Diagnostic approach to community-acquired pneumonia in adults

Author
John G Bartlett, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Anna R Thorner, MD
Contributor disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Aug 2016. | This topic last updated: Jul 19, 2016.
INTRODUCTION Community-acquired pneumonia (CAP) is defined as an acute infection of the
pulmonary parenchyma in a patient who has acquired the infection in the community, as
distinguished from hospital-acquired (nosocomial) pneumonia. A third category of pneumonia,
designated healthcare-associated pneumonia, is acquired in other healthcare facilities such as
nursing homes, dialysis centers, and outpatient clinics or within 90 days of discharge from an acute
or chronic care facility. The rationale for the separate designation of HCAP was that patients with
HCAP were at higher risk for multidrug-resistant (MDR) organisms. However, several studies have
shown that many patients defined as having HCAP are not at high risk for MDR pathogens [1-3].
Furthermore, although interaction with the healthcare system is potentially a risk for MDR
pathogens, underlying patient characteristics are also important independent determinants of risk
for MDR pathogens. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospitalacquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on
'Pneumonia types'.)
CAP is a common and potentially serious illness [4-6]. It is associated with considerable morbidity
and mortality, particularly in older adult patients and those with significant comorbidities.
(See "Prognosis of community-acquired pneumonia in adults".)
The diagnostic approach to CAP in immunocompetent adults will be reviewed here. A variety of
other important issues related to CAP are discussed separately. These include:
The epidemiology and microbiology of CAP (see "Epidemiology, pathogenesis, and
microbiology of community-acquired pneumonia in adults")
The use of sputum cultures for the evaluation of bacterial pneumonia (see "Sputum cultures
for the evaluation of bacterial pneumonia")
The approach to patients with nonresolving pneumonia (see "Nonresolving pneumonia")
Treatment recommendations for CAP in patients treated in the outpatient setting
(see "Treatment of community-acquired pneumonia in adults in the outpatient setting")
Treatment recommendations for CAP in patients requiring hospitalization (see "Treatment of
community-acquired pneumonia in adults who require hospitalization")
The evidence for efficacy of different antibiotic medications in the empiric treatment of CAP
and issues related to drug resistance (see "Antibiotic studies for the treatment of communityacquired pneumonia in adults")
Pneumonia in special populations, such as aspiration pneumonia and immunocompromised
patients (see "Aspiration pneumonia in adults" and "Pulmonary infections in
immunocompromised patients")

CLINICAL EVALUATION The approach to the patient with community-acquired pneumonia

(CAP) begins with the clinical evaluation followed by chest radiograph with or without microbiologic
testing [7]. A systematic review highlighted the lack of sensitivity of the clinical criteria for an
accurate diagnosis of CAP; even a combination of symptoms (cough) and signs (fever, tachycardia,
and crackles) did not have a sensitivity above 50 percent when using chest radiograph as the
standard [8].
Common clinical features of CAP include cough, fever, pleuritic chest pain, dyspnea, and sputum
production. Mucopurulent sputum production is most frequently found in association with bacterial
pneumonia, while scant or watery sputum production is more suggestive of an atypical pathogen.
Although there are classic descriptions of certain types of sputum production and particular
pathogens (eg, pneumococcal pneumonia and rust-colored sputum), these clinical descriptions do
not help in clinical decision-making regarding treatment because they are rarely seen.
Other common features are gastrointestinal symptoms (nausea, vomiting, diarrhea), and mental
status changes. Chest pain occurs in 30 percent of cases, chills in 40 to 50 percent, and rigors in 15
percent. Because of the rapid onset of symptoms, most individuals seek medical care within the first
few days [9].
On physical examination, approximately 80 percent are febrile, although this finding is frequently
absent in older patients and temperature may be deceptively low in the morning. A respiratory rate
above 24 breaths/minute is noted in 45 to 70 percent of patients and may be the most sensitive sign
in older adult patients; tachycardia is also common. Chest examination reveals audible crackles in
most patients, while approximately one-third have evidence of consolidation. However, no clear
constellation of symptoms and signs has been found to accurately predict whether or not the patient
has pneumonia [10].
The major blood test abnormality is leukocytosis (typically between 15,000 and 30,000 per mm 3)
with a leftward shift. Leukopenia can occur and generally connotes a poor prognosis.
RADIOLOGIC EVALUATION The presence of an infiltrate on plain chest radiograph is
considered the gold standard for diagnosing pneumonia when clinical and microbiologic features
are supportive. A chest radiograph should be obtained in patients with suspected pneumonia when
possible; a demonstrable infiltrate by chest radiograph or other imaging technique is required for the
diagnosis of pneumonia, according to the 2007 consensus guidelines from the Infectious Diseases
Society of America and the American Thoracic Society (IDSA/ATS) [4]. Recommendations are less
clear in the patient with what appears to be a viral infection with nasal congestion and cough; one
approach in these cases is to obtain a chest radiograph when there is an abnormal vital sign with
particular emphasis on a respiratory rate >20 breaths/minute or a fever. This recommendation is
relatively insensitive in older adult patients.
The radiographic appearance of community-acquired pneumonia (CAP) may include lobar
consolidation (image 1 and image 2), interstitial infiltrates (image 3 and image 4 and image
5),and/or cavitation (image 6). It has been taught that lobar consolidation is due to the "typical"
bacteria, and interstitial infiltrates are due to Pneumocystis jirovecii (formerly P. carinii) and viruses.
However, radiologists cannot reliably differentiate bacterial from nonbacterial pneumonia on the
basis of the radiographic appearance [9,11]. There is also substantial interobserver variation in the
interpretation of chest radiographs in patients with possible pneumonia between different

radiologists [12,13] and between emergency room physicians and radiologists [14]. It is also clear
that high-resolution computed tomography (CT) is superior to chest radiography in detecting lesions
and defining anatomical changes [15-17]. Nevertheless, chest radiograph (posteroanterior and
lateral) is generally adequate for clinical care of most patients with CAP.
If the clinical evaluation does not support pneumonia in a patient with an abnormal chest
radiograph, other causes for the radiographic abnormalities must be considered, such as
malignancy, hemorrhage, pulmonary edema, pulmonary embolism, and inflammation secondary to
noninfectious causes. On the other hand, if the clinical syndrome favors pneumonia but the
radiograph is negative, the radiograph may represent a false-negative result. In some cases, this
can be clarified with a CT scan, which, as noted above, has higher sensitivity and accuracy than
chest radiographs for detecting CAP [15].
There are case reports and animal experiments favoring the hypothesis that volume depletion may
produce an initially negative radiograph, which "blossoms" into infiltrates following rehydration [18].
In support of this hypothesis, one population-based cohort study of suspected CAP found that 7
percent of patients with negative initial radiographs developed changes consistent with CAP on
repeat chest radiograph [19].
For hospitalized patients with suspected pneumonia and a negative chest radiograph, the
2007 IDSA/ATS consensus guidelines consider it reasonable to initiate empiric presumptive
antibiotic therapy and repeat the chest radiograph in 24 to 48 hours [4]. The basis for this
recommendation is from the classic studies of pneumococcal pneumonia, which found that the
absence of infiltrate at 24 hours after onset of symptoms indicated the diagnosis needed to be
questioned [20]. Alternatively, a CT scan could be performed in patients with a negative chest
radiograph when there is a high clinical suspicion for pneumonia. CT scan, especially highresolution CT (HRCT), is more sensitive than plain films for the evaluation of interstitial disease,
bilateral disease, cavitation, empyema, and hilar adenopathy [15,21].
CT scanning is not generally recommended for routine use because the data for its use in CAP are
limited, the cost is high, and there is no evidence that it improves outcome. Thus, a chest
radiograph is the preferred method for initial imaging, with CT scan or magnetic resonance imaging
(MRI) reserved for further anatomical definition (eg, detecting cavitation, adenopathy, or mass
lesions).
DIAGNOSTIC TESTING FOR MICROBIAL ETIOLOGY There is agreement that treatment is
best when it is pathogen directed [4-7], but there is little consensus on the practicality of achieving
this goal due to controversies in the value of diagnostic tests.
The 2007 Infectious Diseases Society of America/American Thoracic
Society (IDSA/ATS) consensus guidelines recommend diagnostic testing for a specific organism
when, based on clinical or epidemiologic data, pathogens that would not respond to usual empiric
antibiotic regimens are suspected [4] (see 'Critical microbes' below). These guidelines otherwise
support the following testing strategy, based on patient characteristics and severity of illness:
For outpatients with community-acquired pneumonia (CAP), routine diagnostic tests are
optional.
Hospitalized patients with specific indications should have blood cultures and sputum Gram
stain and culture and/or other tests as outlined in the following Table (table 1); some experts

consider diagnostic tests to be optional for hospitalized patients without severe CAP.
(See 'Hospitalized patients' below.)
Patients with severe CAP requiring intensive care unit (ICU) admission should have blood
cultures, Legionella and pneumococcus urinary antigen tests, and sputum culture (either
expectorated or endotracheal aspirate).
Newer tests that have been approved by the US Food and Drug Administration (FDA) include
polymerase chain reaction (PCR) for detecting Chlamydia pneumoniae and Mycoplasma
pneumoniae as well as 14 respiratory tract viruses. These tests are rapid (one to two hours),
sensitive, and specific. (See 'Chlamydia pneumoniae' below and 'Mycoplasma
pneumoniae'below.)
A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases was
published in 2013 by the IDSA and the American Society for Microbiology [7]. This guide includes
tables summarizing available tests for the diagnosis of CAP; it can be found at the IDSA website.
Critical microbes Some microbes are critical to detect because they represent important
epidemiologic challenges and/or serious conditions that require treatment different from standard
empiric regimens. These organisms include:
Legionella species
Influenza A and B, including avian influenza A H5N1 and avian influenza A H7N9
(see "Clinical manifestations and diagnosis of avian influenza", section on
'Diagnosis' and "Avian influenza A H7N9: Epidemiology, clinical manifestations, and
diagnosis", section on 'Diagnosis')
Middle East respiratory syndrome coronavirus (MERS-CoV)
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
Agents of bioterrorism
Other emerging pathogens
Outpatients Testing for a microbial diagnosis is usually not performed in outpatients because
empiric treatment is almost always successful. In one study of over 700 ambulatory patients treated
for CAP, empiric antibiotics (a macrolide or fluoroquinolone in >95 percent) were almost universally
effective; only 1 percent required hospitalization due to failure of the outpatient regimen [22].
The 2007 IDSA/ATS consensus guidelines suggest that routine tests to identify an etiology for CAP
are optional for patients who do not require hospitalization [4]. An exception is in clinical or
epidemiologic settings suggesting a critical microbe is the etiologic agent, in which tests for a
microbial diagnosis are important. (See 'Critical microbes' above and "Sputum cultures for the
evaluation of bacterial pneumonia", section on 'Community-acquired pneumonia'.)
Hospitalized patients Most hospitalized patients with CAP in the United States are treated
empirically with no etiologic diagnosis. A review of the experience of Medicare for 17,340 patients
hospitalized for CAP in 2009 showed a microbial diagnosis was made in only 7.6 percent of cases
[23]. Several reasons for this include the distancing of the laboratory from the site of care; the
Clinical Laboratory Improvement Amendments (CLIA), a ruling that rid hospitals of housestaff labs
in 1988; a perception that the quality of microbiology as applied to sputum Gram stain and culture
was variable but generally poor; the Medicare Performance Indicator policy that required
administration of antibiotics within six hours of registration in emergency rooms (a requirement that

has been discontinued); and a randomized trial showing that medical care outcomes were as good
with empiric decisions based on guidelines as they were with pathogen-directed antibiotics [24].
Despite these observations and realities, there is interest in increasing diagnostic microbiologic
studies in CAP patients along with increased emphasis on better quality in the traditional tests and
use of newer molecular techniques [25]. The emphasis on pathogen-directed treatment is motivated
by a desire to reduce unnecessary complications (including Clostridium difficile infection [26]), to
limit antibiotic overuse, to reduce resistance, and to improve care [25].
A prospective study published in 2005 evaluated the diagnostic yield of traditional microbiologic
tests in 262 hospitalized patients with CAP [27]. Clinical samples included sputum for Gram
staining, culture, and detection of pneumococcal antigen; blood for culture and serologic tests; urine
for Legionella and pneumococcal antigens; and specimens obtained by bronchoscopy. The
following findings were noted:
A pathogen was identified in 158 (60 percent) patients, with Streptococcus
pneumoniae identified most commonly, accounting for 97 of 158 (61 percent) identified
pathogens.
Adequate sputum samples were obtained in only 44 patients (17 percent); Gram stain was
diagnostic and confirmed by a positive sputum culture in 36 of the 44 patients (82 percent).
Urinary pneumococcal antigen test was positive in 52 of the 97 (54 percent) patients with
pneumococcal pneumonia.
Blood cultures were positive in 40 of 254 (16 percent) patients.
Bronchoscopy provided additive diagnostic value in 18 of 37 patients (49 percent) who did
not expectorate sputum and in 14 of 27 patients (52 percent) who failed treatment within 72
hours after admission.
There is substantial interest and progress in the development of molecular methods to detect
multiple pathogens [28,29]. Potential advantages are speed and enhanced sensitivity and
specificity. This technology is now available for detecting 16 viral pathogens, Mycoplasma
pneumoniae, C. pneumoniae, and Legionella pneumophila [28,29]. In a prospective study of 184
adults with CAP, investigators used a comprehensive battery of tests using blood cultures, urinary
antigen tests, and respiratory tract specimens for conventional culture plus PCR for respiratory
viruses and atypical agents (figure 1) [30]. For S. pneumoniae and Haemophilus influenzae, they
used quantitative PCR to avoid the detection of colonizing flora. A likely pathogen was detected in
78 percent of cases and in 89 percent among patients with complete sampling. S. pneumoniae was
the most common pathogen (38 percent), and PCR provided the highest yield for its detection.
Respiratory viruses were found in 29 percent of cases, and many had bacterial superinfection.
Blood cultures Pretreatment blood cultures are positive for a pathogen in 7 to 16 percent of
hospitalized patients [27,31-33]. S. pneumoniae accounts for two-thirds of the positive blood
cultures.
Blood cultures are commonly advocated in hospitalized patients with CAP because [34]:
When positive for a likely pathogen, the microbial diagnosis is established.
This is the only diagnostic test done, in most cases, and is the major source of microbiologic
data for CAP for many hospitals.

The isolates identified serve as an important resource for tracking resistance patterns of S.
pneumoniae (eg, the United States Centers for Disease Control and Prevention [CDC]
surveillance network is highly dependent on blood culture data [35]). These are the data used
for evaluating efficacy of current S. pneumoniae vaccines and the serotypes needed for
inclusion in future vaccines [36-38]. (See "Impact of universal infant immunization with
pneumococcal (Streptococcus pneumoniae) conjugate vaccines in the United States", section
on 'Invasive disease caused by nonvaccine serotypes'.)
Counter arguments for not obtaining these tests are that [39-41]:
The blood culture positivity rate is relatively low.
There is a high rate of false-positive blood cultures (10 percent in one study [40]).
Contaminants may actually prolong hospital stays due to a perceived need for vancomycin to
treat S. aureus, when the laboratory calls to report gram-positive cocci, which are actually
coagulase-negative staphylococci that are not yet identified.
Positive cultures rarely lead to modification or narrowing of antibiotic therapy [32].
In one study, variables associated with bacteremia included absence of prior antibiotic use, chronic
liver disease, pleuritic pain, tachycardia (>125 beats per minute), tachypnea (>30 breaths per
minute), and systolic hypotension (<90 mmHg) [33].
Some studies have suggested that sicker patients (as judged by the pneumonia severity index
[PSI]) are more likely to have positive blood cultures [31], although this has not been observed in
other reports [27]. The 2007 IDSA/ATS consensus guidelines recommend blood cultures for
hospitalized patients with specific indications, including all patients who require admission to the
ICU for CAP, and consider them optional for other patients (table 1).
Sputum Expectorated sputum can be submitted for Gram stain and culture, but the utility of
these tests is subject to substantial controversy due in part to variations in the quality of service and
distance of the clinical microbiology laboratory, the apparent success of empiric treatment, and the
need to initiate antibiotic treatment while in the emergency room or clinic. Thus, the rate of
pathogen detection varies in studies, some with a pathogen detection rate of <10 percent [42,43]
and others with yields of 54 to 86 percent, particularly in patients with bacteremic pneumococcal
pneumonia or when invasive procedures were used to obtain samples [34,44,45]. A review of
Medicare data from 33,000 patients hospitalized for CAP in the United States showed that only 7.6
percent had a pathogen detected [23].
The 2007 IDSA/ATS consensus guidelines recognize the limitations of sputum Gram stain and
culture [4]. The guidelines recommend that pretreatment sputum Gram stain and culture of
expectorated sputum be performed only if a good quality sputum can be obtained, with appropriate
measures in place for collection, transport, and processing to assure quality performance. Under
these circumstances, expectorated sputum specimens are recommended for hospitalized patients
with any of the following criteria:
Intensive care unit admission
Failure of antibiotic therapy (either outpatients or hospitalized patients), although the clinician
must be aware that posttreatment specimens are notorious for colonization by resistant
bacteria

Cavitary lesions, although anaerobic bacteria, the usual cause of primary lung abscess,
would require an uncontaminated sputum sample for detection; this requires culture of
empyema fluid, a transtracheal aspirate, transthoracic aspirate or (possibly) a quantitative
bronchoscopic aspirate.
Active alcohol abuse
Severe obstructive or structural lung disease
Immunocompromised host
Pleural effusion
Epidemic pneumonia
Epidemiologic or clinical data suggesting a pathogen likely to be resistant to standard
therapy, such as gram-negative bacilli or methicillin-resistant Staphylococcus aureus
Epidemiologic or clinical data suggesting a pathogen of clinical or epidemiologic interest,
such as Legionella, Middle East respiratory syndrome coronavirus, severe acute respiratory
syndrome coronavirus, avian influenza A H7N9, or agents of bioterrorism
Standards of quality control for sputum culture for bacterial pathogens have been proposed and
include:
The specimen should be a deep cough specimen obtained prior to antibiotics.
Cultures should be performed rapidly after collection, preferably within two hours; the
alternative for rapid plating of the sample is to retain the specimen at 4C if the delay is more
than two hours [46].
A "good" sputum sample is one with polymorphonuclear leukocytes (PMNs) but few (or no)
squamous epithelial cells (SECs) on Gram stain. Several guidelines have been proposed to
evaluate the quality of sputum samples. These guidelines have proposed different
combinations and cutoffs of the minimum number of SECs and/or polymorphonuclear
leukocytes (PMNs) per low power field, but none of these parameters can be considered to be
clearly superior. An example of one approach is to reject all specimens with more than
10 SECs/LPF(picture 1), without considering the number of PMNs. It should be noted that
these criteria do not apply to cultures for Legionella or mycobacteria [47]. (See "Sputum
cultures for the evaluation of bacterial pneumonia", section on 'Expectorated sputum'.)
The sensitivity and specificity of the sputum Gram stain vary substantially in different settings. A
meta-analysis evaluated 12 studies of the sensitivity and specificity of the sputum Gram stain in
CAP [48]. The sensitivity of Gram stain compared with culture ranged from 15 to 100 percent and
specificity ranged from 11 to 100 percent.
Culture results should be interpreted based upon the following findings:
Quantitation of growth (heavy, moderate, or light)
Clinical correlation
Correlation with the Gram stain
True pathogens should be present in moderate or heavy amounts by Gram stain and culture.
However, some agents are regarded as significant regardless of concentration,
includingLegionella spp, Bacillus anthracis, Mycobacterium tuberculosis, Mycoplasma

pneumoniae, C. pneumoniae, and Chlamydia psittaci; these respiratory pathogens are virtually
never colonizers but always represent disease.
Antibiotics may alter the yield of any subsequent culture of respiratory secretions. Specimens
collected after antibiotics are given are more likely to grow S. aureus or gram-negative bacilli
(GNB), which usually represent early airway contaminants.
When S. pneumoniae and H. influenzae are the etiologic agent, false-negative cultures are common
because of their fastidious growth requirements and the lack of selective media. By contrast, S.
aureus and GNB are relatively rare pulmonary pathogens that are easily grown in respiratory
secretions because they are hardy and easily recognized by growth on selective media. The failure
to grow these organisms is strong evidence against their presence and, when grown, they often
represent contaminants.
The preferred tests for Legionella are culture on selective media and the urinary antigen assay. A
travel history should be obtained in patients presenting with CAP and Legionella testing ordered for
patients who have traveled in the two weeks before symptom onset [4]. The risk
of Legionella infection is especially associated with contaminated water in hotels, although
outbreaks have occurred in diverse settings including hospitals, cruise ships, and industrial plants.
(See 'Urinary antigen' below and "Clinical manifestations and diagnosis of Legionella infection",
section on 'Specific laboratory diagnosis' and "Epidemiology and pathogenesis of Legionella
infection".)
Urinary antigen Alternative or complementary methods to detect S.
pneumoniae and Legionella are urinary antigen assays. There are several advantages and
disadvantages to urine antigen testing compared with culture.
The advantages are:
Most studies show these urinary antigen tests are more sensitive and specific than Gram
stain and culture of sputum as commonly done by most labs.
Urine specimens are usually available in the 30 to 40 percent of patients who cannot supply
expectorated sputum.
Results of urine antigen testing are immediately available.
The test retains validity even after the initiation of antibiotic therapy.
The test has high sensitivity compared with blood cultures and sputum studies and high
specificity.
The urinary antigen tests for Legionella and S. pneumoniae are FDA cleared and provide
results in minutes; the reagents are commercially available, and they require no equipment.
They are not Clinical Laboratory Improvements Amendments (CLIA) waived, meaning they
must be done by a laboratory technician.
Disadvantages of the urine antigen assay for the diagnosis of pneumococcus include:
The sensitivity and specificity may be less in patients without bacteremia.
There is no microbial pathogen available for antibiotic sensitivity testing.
These tests require a licensed technician and cannot be done by the provider despite their
simplicity.

A disadvantage of the urine antigen assay for the diagnosis of Legionella is that it is only useful for
the diagnosis of L. pneumophila group 1 infection. Nevertheless, this serogroup accounts for 80
percent of Legionnaires' disease acquired in the community and in hotels [49,50].
Nosocomial Legionella infections often involve other serotypes, so sensitivity is decreased.
A prospective trial evaluated the sensitivity and specificity of the pneumococcal urinary antigen test
in 107 patients with bacteremic pneumococcal infection compared with 106 patients with septicemia
caused by other organisms [51]. Antigen was detected in 88 of 107 pneumococcal bacteremic
patients (82 percent) compared with 3 of 106 patients with bacteremia due to other pathogens (3
percent), for a sensitivity and specificity of 82 and 97 percent, respectively. It is important to note
that these findings were in patients with bacteremic pneumococcal pneumonia and may not reflect
what occurs in patients without bacteremia.
In a subsequent prospective study that included 171 adults hospitalized with CAP caused by S.
pneumoniae, the majority of whom did not have S. pneumoniae isolated from blood cultures, the
sensitivity of the pneumococcal urinary antigen was 71 percent and the specificity was 96 percent
[52]. Among patients with a definite diagnosis of pneumococcal CAP, the sensitivity of urinary
antigen testing was 78 percent compared with 57 percent in those with a probable diagnosis. A
definite diagnosis was defined as S. pneumoniae isolated from a blood culture or pleural fluid
culture or detected by PCR from pleural fluid, whereas a probable diagnosis required S.
pneumoniae to be the predominant organism in a good quality sputum sample with an
accompanying positive Gram stain. Pneumococcal CAP was diagnosed exclusively by the urinary
antigen test in 75 cases (44 percent). The results of the urinary antigen test led clinicians to reduce
the spectrum of antibiotics in 41 of 474 patients with CAP (9 percent). This study suggests that,
although the sensitivity of the pneumococcal urinary antigen test is lower in patients who are not
bacteremic, the presence of a positive urinary antigen test in a nonbacteremic patient can be helpful
for tailoring therapy.
According to the 2007 IDSA/ATS consensus guidelines on CAP, the pneumococcal urinary antigen
assay may augment the standard diagnostic methods of blood culture and sputum Gram stain and
culture, with the potential advantage of rapid results similar to those for sputum Gram stain [4]. It is
of particular value when antibiotic therapy has already been initiated, prior to obtaining a sputum
sample; specimens may remain positive three days after antibiotic initiation. A disadvantage
compared with culture is the inability to test antibiotic sensitivity. (See"Pneumococcal pneumonia in
adults".)
The standard tests to diagnose Legionella spp infection in most clinical laboratories are culture on
selective media and the urinary antigen assay (table 2) [49,53,54]. (See "Clinical manifestations and
diagnosis of Legionella infection".)
Polymerase chain reaction Like the urinary antigen assay, PCR improves the accuracy of the
microbiologic diagnosis for patients with CAP with a rapid turnaround time [30,55,56]. One limitation
of PCR when used on respiratory specimens, including bronchoscopic samples, is that specimens
are contaminated by the upper airway flora [57,58]. Thus, a quantitative or semiquantitative PCR
assay is necessary, and the results must be interpreted with the understanding that some of the
pathogens isolated may be colonizers of the upper respiratory tract [30]. Another limitation is that
these are not point-of-care tests, meaning they require a laboratory and laboratory technician. This

may present logistical problems in facilities that have outsourced microbiology or have limited
coverage
Viral infections Viral pathogens that cause community-acquired pneumonia include influenza,
adenovirus, parainfluenza, respiratory syncytial virus, and human metapneumovirus. The diagnosis
of these viruses can be made by culture, serology, or through rapid diagnostic testing with enzyme
immunoassay (EIA), immunofluorescence, or PCR. PCR-based diagnostic panels have been
developed that can detect multiple respiratory viruses simultaneously and can be performed in two
to three hours in hospital laboratories [59-63]. Using such a panel can aid in the rapid diagnosis of
viral pneumonia, which might reduce the unnecessary use of antibacterial agents. Caution is
necessary in interpretation since up to 15 percent of healthy persons harbor a respiratory tract virus
at any point of time [64]. An exception is influenza since detection of this virus usually indicates
infection. (See 'Polymerase chain reaction' above and"Parainfluenza viruses in
adults" and "Respiratory syncytial virus infection: Clinical features and diagnosis" and "Human
metapneumovirus infections" and "Diagnosis of seasonal influenza in adults" and "Diagnosis,
treatment, and prevention of adenovirus infection", section on 'Pneumonia' and "Clinical
manifestations of seasonal influenza in adults", section on 'Duration of shedding'.)
The diagnosis of influenza infection is discussed below. (See 'Influenza' below.)
Nonresolving pneumonia The diagnostic approach to patients with nonresolving pneumonia is
presented separately. (See "Nonresolving pneumonia".)
PROCALCITONIN AND CRP Biologic markers are sometimes used to try to distinguish between
bacterial and nonbacterial causes of pneumonia [65]. The two most promising are procalcitonin
(PCT) and C-reactive protein (CRP).
Procalcitonin is a peptide precursor of calcitonin that is released by parenchymal cells in response
to bacterial toxins, leading to elevated serum levels in patients with bacterial infections; in contrast,
procalcitonin is down-regulated in patients with viral infections. Procalcitonin is measured by two
commercially available tests, the Kryptor assay and the LUMI assay; the former is preferred due to
higher sensitivity [66].
Procalcitonin has been studied prospectively to facilitate the decision of whether to use antibacterial
agents in patients with pneumonia and when antibiotics can be safely stopped. In two trials,
clinicians were strongly recommended not to prescribe antibacterials in patients with a procalcitonin
level <0.1 mcg/L but were encouraged to use antibacterials in patients with levels
>0.25 mcg/L [67,68]. The analysis suggested the correct decision in 83 percent [68]. Several trials
have shown that using procalcitonin results to help determine whether antibiotics are necessary
results in lower rates of antibiotic exposure [67-69].
In a Cochrane meta-analysis that used individual patient data from 14 trials of 4221 patients with
acute respiratory infections (half of whom had community-acquired pneumonia [CAP]), procalcitonin
guidance for antibiotic use was associated with a reduction in antibiotic exposure (from a median of
eight days to four days) without an increase in mortality or treatment failure in any clinical setting
(eg, outpatient clinic, emergency department) or in patients with any type of acute respiratory
infection, including CAP [70]. Most patients with a diagnosis of CAP supported by imaging showing
a pulmonary infiltrate will be treated with an antibiotic, but a low procalcitonin may support the
impression of a viral or other nonbacterial cause. The procalcitonin may also facilitate the decision

to stop antibiotics since the levels reflect bacterial replication. We consider procalcitonin a useful
adjunct to the antibiotic decisions in CAP, but other observations and clinical judgment are also
important.
Other studies have shown that procalcitonin levels correlate with the severity of pneumonia [71,72].
In one small study, procalcitonin levels increased over time in non-survivors but decreased in
survivors [72]. Procalcitonin levels also predict bacteremia [73]. These studies show that
procalcitonin levels help to distinguish between bacterial and viral pneumonia, reduce antibacterial
use, predict severity based on the magnitude of the result, and may predict survival.
The use of procalcitonin for distinguishing between bacterial and viral bronchitis is discussed in
detail separately. (See "Acute bronchitis in adults", section on 'Procalcitonin'.)
CRP has shown more limited utility, due in part to the paucity of studies. One study showed a CRP
>40 mg/L had a sensitivity and specificity for bacterial pneumonia of 70 and 90 percent, respectively
[74]. Another study that included 364 patients with respiratory infection showed a sensitivity of 73
percent and specificity of 65 percent [75]. Another report indicated particularly high CRP levels in
patients with pneumococcal pneumonia (mean 178 mg/L) [76]. CRP appears to be less sensitive
than procalcitonin for the detection of bacterial pneumonia [72]. Both of these tests need to be
interpreted in the context of clinical observations.
ORGANISMS OF SPECIAL INTEREST The most common etiologic agents of communityacquired pneumonia (CAP) or those that are less common but require more specific therapy are
discussed below. The microbial etiology of CAP in studies from different countries is reviewed in the
Table (table 3) and is discussed in greater detail separately. (See "Epidemiology, pathogenesis, and
microbiology of community-acquired pneumonia in adults".)
Streptococcus pneumoniae S. pneumoniae historically has accounted for about 65 percent of
bacteremic pneumonia cases [77], and it continues to be the most common identified pathogen in
nearly all studies. (See "Epidemiology, pathogenesis, and microbiology of community-acquired
pneumonia in adults", section on 'S. pneumoniae'.)
Nevertheless, clinical studies from the United States show infrequent detection of any pathogen in
the majority of CAP cases [23,78], and the yield of S. pneumoniae is <20 percent of all cases of
CAP even with assiduous attempts to detect a pathogen [78,79]. One of the highest yields of S.
pneumoniae in recent years was from a study from Sweden that used semiquantitative polymerase
chain reaction (PCR); 70 of 184 cases of CAP among inpatients (38 percent) were found to be
caused by S. pneumoniae (figure 1) [30]. Note that care must be exercised in cross-country
comparisons of the rate of detection of S. pneumoniae due to differences in pneumococcal vaccine
strategies as well as diagnostic methods.
The yield with sputum Gram stain and culture is variable and dependent on the quality of the
sputum processing, the experience of the reader, and population studied. Among patients with
bacteremic pneumococcal pneumonia, the yield with expectorated sputum ranges from 50 [80] to
80 percent [34] in labs with good quality control. Diagnostic ability may be enhanced with the
addition of a urine antigen test to sputum culture. (See 'Urinary antigen' above.)
It is expected that a PCR assay for the detection of S. pneumoniae from respiratory specimens will
be available in the near future, but this will probably require quantitation when using specimens

contaminated by the oral flora due to the sensitivity of these methods and the frequency of carriage
of pneumococci in the upper airways [81].
The pneumococcal urinary antigen assay is discussed above. (See 'Urinary antigen' above.)
Staphylococcus aureus S. aureus is an infrequent pulmonary pathogen, but it is important to
detect since it is associated with severe disease and is usually resistant to standard antibiotics for
CAP. Prior studies emphasized the importance of methicillin-resistant strains (MRSA) that are most
common in association with influenza [82-85]. S. aureus continues to be an uncommon, but often
highly lethal, cause of CAP in patients with influenza [86].
S. aureus should be suspected in patients with influenza and a bacterial superinfection, especially
those with the clinical characteristics of staphylococcal toxic shock syndrome. S. aureusshould also
be suspected in a previously healthy young adult or child with a rapidly progressive lung infection
that is often accompanied by pulmonary necrosis, shock, and neutropenia; these features have
been associated with the USA 300 strain of S. aureus that causes community-acquired MRSA
infection. (See "Clinical manifestations of seasonal influenza in adults", section on 'CAMRSA' and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in
adults", section on 'S. aureus' and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults:
Epidemiology", section on 'Community-associated MRSA infection' and "Virulence determinants of
community-acquired methicillin-resistant Staphylococcus aureus".)
Influenza Influenza is important to recognize because of the need for appropriate infection
control in hospitalized patients, for public health reporting purposes, and for rapid treatment with
antiviral agents. During influenza outbreaks, most patients can be diagnosed on clinical grounds
alone. Rapid point-of-care diagnostic tests can be done in an emergency room or office without a
laboratory technician; these tests show a sensitivity of only about 50 to 60 percent, but specificity is
>95 percent, so a negative result does not rule out influenza [87,88]. Real-time reversetranscriptase PCR is the test of choice to diagnose influenza but requires a laboratory and a
laboratory technician.
The need to know the influenza type depends partly on whether multiple influenza strains with
different resistance patterns are circulating. For example, the majority of seasonal influenza H1N1
during the 2008 to 2009 season were resistant to oseltamivir, but almost all isolates of pandemic
H1N1 influenza in 2009 to 2012 were susceptible to oseltamivir [89,90]. (See"Diagnosis of seasonal
influenza in adults" and "Clinical manifestations and diagnosis of pandemic H1N1 influenza ('swine
influenza')" and "Treatment of seasonal influenza in adults" and"Treatment and prevention of
pandemic H1N1 influenza ('swine influenza')" and "Antiviral drug resistance among seasonal
influenza viruses".)
For severe and sporadic cases of influenza-like illness, there is more urgency to make a specific
diagnosis due to concern for avian influenza A H5N1, avian influenza A H7N9, or other emerging
strains. In such situations, PCR for influenza is appropriate [87]. Reagents to test for novel influenza
strains when they first emerge may be available only in public health laboratories; local hospital
laboratory supervisors will know the specimen referral process. (See "Diagnosis of seasonal
influenza in adults" and "Clinical manifestations and diagnosis of avian influenza", section on
'Diagnosis' and "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis",
section on 'Diagnosis'.)

Viral culture takes approximately two to five days to yield a result, is less sensitive than PCR, and is
mainly used to track which viruses are circulating during a given season [87]. There needs to be
caution in attributing pneumonia to respiratory viruses, since about 15 percent of healthy adults
harbor a virus without symptoms [64]. An exception is influenza, which is rarely detected in the
absence of clinical illness.
Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus
(MERS-CoV) emerged in 2012 to cause severe pneumonia in patients in Saudi Arabia. It has also
caused disease in other countries among individuals who traveled to the Middle East or who were
close contacts of individuals with MERS-CoV infection. Patients with an acute respiratory syndrome
who have an epidemiologic risk factor for MERS-CoV infection should be tested for MERS-CoV
infection using real-time reverse-transcriptase PCR of respiratory specimens and other assays (eg,
serology). The approach to diagnosis of MERS-CoV is discussed in greater detail separately [91].
(See "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis", section
on 'Diagnosis'.)
Legionella spp Legionella is implicated in approximately 2 to 9 percent of CAP cases,
depending on the site of care (severity). (See "Epidemiology, pathogenesis, and microbiology of
community-acquired pneumonia in adults".)
Legionella is important to identify because of the potential to cause epidemics (usually in hospitals
and hotels). Outbreaks usually reflect contaminated water sources. This pathogen is resistant to all
beta-lactams and Legionella spp infection has a relatively high mortality rate, even with proper
treatment. (See "Treatment and prevention of Legionella infection".)
Chlamydia pneumoniae The incidence of C. pneumoniae in adults with CAP has varied in
different studies from 0 to 20 percent [30,92-94], although the validity of these data is in question
due to problems with diagnostic testing [95,96]. One problem is the use of a serologic test in many
studies, which lacks both sensitivity and specificity for C. pneumoniae [95]. In addition, positive
serologic results may represent either current or past infection. Some authorities feel the disease is
rarely diagnosed because its occurrence is largely limited to infrequent outbreaks and some
consider the only valid tests to be tissue culture [95] or PCR [97]. In 2012, a multiplex PCR assay
was cleared by the US Food and Drug Administration (FDA) for the diagnosis of C.
pneumoniae using nasopharyngeal samples [63,98]. (See "Pneumonia caused by Chlamydia
pneumoniae in adults", section on 'Diagnosis'.)
Mycoplasma pneumoniae Mycoplasma pneumoniae has historically been considered a
pathogen primarily of children and adolescents, but there are reports of increasingly high rates of
infection in adults, especially older adults. Diagnostic methods to detect M. pneumoniae infection
include culture (which is rarely available), PCR, and serology with IgM and IgG (the most commonly
performed assay) [99,100]. In 2012, a multiplex PCR assay was cleared by the FDA for the
diagnosis of M. pneumoniae using nasopharyngeal samples [63,98]. The difficulty of using serology
for diagnosis is the serologic response is often delayed so that results may not be available at the
time of selection of antimicrobial therapy. The other concerns are the difficulty in showing a
correlation between positive results of standard tests and response to therapy in adults [101] and
poor correlation when comparing PCR, serology, and culture [102]. (See "Mycoplasma pneumoniae
infection in adults", section on 'Diagnosis'.)

Anaerobic bacteria Anaerobic bacteria were well-recognized agents of aspiration pneumonia

and lung abscess during the period 1970 to 1980 when transtracheal aspiration was a common
method to obtain uncontaminated specimens that were valid for anaerobic culture [103,104].
Transtracheal aspiration is no longer performed due to safety concerns. Subsequently, there has
been interest in the use of quantitative cultures of bronchoscopic aspirates using bronchoalveolar
lavage or the protected brush catheter [105]. Although this procedure can be done, there is only one
published study documenting the validity of this approach, and strict quality assurance is critical
including the admonition to exclude patients who have received antibiotics, avoid lidocaine with
preservative, and expedite processing of cultures due to the fastidious nature of these organisms
[106]. Anaerobes should be suspected on clinical grounds when there is aspiration, a pulmonary
cavity in an aspiration-prone patient, putrid discharge (sputum or empyema fluid), and/or no likely
aerobic pathogen. (See "Aspiration pneumonia in adults".)
Bioterrorism agents Agents that may be used for bioterrorism and can cause a pneumonic
syndrome include Bacillus anthracis (inhalational anthrax), Yersinia pestis (pneumonic
plague), Francisella tularensis (tularemia), Coxiella burnetii (Q fever), Legionella spp, influenza
virus, hantavirus, and ricin (table 4) [107]. (See "Identifying and managing casualties of biological
terrorism".)
Emerging infections and zoonoses Several pathogens have emerged from animal sources to
cause outbreaks of respiratory disease in humans (eg, H1N1 pandemic influenza, H5N1 avian
influenza, H7N9 avian influenza, severe acute respiratory syndrome coronavirus, MERS-CoV).
Other zoonotic pathogens that can cause respiratory disease in humans include hantaviruses (eg,
Sin Nombre virus) and Yersinia pestis; such pathogens should be considered in patients with
relevant travel or exposure history [7]. (See 'Influenza' above and 'Middle East respiratory syndrome
coronavirus' above and "Epidemiology of pandemic H1N1 influenza ('swine influenza')" and "Clinical
manifestations and diagnosis of pandemic H1N1 influenza ('swine influenza')" and "Epidemiology,
transmission, and pathogenesis of avian influenza" and "Clinical manifestations and diagnosis of
avian influenza" and "Avian influenza A H7N9: Epidemiology, clinical manifestations, and
diagnosis" and "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory
syndrome coronavirus: Virology, pathogenesis, and epidemiology" and "Epidemiology and
diagnosis of hantavirus infections" and "Clinical manifestations, diagnosis, and treatment of plague
(Yersinia pestis infection)".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The
Basics and Beyond the Basics. The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient education: Pneumonia in adults (The Basics)")

Beyond the Basics topics (see "Patient education: Pneumonia in adults (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Clinical features and radiographic changes are usually not helpful in identifying the etiologic
pathogen of community-acquired pneumonia (CAP). (See 'Clinical evaluation' above
and'Radiologic evaluation' above.)
The presence of an infiltrate on plain chest radiograph is considered the "gold standard" for
diagnosing pneumonia when clinical and microbiologic features are supportive. False-negative
chest radiographs are occasionally attributed to an infection very early in the course (<24
hours), neutropenia, dehydration, and Pneumocystis carinii pneumonia (PCP, but officially
renamed Pneumocystis jirovecii pneumonia). The only common cause of a false-negative
radiograph is infection with PCP. For PCP, spiral computed tomography (CT) scans are more
sensitive. (See 'Radiologic evaluation' above.)
Radiologists cannot reliably differentiate bacterial from nonbacterial pneumonia on the basis
of the radiographic appearance. (See 'Radiologic evaluation' above.)
Tests for a microbial diagnosis in outpatients with suspected CAP are optional. Not testing is
appropriate in most patients since empiric treatment is usually successful.
(See 'Outpatients'above.)
Indications for performing specific tests in hospitalized patients with CAP are shown in the
following Table (table 1). The combination of a good sputum specimen for Gram stain and
culture plus urinary antigen testing is likely to be most useful for the rapid diagnosis of CAP,
although diagnostic testing is optional for patients without specific indications. Patients
hospitalized in the intensive care unit (ICU) should have pretreatment blood cultures, sputum
culture and Gram stain, and urine antigen tests. Multiplex polymerase chain reaction tests are
now available for detection of Chlamydia pneumoniae, Mycoplasma pneumoniae, and 14
respiratory viral pathogens. These are rapid, sensitive, specific, and the preferred tests for
most of these pathogens. (See 'Diagnostic testing for microbial etiology' above.)
The blood culture positivity rate is relatively low but, when positive for a likely pulmonary
pathogen, this establishes the microbial diagnosis. (See 'Blood cultures' above.)
There are some pulmonary pathogens that are particularly important to recognize due to their
epidemiologic significance and/or their need for treatment strategies that differ from the
regimens commonly used by empiric selection. These pathogens include Legionella spp,
community-acquired methicillin-resistant Staphylococcus aureus, influenza, emerging
respiratory viral pathogens such as Middle East respiratory syndrome coronavirus, and agents
of bioterrorism. (See 'Organisms of special interest' above.)