separately.
(See "Imaging of pleural effusions in adults", section on 'Conventional radiography'.)
In the past, lateral decubitus radiographs were often performed to determine the
extent to which an effusion is freely-flowing within the pleural space and evaluate the
safety of thoracentesis. As the availability of ultrasonography and CT advances, this
test is rarely performed. (See 'Thoracentesis and pleural fluid analysis' below.)
Air within the pleural fluid (eg, pockets or bubbles of air, gas-liquid level) may
suggest associated pneumothorax, bronchopleural fistula, air introduced during
thoracentesis, a nonexpandable lung after pleural drainage or rarely gas-producing
anaerobic organisms.
Older empyemas that have spontaneously organized and remained undetected over
years may exhibit minor or major calcification (eg, tuberculous empyema).
Distinguishing pleural fluid from pleural masses and distinguishing empyema from a
lung abscess are discussed below. (See 'Differential diagnosis' below.)
In the past, it was considered safe to sample pleural fluid when a free-flowing
effusion was demonstrated on chest radiography with at least 1 cm depth to the
chest wall on a lateral decubitus film [51]. However, most pleural effusions are now
sampled under ultrasound guidance; since there is no definition of what is
considered a “safe” amount for sampling by ultrasonography, much of this decision is
at the discretion of the ultrasonographer, although most experts would consider a
pleural space of >1 cm (between parietal and visceral pleural) safe. Occasionally, CT
guidance may be needed for sampling fluid, particularly fluid that is located in small
loculated pockets within the pleural space; in such cases, the largest and most
accessible loculation is generally chosen. A pleural fluid thickness cutoff of 2 to 2.5
cm has been suggested to guide thoracentesis by chest CT, because smaller
effusions on CT are likely to resolve with antibiotics alone [52,53].
Some studies have demonstrated that pleural fluid analysis may substantially differ
from one locule to another, limiting the value of pleural fluid analysis in this instance
[59]. Thus, in cases where the results are inconsistent with clinical findings, repeat
sampling should be considered.
Novel biomarkers of infection (eg, C-reactive protein, procalcitonin, STREM-1) in
pleural fluid have been evaluated for possible utility in distinguishing empyemas from
uncomplicated pleural effusions, but were found to be no more useful than the more
traditional pleural chemistries [60-64]. Another retrospective study showed that
higher levels of pleural vascular endothelial growth factor (VEGF) and interleukin-8
(IL-8) were associated with complicated parapneumonic effusions [63]. Further
prospective studies of serum or pleural biomarkers that define a population requiring
pleural fluid drainage are needed.
The use of the RAPID score, may help to risk-stratify patients with pleural infection
by five characteristics (renal failure, age, purulence, infectious source, and dietary
factors) and may identify those at low, medium, and high risk of mortality from a
pleural infection [69]. However, this score is not yet routinely performed.
sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Pleural effusion".)
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Term Definition
Most empyemas result from translocation of microorganisms from the alveolar space into the
pleural space in patients with pneumonia (ie, parapneumonic empyema). Less common sources of
from an abdominal focus of infection, contiguous spread from a mediastinal focus of infection, and
reactivation of infection that is dormant in the pleural space (eg, tuberculosis). The microbiology of
empyema varies considerably with the source and should be considered when selecting an empiric
antibiotic regimen.
Graphic 121168 Version 2.0
Developmental stages of parapneumonic effusion and empyema:
Diagnosis and management
age 1 Stage 2 S
cated/simple) (complicated/fibropurulent*) (complica
OR
moderate in size Generally large and free-flowing, loculated, and/or with associated pleural thickening with May be large, loculated, and/or with ple
This table displays the developmental characteristics of parapneumonic effusion and empyema.
effusions. Chest computed tomography plays a vital role in evaluating the response to therapies.
WBC: White Blood Cell; LDH: Lactate dehydrogenase; VATS: video-assisted thoracic surgery.
* A complicated parapneumonic effusion (no frank pus) or an empyema (frank pus) can present in either
stage 2 or 3 depending on pleural fluid coagulation characteristics and duration of bacterial persistence
in the pleural space. Not all patients who have a complicated parapneumonic effusion progress to
¶ Exudative uncomplicated parapneumonic effusions are generally neutrophilic and have an elevated
protein level >0.5 that of serum and/or a LDH level >0.6 that in the serum.
Δ After thoracentesis, air may be seen in the pleural space. While this may suggest trapped lung
(indicating organization), air introduced during thoracentesis and gas-producing organisms (rarely) can
◊ Complex effusions with multiple loculations may need more than one drain.
than in stage 3.
¥ Stage 3 complicated parapneumonic effusions are more likely to need VATS than stage 2 effusions.
Graphic 121162 Version 1.0
Overall prevalence
(s) Comments
range
e 10 to 20% Common cause of community-acquired pneumonia; PPE caused by S. pneumoniae are often monomicrobial.
cci 4 to 24% Common residents of oral flora; often associated with aspiration pneumonia and polymicrobial infection.
6 to 20% Common residents of oral flora; often associated with aspiration pneumonia and polymicrobial infection.
nucleatum
es
cus species
cies
10 to 15% Most common cause of hospital-acquired infections. Frequently monomicrobial and can be associated with necrotiz
and 8 to 10% Other commoncauses of hospital-acquired infections. May be monomicrobial or polymicrobial, with polymicrobial
moniae
eruginosa
This table outlines the prevalence of pathogens that commonly cause parapneumonic effusions and
uncommon causes but should be considered in endemic areas, outbreak settings, and/or in
patients with specific exposures or other risk factors. Please refer to UpToDate topic text for
additional detail.
* The prevalence of anaerobic parapneumonic effusion and empyema is difficult to accurately assess
because anaerobes are difficult to isolate in culture. Their prevalence may be underestimated,
References:
1. Marks DJ, Fisk MD, Koo CY, et al. Thoracic empyema: a 12-year study from a UK tertiary
standard methods and its mortality significance. Am J Respir Crit Care Med 2006; 174:817.
3. Davies HE, Davies RJ, Davies CW, BTS Pleural Disease Guideline Group. Management of pleural
infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65 Suppl
2:ii41.
4. Lisboa T, Waterer GW, Lee YC. Pleural infection: changing bacteriology and its implications.
5. Brook I, Frazier EH. Aerobic and anaerobic microbiology of empyema. A retrospective review in
suite. Computed tomography-guided thoracentesis may be needed when access is difficult or ultrasound
fails.
¶ Uncomplicated parapneumonic effusions are free-flowing (ie, no loculations), small to moderate size
(eg, costophrenic angle blunting only, <10 mm on lateral decubitus or estimated volume <100 mL on
imaging and, if sampled, have no evidence of bacterial involvement on culture/chemistry. They generally
resolve with antibiotics alone and typically do not need drainage, unless the effusion is symptomatic, the
patient has poor respiratory reserve, and/or the effusion is the suspected source of infection. Please
and antibiotics.
◊ Complicated parapneumonic effusions are often loculated, are typically large (ie, >half the
hemithorax, estimated volume >1000 mL) and have evidence of infection by culture or chemistry. They
generally do not resolve with antibiotics alone but, rather, need both antibiotics and drainage. Please
§ While evidence of pleural space infection by culture or chemistry is preferred for the diagnosis of
complicated parapneumonic effusion, in some cases, pleural fluid cannot be obtained, sampling is
inadequate, or patients have been pre-treated with antibiotics, thereby limiting pleural fluid analysis for
evidence of infection. In such cases, clinical findings (eg, history of probable pneumonia) and
Loculated effusion chest CT scan
CT of the chest showing a loculated pleural effusion (arrows), which is parapneumonic in origin.
The pneumonia, which is not shown here, is evident in CT cuts above this level.
Rheumatoid pleurisy
Endocrine dysfunction
Hypothyroidism
Chylous ascites
Malignant ascites
Subphrenic abscess
Miscellaneous
Pulmonary vein stenosis
Endometriosis
oma, Waldenstrom's macroglobulinemia)
Drowning
n Extramedullary hematopoiesis
ome (ARDS)
Graphic 54055 Version 10.0
Contributor Disclosures
Charlie Strange, MDEmployment: AlphaNet [Alpha-1]. Grant/Research/Clinical Trial Support:
Novartis [LAM]; Grifols [Alpha-1]; CSL Behring [Alpha-1]; Takeda [Alpha-1]; Adverum [Alpha-1];
Vertex [Alpha-1]; Arrowhead[Alpha-1]. Consultant/Advisory Boards: CSL Behring [Alpha-1];
Dicerna [Alpha-1]; Takeda [Alpha-1]; Vertex [Alpha-1].V Courtney Broaddus, MDNothing to
discloseJulio A Ramirez, MD, FACPGrant/Research/Clinical Trial Support: Pfizer [Vaccines].
Speaker's Bureau: Pfizer [Vaccines]; Medicines Company [Respiratory infections]; Amgen
[Infections in immunocompromised hosts]; Paratek [Pneumonia]. Consultant/Advisory Boards: Pfizer
[Vaccines]; Nabriva [Respiratory infections]; Medicines Company [Respiratory infections]; Paratek
[Respiratory infections]; Achaogen [Respiratory infections]; Curetis [Diagnostic tests for respiratory
infections].Geraldine Finlay, MDConsultant/Advisory Boards: LAM Board of directors, LAM
scientific grant review committee for The LAM Foundation.Sheila Bond, MDNothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
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