Epidemiology, Clinical Presentation, and Diagnostic Evaluation of Parapneumonic Effusion and Empyema in Adults - UpToDate

Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults - UpToDate 25/10/22 16:31
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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: Sep 2022. | This topic last updated: Jun 14, 2022.
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
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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 microorganisms (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 penetrating
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]. Continued increases have been noted from 2008 to
2018 in the United Kingdom, particularly in those aged >60 years, with a seasonal
variability associated with influenza infections [7].
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 [8-10].
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 [11-15]. Others
include immunosuppression, age (<18 years, >65 years), partially-treated pneumonia,
influenza [7], 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 [16], 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 preexisting 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 microorganisms. (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 [17]. In
the later stages, a fibrinous pleural covering ("fibrous peel") develops and may encase the
lung, hindering full reexpansion (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) [15,18]. 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)
[15,18,19].
For nonparapneumonic complicated pleural effusions and empyema, the list of causative
organisms is more extensive and varies considerably with the source ( figure 2). 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 [15,20-22]. (See "Pneumococcal
pneumonia in patients requiring hospitalization", section on 'Pleural effusion and
empyema'.)
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 [4,15,21,23].
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) [9,11,24-26]. Anaerobic bacteria have been cultured in 36 to 76 percent of human
empyemas [24,27]. (See "Aspiration pneumonia in adults", section on 'Microbiology' and
"Anaerobic bacterial infections".)
Staphylococcus aureus accounts for approximately 10 to 15 percent of parapneumonic

effusions and empyema overall [15,18,21]. 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 [15,21].
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 [28]. (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
[29]. In patients with influenza, the major causes of bacterial superinfection and empyema
have been Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes
[30]. 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. [31].
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) [32]. (See "Overview of nontuberculous mycobacterial infections".)
Other pathogens — Fungal pleural infection is rare (<1 percent of cases) with Candida
species being responsible for the majority of cases [33]. 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 [33]. 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 [33,34].
Parasites are rare causes of pleural infections, but Entamoeba histolytica, Echinococcus
granulosus and Paragonimus westermani can cause pleural effusions [35,36].
Viruses do not typically cause empyema. For example, no influenza viruses were
detectable by polymerase chain reaction in any pleural fluid samples in a prospective
study evaluating pleural space infections following influenza [7]. 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 Streptococcus pyogenes [30].
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 [8]. 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 [11-13].
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) [8]. (See "Clinical evaluation and diagnostic testing for 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) [37-40].
Diagnostic imaging — Chest radiography, ultrasonography, and computed tomography

(CT) all play a key role in the evaluation and management of parapneumonic effusions and
empyema [41]. 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 [42]. (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
[43]. 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
'Clinical-directed imaging'.)
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 intraabdominal process (eg,
liver abscess) is suspected ( figure 2).
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 [44]. 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 [45]. 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 [46]. 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 [47-49].
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.
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● Parietal pleural thickening is seen in 86 percent and pleural enhancement in 96

percent of patients with empyema [48]. 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 [48,50].
● Pleural infection is also associated with increased attenuation of extracostal fat [48].
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 [51]. 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 [52]. 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 [53,54].
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 [55].
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 [56,57]. 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) [54]. 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 [21]. 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 [58]
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 [59].
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 [60]. 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 [61-65]. 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 [64]. 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 [63]. 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 [66]. 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 [67]. (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 microorganisms 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 microorganisms.
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 microorganism invasion by
culture or Gram stain. In the absence of pH data, a low glucose level <40 mg/dL 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 [68]. 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 [69]. 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 [69].
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 [70].
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
● Definition and epidemiology – A parapneumonic effusion is a pleural effusion that

forms in the pleural space adjacent to a pneumonia ( table 1). 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.)
● Pathogenesis – Parapneumonic effusion and empyema may be part of a

developmental spectrum that includes three stages ( table 2). Not every patient
progresses through each stage.
• Stage 1 is typically an early stage where fluid is free-flowing and small, such that
resolution occurs with antibiotics alone.
• Stage 2 is 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.)
● Microbiology – The microbiology of complicated pleural effusions and empyema

vary with source of infection ( figure 1), route of acquisition, local epidemiology,
and patient-specific risk factors ( table 3). (See 'Microbiology' above.)
• Parapneumonic – 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, Streptococcus pneumoniae and Staphylococcus aureus). In contrast, those
associated with aspiration pneumonia tend to be polymicrobial and caused by
oral streptococci and anaerobes.
• Non-parapneumonic – The list of pathogens associated with non-

parapneumonic pleural space infections is more extensive and varies by source
( figure 1).
● Suspecting parapneumonic effusion – 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. The clinical findings of a parapneumonic
effusion and empyema are nonspecific and, with the exception of decreased
fremitus, overlap with those of pneumonia. (See 'Risk factors' above and 'Clinical
features' above.)
● Imaging – In all patients with pneumonia, the imaging modality that defined the
pneumonia should be reexamined 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.)
● Thoracentesis – 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. (See 'Thoracentesis and pleural fluid analysis' above.)
• 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.
● Differential diagnosis – 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.)
● Diagnosis and classification – 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):
• Uncomplicated – 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 microorganisms. These effusions typically
resolve with antibiotics, although the threshold to reimage should be low to look
for disease progression.
• Complicated – 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/dL in the absence of pH data) and/ or contains
evidence of microorganism invasion by culture or Gram stain. It is typically large,
loculated, and has associated pleural thickening.
• Empyema – An empyema is considered present when frank pus is seen on

pleural fluid sampling.
Use of UpToDate is subject to the Terms of Use.
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Topic 6702 Version 53.0
GRAPHICS
Parapneumonic effusion and empyema terminology
Term Definition
Parapneumonic effusion Fluid in the pleural space in the setting of an adjacent pneumonia
Uncomplicated (simple) Free-flowing effusion that is sterile

parapneumonic effusion
Complicated Effusion infected with bacteria or other micro-organisms or

parapneumonic effusion having biochemical properties suggestive of recent infection
Empyema Pus in the pleural space (from pneumonia or other source)
Complex effusion Effusion with internal loculations (septae)
Uniloculated 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.
Developmental stages of parapneumonic effusion and empyema:

Diagnosis and management
Stage 1 Stage 2 Stag

Stage
(uncomplicated/simple) (complicated/fibropurulent*) (complicated/
Timing Early (days) Late (days to weeks) Late (weeks to mo
Pleural fluid Exudative characteristics ¶ Exudative characteristics ¶ Fluid may be diffi

characteristics
Low to moderately elevated High WBC Bacterial organism
WBC not be present
LDH >1000 international units/L
LDH level <1000
pH <7.20
international units/L
Glucose <40 mg/dL (2.2 mmol/L)
Normal pH and glucose
levels OR
No bacterial organisms Bacterial organisms present
Imaging Generally small to moderate Generally large and free-flowing, May be large, loc
characteristics in size loculated, and/or with associated with pleural thick
pleural thickening with contrast extensive and dem
Free-flowing
enhancement pleural rind)
Pleural calcificatio
evident Δ
Treatment Typically resolves with Antibiotics PLUS drainage ◊ Antibiotics PLUS d

antibiotic therapy alone
Fibrinolytics/DNase may be Fibrinolytics/muc
Drain if symptomatic required § may be required
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.
Prevalence of pathogens causing parapneumonic effusions and

empyema
Overall
Typical setting Pathogen(s) prevalence Comments
range
Community- Streptococcus 10 to 20% Common cause of

acquired pneumoniae community-acquired
pneumonia; PPE
caused by S.
pneumoniae are
often
monomicrobial.
Microaerophilic 4 to 24% Common residents

streptococci of oral flora; often
S. intermedius associated with
S. anginosus aspiration
pneumonia and
S. constellatus
polymicrobial
infection.
Anaerobes, including*: 6 to 20% Common residents

Fusobacterium of oral flora; often
nucleatum associated with
Prevotella species aspiration
pneumonia and
Peptostreptococcus
polymicrobial
species
infection.
Bacteroides
species
Hospital-acquired Staphylococcus aureus 10 to 15% Most common cause

of hospital-acquired
infections.
Frequently
monomicrobial and
can be associated
with necrotizing or
cavitary pneumonia.
Gram-negative 8 to 10% Other common

anaerobes and aerobes causes of hospital-
including: acquired infections.

Escherichia coli May be
Klebsiella monomicrobial or
pneumoniae polymicrobial, with
polymicrobial
Pseudomonas
infection more likely
aeruginosa
if associated with
aspiration
pneumonia.
Pseudomonas may
be associated with
necrotizing or
cavitary pneumonia.
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.
Parapneumonic effusion
Extrapulmonary sources of pleural space infections can occur hematogenously

or through direct proximity to the pleural space. Common sources include
esophageal perforation and intraabdominal infections.
* Biliopleural fistulae can produce sterile pleural space infections from the
inflammatory effects of bile.
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.
Parapneumonic effusion chest radiograph
Chest radiograph showing loculated right parapneumonic effusion.
Courtesy of Charlie Strange, MD.
Normal chest radiograph
Posteroanterior view of a normal chest radiograph.
Courtesy of Carol M Black, MD.
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.
Causes of exudative pleural effusions
Infectious Increased negative intrapleural

pressure with accompanying pleural
Bacterial pneumonia
malignancy or inflammation
Tuberculous pleurisy
Lung entrapment
Parasites
Cholesterol effusion (eg, due to
Fungal disease
tuberculosis, rheumatoid arthritis)
Viral pneumonias (eg, influenza,
Connective tissue disease
coronavirus disease 2019 [COVID-19])
Lupus pleuritis
Nocardia, Actinomyces
Rheumatoid pleurisy
Subphrenic abscess
Mixed connective tissue disease
Hepatic abscess
Eosinophilic granulomatosis with
Splenic abscess
polyangiitis (Churg-Strauss)
Hepatitis
Granulomatosis with polyangiitis
Spontaneous esophageal rupture (Wegener's)
Cholecystitis Familial Mediterranean fever
Iatrogenic or trauma Endocrine dysfunction

Central venous catheter Hypothyroidism
misplacement/migration
Ovarian hyperstimulation syndrome
Drug-induced (eg, nitrofurantoin,
dantrolene, methysergide, dasatinib, Lymphatic abnormalities
amiodarone, interleukin-2, procarbazine, Malignancy
methotrexate, clozapine, phenytoin, beta
blocker, ergot drugs) Chylothorax (eg, yellow nail syndrome,
lymphangioleiomyomatosis,
Esophageal perforation lymphangiectasia)
Esophageal sclerotherapy
Movement of liquid from abdomen
Enteral feeding tube in pleural space to pleural space
Radiofrequency ablation of pulmonary Pancreatitis
neoplasms
Pancreatic pseudocyst
Hemothorax
Meigs' syndrome
Chylothorax
Chylous ascites
Malignancy-related
Carcinoma Malignant ascites
Lymphoma Subphrenic abscess
Mesothelioma Hepatic abscess (bacterial, amebic)
Leukemia Splenic abscess, infarction
Chylothorax Miscellaneous
Paraproteinemia (multiple myeloma, Endometriosis
Waldenstrom's macroglobulinemia)
Drowning
Paramalignant effusions
Electrical burns
Other inflammatory disorders Capillary leak syndromes
Pancreatitis (acute, chronic) Extramedullary hematopoiesis
Benign asbestos pleural effusion
Pulmonary embolism
Radiation therapy
Uremic pleurisy
Sarcoidosis
Postcardiac injury syndrome
Acute respiratory distress syndrome

(ARDS)
Immunoglobulin G4-related disease

(fibroinflammatory)
Contributor Disclosures
Charlie Strange, MD Employment: AlphaNet [Alpha-1]; PulManage [COPD]. Grant/Research/Clinical
Trial Support: Adverum [Alpha-1]; Arrowhead [Alpha-1]; AstraZeneca [COPD]; CSL Behring [Alpha-1];
Grifols [Alpha-1]; Novartis [LAM]; Nuvaira [COPD]; Pandorum [ARDS]; Takeda [Alpha-1]; Vertex [Alpha-1].
Consultant/Advisory Boards: CSL Behring [Alpha-1]; Takeda [Alpha-1]; Vertex [Alpha-1]. Other Financial
Interest: Uptake Medical [COPD]. All of the relevant financial relationships listed have been mitigated. V
Courtney Broaddus, MD No relevant financial relationship(s) with ineligible companies to
disclose. Julio A Ramirez, MD, FACP Grant/Research/Clinical Trial Support: Eli Lilly [Monoclonal
antibodies]; Janssen [Vaccines]; Pfizer [Vaccines]. Consultant/Advisory Boards: Dompe [Infectious
diseases]; Nabriva [Respiratory infections]; Paratek [Respiratory infections]; Pfizer [Vaccines]. All of the
relevant financial relationships listed have been mitigated. Geraldine Finlay, MD No relevant financial
relationship(s) with ineligible companies to disclose. Sheila Bond, MD No relevant financial
relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Epidemiology, Clinical Presentation, and Diagnostic Evaluation of Parapneumonic Effusion and Empyema in Adults - UpToDate

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Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults - UpToDate 25/10/22 16:31

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Epidemiology, clinical presentation, and diagnostic

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

setting of an adjacent pneumonia ( table 1).

● An uncomplicated or simple parapneumonic effusion refers to a free-flowing

● A complicated parapneumonic effusion refers to an effusion that has been infected

● A complex effusion refers to an effusion with internal loculations.

● A uniloculated effusion is one that is without internal septae (free-flowing or fixed).

Incidence — Parapneumonic effusions and empyema are relatively common

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

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

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

parapneumonic empyema ( table 3) [15,18]. Parapneumonic pleural space infections

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

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

Staphylococcus aureus accounts for approximately 10 to 15 percent of parapneumonic

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

Mycobacteria — Mycobacterial effusion and empyema are considerably less frequent

Diagnostic imaging — Chest radiography, ultrasonography, and computed tomography

Chest radiography — Most parapneumonic effusions or empyemas are initially

approximately 10 percent of pleural effusions, in most cases due to the coexistence of

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

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

During the fibrinopurulent and organizing stages of complicated parapneumonic

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

● Parietal pleural thickening is seen in 86 percent and pleural enhancement in 96

Thoracentesis and pleural fluid analysis — Most cases of suspected parapneumonic

Fluid obtained by thoracentesis should be sent for the following:

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

● Microbiologic analysis – Microbiologic analysis of the pleural fluid with appropriate

Blood and pleural culture results yield a diagnosis in approximately 60 percent of

for the remaining 40 percent:

• Anaerobic organisms may be difficult to culture

Some centers have begun routine molecular analysis of parapneumonic effusions to

Special stains and cultures should be requested when unusual organisms or

● Cytology – Cytologic examination for appropriate stains (eg, mycobacteria,

for cytology for malignant cells is prudent.

Novel biomarkers of infection (eg, C-reactive protein, procalcitonin, STREM-1) in pleural

Procalcitonin's usefulness for distinguishing bacterial from nonbacterial parapneumonic

Several conditions need to be entertained when evaluating a suspected parapneumonic

● Pleural fluid exudates – The differential diagnosis of an exudative pleural effusion is

● Pleural effusion or masses on imaging – Distinguishing loculated pleural fluid from a

In most patients, the diagnosis of a parapneumonic effusion and empyema is made by a

Uncomplicated parapneumonic effusion — A parapneumonic effusion is considered

● The pleural effusion is free-flowing and too small to sample.

In most cases, uncomplicated parapneumonic effusions resolve with appropriate

Complicated parapneumonic effusion and empyema — A parapneumonic effusion is

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

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

SUMMARY AND RECOMMENDATIONS

● Definition and epidemiology – A parapneumonic effusion is a pleural effusion that

● Pathogenesis – Parapneumonic effusion and empyema may be part of a

• Stage 2 is a fibrinopurulent stage where infection precipitates organization and

• Stage 3 is characterized by a thickened fibrinous coating that may limit lung

● Microbiology – The microbiology of complicated pleural effusions and empyema

• Parapneumonic – Parapneumonic pleural space infections typically result as

• Non-parapneumonic – The list of pathogens associated with non-

● Suspecting parapneumonic effusion – Among patients with pneumonia, the

● Thoracentesis – Most cases of suspected parapneumonic effusion or empyema

• In some cases, therapeutic thoracentesis is simultaneously performed when

● Differential diagnosis – Several conditions need to be entertained when evaluating

¶ Exudative uncomplicated parapneumonic effusions are generally neutrophilic and have an

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