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Epidemiology, clinical presentation, and

diagnostic evaluation of parapneumonic effusion
and empyema in adults
Author:
Charlie Strange, MD
Section Editors:
V Courtney Broaddus, MD
Julio A Ramirez, MD, FACP
Deputy Editors:
Geraldine Finlay, MD
Sheila Bond, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2020. | This topic last updated: May 05, 2020.

INTRODUCTION A parapneumonic effusion is a pleural effusion that

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.

The epidemiology, microbiology, clinical presentation, and diagnostic evaluation of

parapneumonic effusions and empyema are reviewed here. The management of
parapneumonic effusions and empyema in adults and children is discussed
separately. (See "Management and prognosis of parapneumonic pleural effusion
and empyema in adults" and "Epidemiology, clinical presentation, and evaluation of
parapneumonic effusion and empyema in children" and "Management and prognosis
of parapneumonic effusion and empyema in children".)

DEFINITIONS A parapneumonic effusion refers to the accumulation of fluid

in the pleural space in the setting of an adjacent pneumonia (table 1).

●An uncomplicated or simple parapneumonic effusion refers to a free-
flowing effusion that is sterile.
●A complicated parapneumonic effusion refers to an effusion that has been
infected with bacteria or other micro-organisms (eg, positive Gram stain or
biochemical evidence of marked inflammation).
 ●An empyema refers to a collection of pus within the pleural space, which
can develop when pyogenic bacteria, fungi, parasites, or mycobacteria
invade the pleural space, either from an adjacent pneumonia or from direct
inoculation (eg, from blunt trauma) or other source. Empyema that
develops from an adjacent pneumonia is a subclass of a complicated
parapneumonic effusion.
●A complex effusion refers to an effusion with internal loculations.
●A uniloculated effusion is one that is without internal septae (free-flowing
or fixed).

EPIDEMIOLOGY

Incidence — Parapneumonic effusions and empyema are relatively common

complications of pneumonia. Since the advent of antibiotics, their overall incidence
has declined dramatically to approximately two to three percent of all pneumonias
[1]. However, epidemiologic studies suggest that rates are again slowly rising [2-5].
As examples, one study of 4424 patients with empyema reported an increase in the
incidence by 2.8 percent per year between the years of 1987 and 2004 [6]. Similarly,
another study of over 11,000 patients admitted to hospital with empyema found a
2.2-fold rise in the incidence of pleural infection between 1995 and 2003 in patients
<19 years and a 1.2-fold rise in patients >19 years of age [2].

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].

Risk factors — Other than risk factors for the development of pneumonia,

commonly cited risk factors for the development of a parapneumonic effusion include
aspiration, poor dental hygiene, malnutrition, and alcohol or intravenous drug abuse
[10-14]. Others include immunosuppression, age (<18 years, >65 years), partially-
treated pneumonia, and gastroesophageal reflux. (See "Overview of community-
acquired pneumonia in adults", section on 'Risk factors'.)

Prior use of inhaled glucocorticoids for chronic obstructive pulmonary disease

(COPD) or asthma has been associated with reduced incidence of parapneumonic
effusions [15], a surprising outcome given the increased incidence of community
acquired pneumonia (CAP) in these patients. The reason for this inverse association
is unknown but may be due to an altered inflammatory response from inhaled
glucocorticoids or due to a lower threshold to seek medical attention in patients with
asthma or COPD.
The presence of pre-existing pleural fluid (eg, secondary to heart failure, liver
disease) also favors growth of microorganism in the pleural space, and is likely a
contributing factor in the risk for developing pleural space infections.

PATHOGENESIS Most parapneumonic effusions and empyemas are due

to underlying pneumonia, and are believed to develop in three stages (figure 1).
Patients can present at any stage of development (table 2).

Stage 1 (simple or uncomplicated parapneumonic effusion) — Stage 1 is an

early stage of development when interstitial fluid increases during pneumonia and
moves across the adjacent visceral pleural membrane. In this stage, fluid is free-
flowing and has exudative characteristics with a protein content greater than 0.5 of
the serum value and/or a lactate dehydrogenase (LDH) level more than 0.6 than in
the serum (but usually <1000 international units [IU]/L). The white cell count is
variable but typically has neutrophilic predominance. Fluid will have a normal pH and
glucose level and no evidence to support infection with micro-organisms.
(See 'Thoracentesis and pleural fluid analysis' below.)

Stage 2 (complicated parapneumonic effusion and empyema) — Stage 2 is a

fibrinopurulent stage, whereby bacterial invasion across the damaged pleural
mesothelium stimulates an inflammatory response resulting in fibrin deposition and
loculations within the pleural space. Characteristic findings include an exudative
effusion with a high white cell count, pH <7.20, glucose <2.2 mmol/L (<40 mg/dL)
and LDH >1000 IU/L. Without pus, this is termed a complicated parapneumonic
effusion, but if frank pus is found, then this is called an empyema. Notably, it is
possible that fluid characteristics may vary among pockets of fluid/loculations.
(See 'Thoracentesis and pleural fluid analysis' below.)

Empyema can also present independently of pneumonia, when bacteria or other

pathogens directly inoculate or invade the pleural space (figure 1). In these cases,
empyema can be due to esophageal rupture, blunt or penetrating chest trauma,
hematogenous spread, mediastinitis with pleural extension, bronchogenic carcinoma
that has breached the pleura allowing bacterial translocation, infected congenital
cysts of the airway or esophagus, or extension from sources outside the thorax (eg,
liver abscess or cervical or thoracic spine infections). Postsurgical etiologies (eg,
bronchopleural fistula from lobectomy) can also be independent of pneumonia.

Stage 3 (chronic organization) — In stage 3, the pleural fluid begins to organize

[16]. In the later stages, a fibrinous pleural covering (“fibrous peel”) develops and
may encase the lung, hindering full re-expansion (trapped lung), impairing lung
function, and creating the potential for additional infection. In many cases, pleural
fluid has been organized and cannot be withdrawn for analysis. This thickened
pleura usually resolves over three to six months but in some cases forms a true scar.
(See "Diagnosis and management of pleural causes of nonexpandable lung".)
 MICROBIOLOGY Pyogenic bacteria such as Streptococcus pneumoniae,

oral streptococci and anaerobes, and Staphylococcus aureus are the most common

causes of parapneumonic effusions and parapneumonic empyema (table 3) [14,17].
Parapneumonic pleural space infections that result from community acquired
pneumonia (CAP) tend to be caused by the pyogenic bacteria that cause CAP
(eg, S. pneumoniae, S. aureus). Parapneumonic pleural space infections that result
from aspiration tend to be polymicrobial and caused by oral streptococci and
anaerobes. However, the spectrum of potential pathogens is wide and varies based
on the route of acquisition (eg, parapneumonic versus nonparapneumonic), site of
acquisition (eg, community or hospital-acquired) and geography (figure 1) [14,17,18].

For nonparapneumonic complicated pleural effusions and empyema, the list of

causative organisms is more extensive and varies considerably with the source. For
example, empyema that results from diaphragmatic translocation from an
intraabdominal infection is likely caused by gastrointestinal flora. Thus, the infection
source, local epidemiology, and patient-specific risk factors are important when
evaluating a patient with nonparapneumonic empyema.

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).

Bacteria — S. pneumoniae (pneumococcus) is the most common bacterial cause of

CAP, and among the most common causes of community-acquired parapneumonic
effusions and empyema. The reported prevalence varies among studies, ranging
from approximately 10 to 20 percent of culture-positive cases [14,19-21].
(See "Pneumococcal pneumonia in adults".)

Microaerophilic streptococci (eg, S. anginosus, S. intermedius, S. constellatus) and

anaerobes, which colonize the oropharynx, are leading causes of empyema, and
presumably reach the pleural space by spread from aspiration pneumonia
[4,14,20,22]. Empyema related to aspiration is often polymicrobial. Among
anaerobes the most frequently isolated organisms include Fusobacterium species
(eg, F. nucleatum), Prevotella species, Peptostreptococcus species,
and Bacteroides species (eg, B. melaninogenicus; B. fragilis) [8,10,23-25].
Anaerobic bacteria have been cultured in 36 to 76 percent of human empyemas
[23,26]. (See "Aspiration pneumonia in adults", section on
'Microbiology' and "Anaerobic bacterial infections" and "Anaerobic bacterial
infections", section on 'Pleuropulmonary infections'.)

Staphylococcus aureus accounts for approximately 10 to 15 percent of

parapneumonic effusions and empyema overall [14,17,20]. The prevalence of S.
aureus is highest among hospital-acquired empyemas (accounting for approximately
one-third of cases), but S. aureus empyema can also occur secondary to CAP.
Gram-negative rods, including Escherichia coli, other
Enterobacteriaceae, Pseudomonas aeruginosa, and Klebsiella species, collectively
account for approximately 8 to 10 percent of cases [14,20].
Atypical bacteria, such as Legionella, Mycoplasma, and Chlamydia species, are rare
but reported causes of parapneumonic effusions and empyema. (See "Clinical
manifestations and diagnosis of Legionella infection" and "Mycoplasma pneumoniae
infection in adults" and "Mycoplasma pneumoniae infection in adults", section on
'Pneumonia'.)

The relative prevalence of pathogens also varies with geography. As an

example, Burkholderia pseudomallei is endemic in Southeast Asia, South Asia, and
northern Australia. In areas of high prevalence, such as Thailand, B. pseudomallei is
a common cause of pneumonia, and has been reported to cause up to 20 percent of
pleural infections [27]. (See "Melioidosis: Epidemiology, clinical manifestations, and
diagnosis".)

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.  

Mycobacteria — Mycobacterial effusion and empyema are considerably less

frequent than bacterial empyema, and usually result from reactivation of latent
tuberculosis (TB) in the subjacent lung or pleural space. Tuberculous empyema
should be considered in patients who live in an endemic area and/or who have risk
factors for TB. [30]. Tuberculous empyema, in which the TB organism can be found
by stain or by culture in the pleural effusion, should be differentiated from
tuberculous pleurisy in which a lymphocytic effusion occurs from the immunologic
response to tuberculous proteins and the TB organisms are few and only reliably
found in the pleural tissue. Further details regarding the manifestations of
tuberculous empyema are discussed separately. (See "Tuberculous pleural
effusion".)

Less commonly, atypical mycobacteria are also associated with parapneumonic

effusion and empyema, (eg, Mycobacterium abscessus, Mycobacterium avium,
Mycobacterium kansasii) [31]. (See "Overview of nontuberculous mycobacterial
infections in HIV-negative patients".)

Other pathogens — Fungal pleural infection is rare (<1 percent of cases)

with Candida species being responsible for the majority of cases [32]. Candida
pneumonia and empyema typically occur in the setting of disseminated infections in
highly immunocompromised patients or, in the case of empyema, as a complication
of thoracic surgery [32]. Aspiration of Candida from the oropharynx is unlikely to
cause either pneumonia or empyema. (See "Candida infections of the abdomen and
thorax".)

Less commonly reported fungal pleural infections are caused by cryptococcus

and Aspergillus species, both of which most often occur in immunocompromised
hosts [32,33].
Parasites are rare causes of pleural infections, but Entamoeba
histolytica, Echinococcus granulosus and Paragonimus westermani can cause
pleural effusions [34,35].

Viruses do not typically cause empyema. However, secondary bacterial infections

can complicate viral pneumonias. As an example, in patients with influenza, the
major causes of bacterial superinfection and empyema have been Staphylococcus
aureus, Streptococcus pneumoniae, and Staphylococcus pyogenes [29].

CLINICAL FEATURES The clinical findings of a parapneumonic effusion

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.

History and examination — Common clinical features on history include cough,

fever, pleuritic chest pain, dyspnea, and sputum production. Compared with those
with pneumonia alone or pneumonia with simple parapneumonic effusion, patients
with empyema may report a longer course with several days of fever and malaise,
with one trial reporting duration of symptoms as long as two weeks [7]. Presentation
may also be more insidious and delayed in patients with anaerobic infections (eg,
those with aspiration, poor dental hygiene) with some patients presenting with loss of
appetite and weight loss over weeks to months [10-12].

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.)

Laboratory findings — There are no specific laboratory blood tests that are

diagnostic of a parapneumonic effusion. Laboratory findings usually reflect that of
infection such as leukocytosis, left shift, elevated C-reactive protein. In some cases,
bacteremia can co-occur and the infecting organism can be identified from blood
cultures (up to 12 percent of cases) [7]. (See "Diagnostic approach to community-
acquired pneumonia in adults".)

DIAGNOSTIC EVALUATION Our approach is generally similar to that

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.

Chest radiography — Most parapneumonic effusions or empyemas are initially

suspected during the routine evaluation of patients with suspected or known
pneumonia.

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.)

Ultrasonography — Free-flowing or loculated pleural effusions as well as

underlying consolidation or solid masses can be appreciated on chest
ultrasonography. Ultrasonography is now typically performed at the bedside for most
pleural effusions to evaluate the size and characteristics of the effusions. Although
ultrasonography is best utilized for selecting and guiding needle or catheter
placement for thoracentesis, it also provides important prognostic and therapeutic
information [45]. Data that support the use of pleural ultrasonography are discussed
separately. (See "Bedside pleural ultrasonography: Equipment, technique, and the
identification of pleural effusion and pneumothorax", section on 'Identification of
pleural effusion using ultrasonography' and "Ultrasound-guided thoracentesis".)

Chest computed tomography — Chest CT (typically with intravenous contrast to

help identify the pleural membranes) is the most sensitive method for detecting small
amounts of pleural fluid (>2 mL). CT can also easily appreciate loculations (image 2)
and underlying airway, pleural, and parenchymal abnormalities (eg, pneumonia,
abscess, fistulae, diaphragmatic defects, esophageal rupture, or masses that
suggest underlying cancer) as well as chest tube positioning [46-48].

During the fibrinopurulent and organizing stages of complicated parapneumonic

effusions and empyema (see 'Pathogenesis' above), radiographic contrast
enhancement of the pleural surfaces assists in delineating pleural fluid loculations
and in characterizing empyema. As examples:

●Loculations, often lenticular in shape, may be appreciated by tapered

borders and obtuse angles between the fluid and the chest wall with an
absence of the meniscus sign.
●Parietal pleural thickening is seen in 86 percent and pleural enhancement
in 96 percent of patients with empyema [47]. Thickening of the visceral and
parietal pleura is suggestive of empyema when associated with significant
(usually >30 mm) separation of the pleural surfaces (split pleura sign),
which can be appreciated in up to 68 percent of patients [47,49].
●Pleural infection is also associated with increased attenuation of
extracostal fat [47].

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.)

Thoracentesis and pleural fluid analysis — Most cases of suspected

parapneumonic effusion or empyema should at minimum be sampled unless the
effusion is too small or sampling is deemed unsafe [50]. Results guide further
management of the effusion. Diagnostic thoracentesis is typically performed under
ultrasound guidance. In some cases, therapeutic thoracentesis is simultaneously
performed when symptomatic relief is needed or when drainage is indicated (eg,
frank pus is observed). Indications and contraindications and technique for
thoracentesis are discussed separately. (See "Ultrasound-guided
thoracentesis" and "Bedside pleural ultrasonography: Equipment, technique, and the
identification of pleural effusion and pneumothorax".)  

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].

Fluid obtained by thoracentesis should be sent for the following:

●Cell count with differential and chemistries – A total protein, lactate

dehydrogenase (LDH), and glucose should be obtained together with
serum values for protein and LDH. A neutrophil predominance is more
common in patients with bacterial pneumonia while a lymphocyte
predominance may indicate tuberculous or fungal etiologies. Distinguishing
exudates from transudates is discussed separately. (See "Diagnostic
evaluation of a pleural effusion in adults: Initial testing", section on 'Pleural
fluid analysis'.)
●Microbiologic analysis – Microbiologic analysis of the pleural fluid with
appropriate stains and cultures (eg, aerobic, anaerobic, mycobacterial,
fungal) is critical. Although sampling should ideally occur before the
administration of antibiotics, thoracentesis should not delay prompt
antimicrobial therapy. Samples should be drawn directly from the pleural
space because cultures from previously placed catheters or tubing can be
colonized or contaminated with bacteria or fungi [54].
Pleural fluid should be inoculated directly into blood culture bottles (aerobic
and anaerobic) in addition to the usual sterile containers used for standard
Gram stain and culture, in order to maximize diagnostic yield [55,56]. In a
series of 53 patients with suspected pleural infection and culture data from
both standard and blood culture bottles obtained at the same time, the
number of patients with identifiable pathogens increased by 21 percent
 (95% CI 8.9 to 20.8 percent) [53]. A sterile container without culture media
is acceptable if only a small amount of fluid is available.
A putrid odor of fluid is considered diagnostic of anaerobic infection; the
Gram stain will also help identify anaerobes because of the unique
morphology of some anaerobic Gram-negative rods. (See "Anaerobic
bacterial infections" and "Pathophysiology, clinical clues, and recovery of
organisms in anaerobic infections".)
Blood and pleural culture results yield a diagnosis in approximately 60
percent of cases [20]. There are several reasons why bacteria may not be
identified in culture for the remaining 40 percent:
•Anaerobic organisms may be difficult to culture
•Anaerobic cultures are not specifically requested
•Sampling is often performed after a patient has received antibiotics
•Sterile inflammatory fluid may be aspirated adjacent to an infected
loculus of infection
•Current culture methods are insufficiently sensitive
•Bacteria may be located in the pleural membranes rather than in the
fluid [57]
Some centers have begun routine molecular analysis of parapneumonic
effusions to detect S. pneumoniae infection by rapid antigen detection
assays or broad-range 16S ribosomal DNA polymerase chain reaction.
These centers report a much higher detection rate for S. pneumoniae than
historical case series [58].  
Special stains and cultures should be requested when unusual organisms
or organisms that require special culture conditions are suspected.
●pH – The pH should be drawn directly into an arterial blood gas syringe
and determined with a blood gas analyzer within one hour of sampling.
Residual lidocaine and heparin falsely decrease the pH and air in the
syringe falsely increases the pH; therefore, the same needle that is used to
anesthetize the pleural space should not collect the pH sample. It is not
necessary to run the sample through an analyzer if frank pus is collected
since that feature is diagnostic of an empyema. (See "Diagnostic
evaluation of a pleural effusion in adults: Initial testing".)
The pH is the most useful test when determining the therapeutic course,
the details of which are discussed separately. (See 'Complicated
parapneumonic effusion and empyema' below and "Management and
prognosis of parapneumonic pleural effusion and empyema in adults".)  
The differential diagnosis of pleural fluid acidosis, a feature typically
associated with a complicated parapneumonic effusion or empyema is
discussed below. (See 'Differential diagnosis' below.)
●Cytology – Cytologic examination for appropriate stains (eg,
mycobacteria, actinomyces, nocardia) can be sent when organisms
requiring special stains are needed. In addition, malignancy can cause
pleural fluid acidosis; thus, sending fluid for cytology for malignant cells is
prudent.  

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.

Other tests — Although blood cultures are frequently negative in patients with

parapneumonic effusion and empyema, they should be obtained. Growth from
cultures can help make the microbiologic diagnosis as well as identify concurrent
bacteremia. The need for additional microbiologic testing should be determined on a
case-by-case basis (eg, sputum cultures, urine S. pneumoniae antigen testing,
interferon-gamma release assays for tuberculosis, galactomannan, cryptococcal
antigen).

Procalcitonin’s usefulness for distinguishing bacterial from nonbacterial

parapneumonic effusions is not well studied, but is not likely to be high. In one study,
serum procalcitonin levels >0.18 ng/mL were associated with a sensitivity of 83
percent and specificity of 81 percent for the pleural effusion having a bacterial
infectious etiology [62]. However, this marker rises in the setting of invasive and
systemic infections; thus the sensitivity for determining whether bacteria are present
in a contained space infection is questionable. Neither high nor low procalcitonin
levels are likely to change the need for drainage. (See "Procalcitonin use in lower
respiratory tract infections", section on 'Procalcitonin biology'.)

DIFFERENTIAL DIAGNOSIS Several conditions need to be entertained

when evaluating a suspected parapneumonic effusion or empyema.

●Pleural fluid exudates – The differential diagnosis of an exudative pleural
effusion is listed in the table (table 4). Further studies may be needed on
pleural fluid or pleural biopsy may be required to distinguish these from
one another, the details of which are discussed separately.
(See "Diagnostic evaluation of a pleural effusion in adults: Initial testing".)
●Pleural fluid acidosis – Pleural fluid acidosis and/or low glucose, although
highly suspicious for a complicated parapneumonic pleural effusion or
empyema, can be associated with other diseases including malignancy,
tuberculosis, rheumatoid pleuritis, lupus pleuritis, and urinothorax [65]. It
may also be seen in patients who have a central venous catheter that is
misplaced in the pleural space and is infusing isotonic fluid such as saline.
These conditions can be excluded when clinically indicated with
appropriate serology or further analysis of the pleural fluid. Pleural space
infections caused by urease-splitting organisms such as Proteus species
may result in a spuriously elevated pleural pH [66]. (See "Pleural effusion
of extra-vascular origin (PEEVO)".)
●Pleural effusion or masses on imaging – Distinguishing loculated pleural
fluid from a pleural mass on chest radiography or computed tomography
(CT) can be challenging but differences in the CT attenuation can help
 distinguish fluid from solid masses. However, if organization is advanced,
occasionally, a pleural biopsy will be needed to assure that pleural based
malignancy is excluded.  
Chest CT can also help distinguish a lung abscess from empyema.
Empyemas are more likely to compress adjacent lung rather than erode it,
whereas lung abscesses are more likely to erode adjacent structures.
Empyemas typically have thinner, smoother walls than lung abscesses,
which tend to have thicker walls and irregular luminal and exterior
surfaces. Empyemas tend to form an obtuse angle of interface with the
chest wall, compared with lung abscesses, which commonly have an acute
angle, although this feature is nonspecific. (See "Imaging of pleural
effusions in adults", section on 'Computed tomography'.)

DIAGNOSIS In most patients, the diagnosis of a parapneumonic effusion

and empyema is made by a constellation of clinical signs and symptoms with

confirmatory chemical and microbiologic data from pleural fluid (table
2 and algorithm 1). Rarely, a complicated parapneumonic effusion or empyema
requires definitive diagnosis on pleural biopsy, most often by thoracoscopy, when
micro-organisms are demonstrated in or cultured from affected pleural tissue.
Occasionally, a retrospective diagnosis may be made when patients present in the
late stages of organization (ie, stage 3 (see 'Pathogenesis' above)) and fibrous peel
is identified during thoracoscopy that requires decortication.

Uncomplicated parapneumonic effusion — A parapneumonic effusion is

considered uncomplicated or simple when:
●The pleural effusion is free-flowing and too small to sample
●A free-flowing small effusion has a neutrophilic exudate (an elevated
protein level >0.5 percent of serum and/or a lactate dehydrogenase (LDH)
level >0.6 that in the serum), a normal pH, a normal glucose level, and
does not contain micro-organisms  

In most cases, uncomplicated parapneumonic effusions resolve with appropriate

antibiotic therapy and drainage is not generally necessary. However, the threshold to
repeat imaging and obtain pleural fluid sampling should be low if patients do not
respond adequately to antimicrobial therapy. (See "Management and prognosis of
parapneumonic pleural effusion and empyema in adults", section on 'Uncomplicated
parapneumonic effusion (antibiotics alone)'.)

Complicated parapneumonic effusion and empyema — A parapneumonic

effusion is considered complicated when an exudative effusion has any one or more
of the following characteristics: has a pH <7.2 and/or contains evidence of micro-
organism invasion by culture or Gram stain. In the absence of pH data, a low
glucose level <40 mg/L may be used instead. Although a serum LDH >1000
international units (IU)/L may support the diagnosis, it is non-specific and may simply
indicate infection or significant inflammation elsewhere. It is typically large, loculated,
or has associated pleural thickening. When it is bacterial, it generally contains a
large number of neutrophils. For several reasons, cultures of fluid from complicated
parapneumonic effusions are sometimes negative. Although a positive culture is
confirmatory, this is not necessary for the diagnosis [67]. An empyema (due to
pneumonia) is a complicated parapneumonic effusion in which frank pus is seen on
pleural fluid sampling. (See 'Thoracentesis and pleural fluid analysis' above.)

In most cases of complicated parapneumonic effusion, drainage is indicated. Pleural

pH <7.2 is the most useful predictor of a complicated clinical course [68]. If pleural
pH is not measured, a pleural fluid glucose value <40 mg/dL and/or pleural fluid LDH
value >1000 IU/L, or significant loculations are also predictive of the need for tube
thoracostomy [68]. Empyema is an absolute indication for chest tube drainage.
(See "Management and prognosis of parapneumonic pleural effusion and empyema
in adults", section on 'Complicated pleural effusion and empyema (antibiotics plus
drainage)'.)

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.

SOCIETY GUIDELINE LINKS Links to society and government-

sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Pleural effusion".)

SUMMARY AND RECOMMENDATIONS

●A parapneumonic effusion is a pleural effusion that forms in the pleural

space adjacent to a pneumonia. When bacteria or other pathogens infect
the pleural space, a complicated parapneumonic effusion or empyema
may result. Parapneumonic effusions and empyema are common
complications of pneumonia but an empyema can also develop without the
presence of an adjacent pneumonia. The incidence is approximately two to
three percent of all pneumonias but appears to be rising.
(See 'Introduction' above and 'Epidemiology' above.)
●Parapneumonic effusion and empyema may be part of a developmental
spectrum that includes three stages (table 2). Stage 1 is typically an early
stage where fluid is free-flowing and small, such that resolution occurs with
antibiotics alone. In some cases, patients will progress to stage 2, a
fibrinopurulent stage where infection precipitates organization and
loculations. Stage 3 is characterized by a thickened fibrinous coating that
may limit lung expansion. (See 'Pathogenesis' above.)
●The microbiology of complicated pleural effusions and empyema vary with
source of infection, route of acquisition, local epidemiology and patient-
specific risk factors (table 3). Parapneumonic pleural space infections
typically result as complications of community acquired pneumonia (CAP)
or aspiration pneumonia. Those associated with CAP tend to be caused by
the pyogenic bacteria that cause CAP (eg, S. pneumoniae and S. aureus)
whereas those associated with aspiration pneumonia tend to be
polymicrobial and caused by oral streptococci and anaerobes. The list of
pathogens associated with nonparapneumonic pleural space infections is
more extensive and varies by source. (See 'Microbiology' above.)
●The clinical findings of a parapneumonic effusion and empyema are
nonspecific and, with the exception of decreased fremitus, overlap with
those of pneumonia. Among patients with pneumonia, the presence of risk
factors (eg, aspiration, poor dental hygiene, alcohol or intravenous drug
abuse, immunosuppression, young or old age, partially-treated pneumonia,
and gastroesophageal reflux) and the development of a persistent or new
fever despite appropriate antibiotics should heighten the suspicion for the
development of a parapneumonic effusion or an empyema. (See 'Clinical
features' above and 'Risk factors' above.)
●In all patients with pneumonia, the imaging modality that defined the
pneumonia should be re-examined for evidence of pleural fluid. Once a
pleural effusion is suspected on chest radiography, ultrasonography is
typically performed at the bedside to evaluate the nature of the effusion
and feasibility of sampling or drainage. Computed tomography is generally
additionally 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. (See 'Diagnostic
imaging' above.)
●Most cases of suspected parapneumonic effusion or empyema should be
sampled under ultrasound guidance unless the effusion is too small or
sampling is deemed unsafe. In some cases, therapeutic thoracentesis is
simultaneously performed when symptomatic relief is needed or when
drainage is indicated (eg, frank pus is observed). Fluid should be sent for
cell count and differential, chemistries (protein and lactate dehydrogenase
[LDH]), Gram stain and culture with additional inoculation of fluid into blood
culture bottles (aerobic and anaerobic), pH (drawn directly into an arterial
blood gas syringe and analyzed within one hour), and cytology. Special
stains and cultures should be requested when unusual organisms or
organisms that require special culture conditions are suspected.
(See 'Thoracentesis and pleural fluid analysis' above.)  
●Several conditions need to be entertained when evaluating a suspected
parapneumonic effusion or empyema including other causes of an
exudative effusion (table 4), pleural fluid acidosis (eg, malignancy,
tuberculosis, rheumatoid pleurisy, lupus pleuritis, urinothorax, or
infused saline), and pleural masses or lung abscesses. (See 'Differential
diagnosis' above.)
●In most patients, the diagnosis of a parapneumonic effusion and
empyema is made by a constellation of clinical signs and symptoms with
confirmatory chemical and microbiologic data from pleural fluid (table 2). It
is rare that pleural biopsy is required. In general, we and others categorize
parapneumonic effusions as the following (see 'Diagnosis' above):
•A parapneumonic effusion is considered uncomplicated
(simple) when the effusion is free-flowing and too small to sample or
when a small free-flowing effusion has a neutrophilic exudate (an
elevated protein level >0.5 that in serum and/or a LDH level > 0.6 that
in serum) with normal pH and glucose levels and does not contain
micro-organisms. These effusions typically resolve with antibiotics
 although the threshold to reimage should be low to look for disease
progression.
•A parapneumonic effusion is considered complicated when an
exudative effusion has any one or more of the following
characteristics: has a pH <7.2 (or a low glucose level <40 mg/L in the
absence of pH data), and/ or contains evidence of micro-organism
invasion by culture or Gram stain. It is typically large, loculated, and
has associated pleural thickening. An empyema is considered present
when frank pus is seen on pleural fluid sampling.
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Topic 6702 Version 43.0

GRAPHICS
Parapneumonic effusion and empyema terminology

Term Definition

ic effusion Fluid in the pleural space in the setting of an adjacent pneumonia

d (simple) parapneumonic effusion Free-flowing effusion that is sterile

parapneumonic effusion Effusion infected with bacteria or other micro-organisms or having biochemical properties suggestive of recent infection

Pus in the pleural space (from pneumonia or other source)

sion Effusion with internal loculations (septae)

effusion Effusion that is without internal septae (free-flowing or fixed)

Graphic 121161 Version 1.0

Potential sources of empyema

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

empyema include hematogenous spread, direct pleural inoculation, diaphragmatic translocation

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

Late (days to weeks) Late (weeks to months)

istics¶ Exudative characteristics¶ Fluid may be difficult to obtain

elevated WBC High WBC Bacterial organisms may or may not be

ternational units/L LDH >1000 international units/L

ose levels pH <7.20

ms Glucose <40 mg/dL (2.2 mmol/L)

OR

Bacterial organisms present

moderate in size Generally large and free-flowing, loculated, and/or with associated pleural thickening with May be large, loculated, and/or with ple

contrast enhancement demonstrate a pleural rind)

Pleural calcification may be evidentΔ

with antibiotic therapy Antibiotics PLUS drainage◊ Antibiotics PLUS drainage

Fibrinolytics/DNase may be required§ Fibrinolytics/mucolytics or VATS may

This table displays the developmental characteristics of parapneumonic effusion and empyema.

Prompt diagnosis and treatment is essential to the successful management of parapneumonic

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

empyema. Importantly, while the identification of micro-organisms is helpful, abnormal chemistries

alone are generally sufficient for the diagnosis.

¶ 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

also cause this finding.

◊ Complex effusions with multiple loculations may need more than one drain.

§ Complicated parapneumonic effusions tend to be more responsive to fibrinolytics/DNase in stage 2

than in stage 3.

¥ Stage 3 complicated parapneumonic effusions are more likely to need VATS than stage 2 effusions.
 Graphic 121162 Version 1.0

Prevalence of pathogens causing parapneumonic effusions and

empyema

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

aspiration pneumonia. Pseudomonas may be associated with necrotizing or cavitary pneumonia.

moniae

eruginosa

This table outlines the prevalence of pathogens that commonly cause parapneumonic effusions and

parapneumonic empyema. Other organisms, such as Mycobacteria tuberculosis, Burkholderia

pseudomallei, atypical pathogens (eg, Legionella and Mycoplasma species) and fungi are

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,

particularly as components of polymicrobial infections.

References:

1. Marks DJ, Fisk MD, Koo CY, et al. Thoracic empyema: a 12-year study from a UK tertiary

cardiothoracic referral centre. PLoS One 2012; 7:e30074.

2. Maskell NA, Batt S, Hedley EL, et al. The bacteriology of pleural infection by genetic and

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.

Respirology. 2011; 16:598.

5. Brook I, Frazier EH. Aerobic and anaerobic microbiology of empyema. A retrospective review in

two military hospitals. Chest 1993; 103:1502.

Graphic 121163 Version 2.0

Characterization of a pleural effusion in patients with pneumonia

* Thoracentesis is typically ultrasound-guided and can be performed at the bedside or in a radiology

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

refer to the UTD topic for further details.

Δ An empyema is defined by the presence of pus in the pleural space and requires immediate drainage

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

refer to the UTD topic for further details.

§ 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

radiographic imaging is used to make a diagnosis of "probable" or "likely" complicated parapneumonic

effusion and are generally treated as such.

Graphic 122289 Version 1.0

Parapneumonic effusion chest radiograph

Chest radiograph showing loculated right parapneumonic effusion.

Courtesy of Charlie Strange, MD.

Graphic 73968 Version 3.0

Normal chest radiograph

Posteroanterior view of a normal chest radiograph.

Courtesy of Carol M Black, MD.

Graphic 65576 Version 5.0

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.

CT: computed tomography.

Courtesy of Charlie Strange, MD.

Graphic 80445 Version 5.0

Causes of exudative pleural effusions

Increased negative intrapleural pressure with a

malignancy or inflammation
Lung entrapment
 Cholesterol effusion (eg, due to tuberculosis, rheumatoid

Connective tissue disease

coplasma) Lupus pleuritis

Rheumatoid pleurisy

Mixed connective tissue disease

Eosinophilic granulomatosis with polyangiitis (Churg-St

Granulomatosis with polyangiitis (Wegener's)

Familial Mediterranean fever

Endocrine dysfunction
Hypothyroidism

Ovarian hyperstimulation syndrome

ement/migration Lymphatic abnormalities

n, dantrolene, methysergide, dasatinib, amiodarone, Malignancy
hotrexate, clozapine, phenytoin, beta blocker, ergot drugs)
Chylothorax (eg, yellow nail syndrome, lymphangioleiom

Movement of liquid from abdomen to pleural sp

Pancreatitis
pace
Pancreatic pseudocyst
monary neoplasms
Meigs' syndrome

Chylous ascites

Malignant ascites

Subphrenic abscess

Hepatic abscess (bacterial, amebic)

Splenic abscess, infarction

Miscellaneous
Pulmonary vein stenosis

Endometriosis
oma, Waldenstrom's macroglobulinemia)
 Drowning

ers Electrical burns

Capillary leak syndrome

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

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