http://emedicine.medscape.com/article/967822-print
eMedicine Specialties > Pediatrics: General Medicine >
Infectious Disease
Pneumonia
Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of
Pediatrics, State University of New York Upstate Medical University
Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology,
Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate
Medical University; Isabel Virella-Lowell, MD, Department of Pediatrics, Division of
Pulmonary Diseases, Pediatric Pulmonology, Allergy and Immunology
Updated: Jan 12, 2009
Introduction
Background
Pneumonia is characterized by inflammation of the alveoli and terminal airspaces in response to
invasion by an infectious agent introduced into the lungs through hematogenous spread or
inhalation. The inflammatory cascade triggers the leakage of plasma and the loss of surfactant,
resulting in air loss and consolidation. This is in contrast to pneumonitis, which is caused by
noninfectious agents such as radiation or chemicals.
An inhaled infectious organism must bypass the host's normal nonimmune and immune defense
mechanisms in order to cause pneumonia. The nonimmune mechanisms include aerodynamic
filtering of inhaled particles based on size, shape, and electrostatic charges; the cough reflex;
mucociliary clearance; and several secreted substances (eg, lysozymes, complement, defensins).
Macrophages, neutrophils, lymphocytes, and eosinophils carry out the immune-mediated host
defense.
Conditions that allow pneumonia-causing infectious organisms to circumvent the upper airway
defense mechanisms include the following:
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Intubation, tracheostomy, impaired cough reflex, and aspiration: These conditions
provide infectious organisms with easier access to the alveoli and terminal airspaces.
Ciliary dyskinesia, bronchial obstruction, viral infection, cigarette smoke, and certain
chemical agents: These conditions create disruption in the mucociliary blanket.
Anatomic abnormalities (eg, sequestrations), gastric fluid aspiration or other causes of
noninfectious inflammation, altered pulmonary blood flow, and pulmonary edema: These
conditions increase the predisposition for pneumonia.
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Immunodeficiency and immunosuppression: These conditions increase predisposition for
pneumonia.
Pathophysiology
Inoculation of the respiratory tract by infectious organisms leads to an acute inflammatory
response in the host that typically lasts 1-2 weeks. This inflammatory response differs according
to the type of infectious agent.
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Viral infections
o These infections are characterized by the accumulation of mononuclear cells in
the submucosa and perivascular space, resulting in partial obstruction of the
airway. Patients with these infections present with wheezing and crackles.
o Disease progresses when the alveolar type II cells lose their structural integrity
and surfactant production is diminished, a hyaline membrane forms, and
pulmonary edema develops.
Bacterial infections
o The alveoli fill with proteinaceous fluid, which triggers a brisk influx of RBCs
and polymorphonuclear cells (red hepatization) followed by the deposition of
fibrin and the degradation of inflammatory cells (gray hepatization).
o During resolution, intra-alveolar debris is ingested and removed by the alveolar
macrophages. This consolidation leads to decreased air entry and dullness to
percussion. Inflammation in the small airways leads to crackles. Wheezing is less
common than in viral infections.
o The inflammation and pulmonary edema that result from these infections cause
the lungs to become stiff and less distensible, thereby decreasing tidal volume.
The patient must increase his or her respiratory rate to maintain adequate
ventilation.
o Poorly ventilated areas of the lung may remain well perfused, resulting in
ventilation/perfusion (V/Q) mismatch and hypoxemia. Tachypnea and hypoxia
are common.
Fungal infections
o Fungal infections are unusual and are typically found in patients with inadequate
immune function (eg, patients with acquired immunodeficiency syndrome
[AIDS], patients who have undergone chemotherapy, newborn infants).
o The pathology may be a diffuse infiltrate of organisms or focal areas of fungal
growth.
o Patients often appear ill and may have more subtle physical findings than their
overall clinical appearance may suggest.
Frequency
United States
Pneumonia accounts for 13% of all infectious illnesses in infants younger than 2 years. In a large
community-based study conducted by Denny and Clyde, the annual incidence rate of pneumonia
was 4 cases per 100 children in the preschool-aged group, 2 cases per 100 children aged 5-9
years, and 1 case per 100 children aged 9-15 years.[1 ]
Mortality/Morbidity
The United Nations Children's Fund (UNICEF) estimates that 3 million children die worldwide
from pneumonia each year. Although most fatalities occur in developing countries, pneumonia
remains a significant cause of morbidity in industrialized nations.
Age
Pneumonia can occur at any age, a lthough it is more common in younger children. Different age
groups tend to be infected by different pathogens, which affects diagnostic and therapeutic
decisions. See Causes for specific details.
Clinical
Physical
Because pneumonia is common and is associated with significant morbidity and mortality,
properly diagnosing pneumonia, correctly recognizing any complications or underlying
conditions, and appropriately treating patients is important.
The signs and symptoms of pneumonia are often nonspecific and widely vary based on the
patient’s age and the infectious organisms involved.
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Newborns
o Newborns with pneumonia rarely cough; they more commonly present with
tachypnea, retractions, grunting, and hypoxemia.
o Grunting in a newborn is due to vocal cord approximation as they try to provide
increased positive end-expiratory pressure (PEEP) and keep their lower airways
open. Grunting suggests a lower respiratory tract disease. Retractions result from
the effort to increase intrathoracic pressure to compensate for decreased
compliance.
Older infants: Grunting may be less common; however, tachypnea, retractions, and
hypoxemia are common and may be accompanied by a persistent cough, congestion,
fever, irritability, and decreased feeding.
Toddlers and preschoolers: These children most often present with fever, cough
(productive or nonproductive), tachypnea, and congestion. They may have some
posttussive emesis.
Older children and adolescents
o This group may also present with fever, cough (productive or nonproductive),
congestion, chest pain, dehydration, and lethargy.
o Extrapulmonary signs and symptoms include (1) abdominal pain or an ileus
accompanied by emesis in patients with lower lobe pneumonia, (2) nuchal rigidity
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in patients with right upper lobe pneumonia, or (3) a rub caused by pericardial
effusion in patients with lower lobe pneumonia due to Haemophilus influenzae
infection.
All children
o Many children present with nasal flaring, which increases airflow to respiratory
surfaces.
o Auscultation of the lung fields may yield rales, wheezing, diminished breath
sounds, tubular breath sounds, or pleural friction rub. The affected lung field may
be dull to percussion. Decreased tactile and vocal fremitus, as well as egophony,
may be appreciated over the area of pneumonia.
Causes
Various organisms cause pneumonia. Bacterial, viral, mycoplasmal, chlamydial, fungal, and
mycobacterial infections are relatively common and have similar presentations, complicating
clinical diagnosis.
To complicate matters, basic laboratory and radiologic testing is often not helpful in determining
the etiology of pneumonia, and the treatments widely vary. However, certain age trends in the
etiology of pneumonia can aid in decision-making, even before testing is complete.
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Newborns (age 0-30 d)
o Infections with group B Streptococcus, Listeria monocytogenes, or gram-negative
rods (eg, Escherichia coli, Klebsiella pneumoniae) are a common cause of
bacterial pneumonia. These pathogens can be acquired in utero, via aspiration of
organisms present in the birth canal, or by postnatal contact with other people or
contaminated equipment.
o Some organisms acquired perinatally may not cause illness until later in infancy,
including Chlamydia pneumoniae, Ureaplasma urealyticum, Mycoplasma
hominis, cytomegalovirus, and Pneumocystis carinii. Infants infected with these
organisms present between age 4-11 weeks with an afebrile pneumonia
characterized by a staccato cough, tachypnea, and, occasionally, hypoxia.
o Community-acquired viral infections occur in newborns, although less commonly
than in older infants. The most commonly isolated virus is respiratory syncytial
virus (RSV). The transfer of maternal antibodies is important in protecting
newborns and young infants from such infections, making premature infants (who
may not have benefited from sufficient transfer of transplacental immunoglobulin
G [IgG]) especially vulnerable to lower-tract disease. In addition, premature
infants may have chronic lung disease of prematurity, with associated
hyperreactive airways, fewer functional alveoli, and baseline increased oxygen
requirements.
Infants and toddlers
o Viruses are the most common cause of pneumonia, accounting for approximately
90% of all lower respiratory infections.
o RSV is the most common viral pathogen, followed by parainfluenza types 1, 2,
and 3 and influenza A or B. RSV infection occurs in the winter and early spring.
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Parainfluenza type 3 infection occurs in the spring, and types 1 and 2 occur in the
fall. Influenza occurs in the winter.
o Other viruses that cause pneumonia less frequently in infants include adenovirus,
enterovirus, rhinovirus, coronavirus, herpesvirus, and cytomegalovirus. A recent
addition to this list is human metapneumovirus, which causes an illness similar to
RSV and may be responsible for one third to one half of non-RSV bronchiolitis.
o Bacterial infections in this age group are uncommon and are attributable to
Streptococcus pneumoniae, H influenzae type B (less common in immunized
children), or Staphylococcus aureus. Infants or toddlers with bacterial pneumonia
may present with lethargy, irritability, acidosis, hypotonia, or hypoxia that is out
of proportion to ausculatory findings.
o Children younger than 5 years, children enrolled in daycare, or those with
frequent ear infections are at increased risk for invasive pneumococcal disease
and infection with resistant pneumococcal strains. They are often treated with an
antibiotic within a month of contracting pneumonia.
o Evidence suggests that breastfeeding has a protective effect against invasive
pneumococcus.
Children aged 5 years (ready to start school)
o Mycoplasma pneumoniae is the most common cause of community-acquired
pneumonia and accounts for 20% of pneumonia cases in the general population,
9-16% of cases in early-school–aged children, 16-21% of cases in older children,
and 30-50% of cases in college students and military recruits.
o Mycoplasma infections are indolent, with gradual onset of malaise, low-grade
fever, headache, and cough. C pneumoniae is also fairly common in this age
group and presents in a similar fashion.
School-aged children and adolescents: Bacterial pneumonia (10%) is common, and these
children are often febrile and appear ill.
o Tuberculosis (TB) pneumonia in children warrants special mention.
o Children with TB usually do not present with symptoms until 1-6 months after
primary infection.
o Infants and postpubertal adolescents are at increased risk of disease progression.
These children may present with fever, night sweats, chills, cough (which may
include hemoptysis), and weight loss.
o Chest radiography findings may include hilar or mediastinal lymphadenopathy,
atelectasis, or consolidation of a segment or lobe (usually right upper lobe),
pleural effusion, cavitary lesions (in adolescents and adults only), or miliary
disease.
o A history of exposure to possible sources should be obtained (eg, immigrants
from Africa, certain parts of Asia, and Eastern Europe; contacts with persons in
the penal system; close contact with known individuals with TB).
o If TB is not treated during the early stages of infection, approximately 25% of
children younger than 15 years develop extrapulmonary disease.
Bordetella pertussis also causes pneumonia, although predominantly in infants who have not
completed their vaccinations or in children who did not receive vaccinations. Bronchopneumonia
occurs in 0.8-2% of all pertussis cases and 16-20% of hospitalized cases. The survival rate with
this complication is much lower than in pneumonia attributed to other causes. A study conducted
in the United Kingdom showed that 59% of deaths from pertussis are associated with
pneumonia. Clinical presentation includes coryza, malaise, fever, paroxysms of cough
occasionally accompanied by emesis, apnea, poor feeding, and cyanosis.
Viral pneumonias are common in this age group and are usually mild and self-limited. However,
as in adults, viral pneumonias are occasionally severe and can rapidly progress to respiratory
failure, either as a primary manifestation of viral infection or as a consequence of subsequent
bacterial infection. Group A streptococcal, pneumococcal, and staphylococcal secondary
infections are all relatively common.
Aspiration pneumonia is more common in children with neurological impairment and
swallowing abnormalities. Oral anaerobic flora, with or without aerobes, is the most common
etiologic agent.
In immunosuppressed individuals, opportunistic infections with organisms such as Aspergillus
species, Candida species, Pneumocystis species, and cytomegalovirus can occur.
Differential Diagnoses
Afebrile Pneumonia Syndrome
Agammaglobulinemia
Airway Foreign Body
Aspiration Syndromes
Asthma
B-Cell and T-Cell Combined Disorders
Bronchiectasis
Bronchiolitis
Bronchitis, Acute and Chronic
Chronic Granulomatous Disease
Coccidioidomycosis
Common Variable Immunodeficiency
Complement Deficiency
Complement Receptor Deficiency
Congenital Pneumonia
Cystic Adenomatoid Malformation
Cystic Fibrosis
Empyema
Gastroesophageal Reflux
Goodpasture Syndrome
Heart Failure, Congestive
Hemosiderosis
Histoplasmosis
Human Immunodeficiency Virus Infection
Hypersensitivity Pneumonitis
IgA and IgG Subclass Deficiencies
Inhalation Injury
Legionella Infection
Pertussis
Pneumococcal Infections
Pulmonary Sequestration
Q Fever
Workup
Laboratory Studies
Identifying the causative infectious agent is the most valuable step in managing a complicated
case of pneumonia. Unfortunately, an etiologic agent can be difficult to identify. Therefore, in
most patients with community-acquired pneumonia who are treated on an outpatient basis,
treatment is empiric and based primarily on patient age and clinical presentation.
In patients with complicated pneumonia who have not responded to treatment or who require
admission to the hospital, several diagnostic studies aimed at identifying the infectious culprit are
warranted, including cultures, serology, and a CBC count with the differential and acute-phase
reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]).
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Direct antigen detection
o Although antiviral therapies are not often used, performing a nasal wash for
respiratory syncytial virus (RSV) and influenza enzyme-linked immunoassay
(ELISA) and viral culture can help to establish a rapid diagnosis, which may be
helpful in excluding other diagnoses. In addition, correct diagnosis allows for
appropriate placement of patients in the hospital. For example, if necessary, 2
infants with RSV infection may share a room, whereas such patients would
normally need isolation and may unnecessarily tie up a bed.
o Viral cultures can be obtained in 1-2 days using newer cell culture techniques and
may permit discontinuation of unnecessary antibiotics.
Sputum culture
o Sputum is rarely produced in children younger than 10 years, and samples are
always contaminated by oral flora. An adequate sputum culture should contain
more than 25 polymorphonuclear (PMN) cells per field and fewer than 10
squamous cells per field.
o The common agents that cause pneumonia may be normal oral flora. For these
reasons, sputum cultures are not useful in most children with pneumonia,
although a Gram stain may help.
Bronchoscopy
o Flexible fiberoptic bronchoscopy is occasionally useful to obtain lower airway
secretions for culture or cytology.
o This procedure is most useful in immunocompromised patients who are believed
to be infected with unusual organisms (Pneumocystis, other fungi) or in patients
who are severely ill.
o Careful consideration of the diagnostic possibilities is necessary to send the
samples for the appropriate tests.
o Contamination of the bronchoscopic aspirate with upper airway secretions is
common; quantitative cultures can help distinguish contamination from infection.
Blood culture
o Although blood cultures are technically easy to obtain and relatively noninvasive
and nontraumatic, the results are rarely positive in the presence of pneumonia and
even less so in cases of pretreated pneumonia.
o In a study of 168 patients with known pneumonia, Wubbel et al found only sterile
blood cultures. In general, blood culture results are positive in 10-15% of patients
with streptococcal pneumonia (Media file 1).[2 ]The numbers are even less in
patients with Staphylococcus infection. A blood culture is still recommended in
complicated cases of pneumonia.
Lung aspirate
o This test is underused and is a significantly more efficient method of obtaining a
culture.
o
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A study that compared the incidence of (1) positive culture results obtained with
blood culture with (2) positive culture results obtained with lung aspiration in 100
children aged 3-58 months with pneumonia merits mention.[3 ]Blood culture
implicated an organism in 18% of the patients compared with 52% with lung
aspirate. The organisms obtained in the blood and lung aspirate differed in 4 of
the 8 children in whom both culture results were positive, suggesting that a blood
culture may not always accurately reveal the lung pathogen.
o Other studies have demonstrated lung aspirate results to be positive in 50-60% of
patients with known pneumonia. In these studies, 1.5-9% of patients had a
pneumothorax and 0.7-3% had transient small hemoptysis complicating their lung
aspirations. Because of the possible risks associated with lung aspiration, it should
be reserved for patients who are ill enough to require hospitalization, have not
improved with previous empiric treatment, or are immunocompromised and an
exact etiology is needed.
o A lung aspirate should not be performed in patients who are on ventilators,
patients with a bleeding diathesis, or in patients suspected of having an infection
with Pneumocystis.
Thoracentesis
o This test is performed for diagnostic and therapeutic purposes in children with
pleural effusions.
o If the Gram stain or the culture result from the pleural fluid is positive or the
WBC is higher than 1000 cells/mL, by definition, the patient has an empyema,
which may require drainage for complete resolution.
o Other therapeutic decisions can be made based on the properties of the effusion
(see Complications).
Serology
o Because of the relatively low yield of cultures, more efforts are underway to
develop quick and accurate serologic tests for common lung pathogens, such as M
pneumoniae.
o In a Finnish study, 278 patients diagnosed with community-acquired pneumonia
underwent extensive testing for Mycoplasma infection.[4 ]
 Acute and convalescent serum samples were collected and tested using
enzyme immunoassay for M pneumoniae immunoglobulin M (IgM) and
IgG antibodies. Nasopharyngeal aspirates were tested using PCR and
cultured with a Pneumofast kit.
 Positive results were confirmed with Southern hybridization of PCR
products and an IgM test with solid-phase antigen. A total of 24 (9%)
confirmed diagnoses of Mycoplasma infection were made. All 24 cases
had positive results with IgM-capture test with convalescent-phase serum.
Using an IgM-capture test in acute-phase serum, 79% of results were
positive, 79% were positive using IgG serology, 50% positive using PCR,
and 47% positive using culture.
 The authors of this study concluded that IgM serologic studies for
Mycoplasma infection were not only quick but also sensitive and were the
most valuable tools for diagnosis of M pneumoniae infection in any age
group. IgM serology is much more sensitive than cold agglutinin
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assessments, which are more commonly used to aid in the diagnosis of
Mycoplasma infection and demonstrate positive results in only 50% of
cases.
Polymerase chain reaction
o This test shows promise of being useful in diagnosing streptococcal pneumonia.
o PCR is noninvasive, an advantage over lung aspirate or bronchoalveolar lavage
(BAL) cultures. Similarly, C pneumoniae infection is diagnosed more readily with
PCR than with culture; however, positive test results must correlate with acute
symptoms to have any validity because 2-5% of the population may be
asymptomatically infected with C pneumoniae.
o Although new serologic and PCR tests for common lung pathogens hold definite
promise for making rapid, accurate, and noninvasive diagnosis, they are not
widely available, and the results may not return until after the patient has already
completed a course of antibiotics.
o Direct fluorescent antibody and serologic tests for RSV and influenza, as well as a
PCR test for tuberculosis (TB), are widely available and have proven to be of
considerable benefit in the treatment of hospitalized patients.
Skin tests
o These tests are used in diagnosing TB. Mantoux skin test (intradermal inoculation
of 5 TU of purified protein derivative) results should be read 48-72 hours after
placement.
o In children older than 4 years without any risk factors, test results are positive if
the induration (not the area of erythema, which may be larger) is 15 mm or larger.
Among children younger than 4 years, those who have an increased
environmental exposure to TB or other medical risk factors (eg, lymphoma,
diabetes mellitus, malnutrition, renal failure), results are positive if the induration
is 10 mm or larger. In immunosuppressed children or those in close contact with
others who have known or suspected cases of TB, test results are positive if the
induration is 5 mm or larger.
o Even if the child has received the Bacillus Calmette-Guérin (BCG) vaccine,
Mantoux test results should be interpreted using the criteria outlined above.
o Chest radiography helps to confirm the diagnosis of a child with positive Mantoux
test results. If the chest radiography findings are positive or if the child has other
symptoms consistent with the diagnosis of TB, an attempt should be made to
isolate the tubercle bacilli from early-morning gastric aspirates, cerebrospinal
fluid, sputum, urine, pleural fluid, or biopsy specimen.
o In a child with suspected pulmonary TB, the cough may be scarce or
nonproductive. Therefore, the best test for diagnosis is an early-morning gastric
aspirate sent for acid-fast bacilli (AFB) stain, culture, and, if available, PCR.
Gastric aspirates should be obtained by first placing a nasogastric (NG) tube the
night before sample collection; a sample is aspirated first thing the following
morning, before ambulation and feeding. This should be repeated on 3
consecutive mornings.
CBC count: Testing should include a CBC count with differential and evaluation of
acute-phase reactants (ESR, CRP, or both) and sedimentation rate. The total WBC and
differential may aid in determining if an infection is bacterial or viral, and, together with
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clinical symptoms, chest radiography and ESR can be useful in monitoring the course of
pneumonia.
ABG: This test is indicated in any patient with significant respiratory distress to
determine the degree of respiratory insufficiency.
Imaging Studies
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Radiography
o This is the primary imaging study used to confirm the diagnosis of pneumonia.
Radiography is often performed when diagnosing pneumonia; however, it is not
always necessary or useful in determining the etiology of the infection.
o Chest radiography is indicated in an infant or toddler who presents with fever and
any of the following: tachypnea, nasal flaring, retractions, grunting, rales,
decreased breath sounds, or respiratory distress. In older children and adolescents,
the diagnosis of pneumonia is often based on clinical presentation.
o Chest radiography is primarily indicated in complicated cases in which treatment
fails to elicit a response, in patients with respiratory distress, or in those who
require hospitalization. Obtain both frontal and lateral radiographs, particularly in
cases in which the clinical examination findings are equivocal. In complicated
cases of pneumonia, perform chest radiography 6 weeks after treatment to verify
resolution of the pneumonia and to screen for any underlying predisposing
conditions, such as sequestration.
o Although trends in radiographic findings may prove useful, chest radiography
findings frequently do not correlate with the infectious agent involved. Chest
radiography findings may be negative in the presence of pneumonia, particularly
early in the course. A lobar infiltrate can be seen with viral infections, foreign
body aspirations, and mucous plugging that results in atelectasis. Furthermore,
pleural effusions, although usually parapneumonic (80%), may be observed in
numerous disease processes.
o Several studies have demonstrated that chest radiography is 42-73% accurate in
predicting the etiology of a case of pneumonia. In one study of 168 children with
pneumonia, 2 radiologists who independently evaluated all chest radiographs
were unable to distinguish whether the agent involved was bacterial, viral, or
unidentified.[2 ]Given the frequency of nonspecific findings obtained with
imaging, clinical presentation and other laboratory findings must be considered in
the diagnosis of pneumonia and the determination of the etiologic agent.
o In general, viral pneumonias are associated with a patchy perihilar infiltrate,
hyperinflation, and atelectasis on chest radiography.
o In patients with bacterial pneumonia, typical findings include a lobar
consolidation with air bronchograms occasionally accompanied by a pleural
effusion (Media files 2-3). Pneumatoceles and abscesses are less commonly found
but may indicate an S aureus, gram-negative, or complicated pneumococcal
pneumonia.
o The radiographic appearance of Mycoplasma infection varies. Early in the
infection, the pattern tends to be reticular and interstitial; as the infection
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progresses, patchy and segmental areas of consolidation are noted, along with
hilar adenopathy and pleural effusions.
o Except for patients with sickle cell disease (SCD), a significant pleural effusion
usually indicates a bacterial etiology. Although these patterns are typical, the
etiology cannot be reliably identified based solely on chest radiography findings.
Ultrasonography
o These studies are indicated primarily in children with complications such as
pleural effusions and in those in whom antibiotic treatment fails to elicit a
response.
o Ultrasonography is used to effectively differentiate between a low-grade
(nonfibrinopurulent) effusion and one that is high-grade (fibrinopurulent and
organizing). In a study of children whose effusions were characterized as high
grade based on ultrasonography findings, hospital stay was reduced by nearly
50% after surgery.
o Ultrasonography may also prove useful for guidance in thoracentesis of a
loculated effusion. In addition to a pleural effusion or empyema, other
suppurative complications of pneumonia include cavitary necrosis or abscess and
purulent pericarditis. A significant number of these complications are not evident
using radiography.
Contrast CT scanning
o This test is also indicated in children with complications such as pleural effusions
and in those in whom antibiotic treatment fails to elicit a response.
o ContrastCT scanning is often more sensitive and demonstrates changes typical for
these complications. This information is beneficial when making treatment
decisions (eg, whether to perform surgical debridement of organized empyemas
or loculated effusions) and in outlining the projected course of the patient's
illness.
Procedures
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Bronchoscopy with BAL
Lung biopsy (guided with CT scanning or ultrasonography, as part of a video-assisted
thorascopic surgery [VATS] procedure, or during bronchoscopy) to assist in the diagnosis
of infection with rare or unusual organisms
Histologic Findings
No specific histologic findings are reported in most patients with pneumonias beyond evidence
of inflammation and cellular infiltration and exudation into alveolar spaces and the
interstitium. Sputum, lavage, or biopsy material may yield diagnostic findings.
o
In patients with TB, acid-fast bacilli are present and can be detected using the ZiehlNeelsen stain or can be grown on the Lowenstein-Jensen medium. Caseating granulomas
are highly suspicious, even in the absence of detectable organisms.
o
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Findings of foamy alveolar casts are practically diagnostic for Pneumocystis jiroveci
pneumonia, and the cup-shaped organisms are often found using Gomori methenamine
silver staining or direct immunofluorescence.
Fungal elements may be seen using Gomori methenamine silver staining or periodic acidSchiff staining. Aspergillus and Zygomycetes species may be seen using simple
hematoxylin and eosin staining. The specific morphology of the organisms may be
diagnostic, but, occasionally, culture or immunostaining is required.
Treatment
Medical Care
Treatment decisions in children with pneumonia are dictated based on the likely etiology of the
infectious organism and the age and clinical status of the patient. Antibiotic administration must
be targeted to the likely organism, bearing in mind the age of the patient, the history of exposure,
the possibility of resistance (which may vary, depending on local resistance patterns), and other
pertinent history.
Chest percussion is usually unnecessary in children with pneumonia. Studies in adults have not
shown benefit; however, no definitive studies have been performed in children. Although most
children do not expectorate sputum, they are able to clear it from their lungs and to swallow it. In
young infants with bronchiolitis, chest percussion can be helpful in moving mucus and
improving air entry (postpercussion auscultation often results in increased wheezes and crackles
because of the better air entry) and oxygenation. However, the few studies that have involved
children have not shown shortened hospital stays.
Bronchodilators should not be routinely used. Bacterial lower respiratory tract infections rarely
trigger asthma attacks, and the wheezing that is sometimes heard in patients with pneumonia is
usually caused by airway inflammation, mucus plugging, or both and is not bronchodilator
responsive. However, infants or children with reactive airway disease or asthma may react to a
viral infection with bronchospasm, which responds to bronchodilators. The role of steroids in
this situation is controversial, and steroids should probably not be initiated as routine because of
the lack of evidence that they are beneficial and because of the risk of immunosuppression.
A few small studies in adults suggest that glucocorticoid use might be beneficial in the treatment
of serious (hospitalized) community-acquired pneumonia, although the study designs and sizes
limit the ability to properly interpret this data.[5 ] Until definitive studies are performed, steroids
should not be routinely used for uncomplicated pneumonia. Extra humidification of inspired air
(eg, room humidifiers) is also not useful, although supplemental oxygen is frequently humidified
for patient comfort.
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School-aged children
o Many of these children do not require hospitalization and respond well to oral
antibiotics. Macrolide antibiotics are useful in this age group because they cover
the most common bacteriologic and atypical agents. However, increasing levels of
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resistance to macrolides among streptococcal isolates should be considered
(depending on local resistance rates).
o Usually, these patients are not toxic or hypoxic enough to require supplemental
oxygen. Unless they are vomiting, they do not require intravenous fluids or
antibiotics. A parapneumonic effusion that requires drainage usually dictates a
hospital admission.
Children younger than 5 years: These children are hospitalized more often, but their
clinical status, degree of hydration, degree of hypoxia, and need for intravenous therapy
dictate this decision.
Surgical Care
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Drainage of parapneumonic effusions with or without intrapleural instillation of a
fibrinolytic agent (eg, tissue plasminogen activator [TPA]) may be indicated.
Chest tube placement for drainage of an effusion or empyema may be performed.
VATS procedure may be performed for decortication of organized empyema or loculated
effusions.
Diet
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No specific dietary considerations are recommended. However, anorexia is commonly
associated with inflammatory conditions.
Activity
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Activity stimulates mucus mobilization, cough, and a resolution of the disease process.
Gentle activity should be encouraged. Even very young infants can benefit from
repositioning to help shift mucus.
Children usually do not participate in vigorous activity if they are ill and, in general, can
be trusted to limit their own activity when necessary.
Medication
Drug therapy for pneumonia is tailored to the situation. Because the etiologic agents vary, drug
choice is affected by the patient's age, exposure history, likelihood of resistance (eg,
pneumococcus), and clinical presentation. Macrolide antibiotics are useful in most school-aged
children to cover the atypical organisms and pneumococcus, but an immigrant child with a
positive purified protein derivative (PPD) of tuberculin needs a different drug. Local variations
in resistance require different approaches to therapy, including cases caused by pneumococcus.
Macrolide Antibiotics
These agents are used for treatment of pneumonia in school-aged children because they cover
most common bacteriologic and atypical agents.
Azithromycin (Zithromax)
Treats mild-to-moderate microbial infections.
Dosing
Adult
Day 1: 500 mg PO
Days 2-5: 250 mg PO qd
Pediatric
<6 months: Not established
>6 months:
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
Interactions
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with
coadministration of aluminum or magnesium antacids; nephrotoxicity and neurotoxicity may
occur when coadministered with cyclosporine
Contraindications
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic
enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged
QT intervals, or pneumonia; caution in patients who are hospitalized, elderly, or debilitated
Clarithromycin (Biaxin)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes
causing RNA-dependent protein synthesis to arrest.
Dosing
Adult
250-500 mg PO q12h for 7-14 d
Pediatric
7.5 mg/kg PO bid; not to exceed adult dose
Interactions
Toxicity increases with coadministration of fluconazole and pimozide; clarithromycin effects
decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may
increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole,
carbamazepine, ergot alkaloids, triazolam, HMG-CoA reductase inhibitors
Plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias
and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may
increase plasma levels of both agents
Contraindications
Documented hypersensitivity; coadministration of pimozide
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min;
give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of
pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic
therapies
Erythromycin (E.E.S., E-Mycin, Ery-Tab)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes
causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and
streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is
desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.
Dosing
Adult
250 mg erythromycin stearate/base (or 400 mg ethylsuccinate) q6h PO 1 h ac or 500 mg q12h
Alternatively, 333 mg q8h; increase to 4 g/d depending on severity of infection
Pediatric
30-50 mg/kg/d (15-25 mg/lb/d) PO divided q6-8h; double dose for severe infection
Interactions
Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and
cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin
and simvastatin increases risk of rhabdomyolysis; decreases metabolism of repaglinide,
increasing serum levels and effects
Contraindications
Documented hypersensitivity; hepatic impairment
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with liver disease; estolate formulation may cause cholestatic jaundice; GI
adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise,
abdominal colic, or fever occurs
Antibiotics for children younger than 5 years
These children are most commonly hospitalized, but their clinical status, degree of hydration,
degree of hypoxia, and need for intravenous antibiotic therapy dictate this decision.
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy
against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial
growth by binding to one or more penicillin-binding proteins.
Dosing
Adult
1-2 g IV qd or divided bid; not to exceed 4 g/d
Pediatric
Neonates >7 days: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Interactions
Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide,
and aminoglycosides may increase nephrotoxicity
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin
Cefotaxime (Claforan)
For infections caused by susceptible organisms. Arrests bacterial cell wall synthesis, which, in
turn, inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum.
Lower efficacy against gram-positive organisms.
Dosing
Adult
Moderate to severe infections: 1-2 g IV/IM q6-8h
Life threatening infections: 1-2 g IV/IM q4h
Pediatric
Infants and children: 50-180 mg/kg/d IV/IM divided q4-6h
>12 years: Administer as in adults
Interactions
Probenecid may increase cefotaxime levels; coadministration with furosemide and
aminoglycosides may increase nephrotoxicity
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe renal impairment; has been associated with severe colitis
Ampicillin (Marcillin, Omnipen, Polycillin)
Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to
take medication orally.
Dosing
Adult
250-500 mg PO q6h
500 mg to 1.5 g IM q4-6h
500 mg to 3 g IV q4-6h; not to exceed 12 g/d
Pediatric
50-100 mg/kg/d PO divided q4-6h
100-400 mg/kg/d IM/IV divided q4-6h
Interactions
Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and
has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in patients with renal failure; evaluate rash and differentiate from hypersensitivity
reaction
Cefuroxime (Zinacef, Ceftin, Kefurox)
Second-generation cephalosporin maintains gram-positive activity that first-generation
cephalosporins have; adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and
M catarrhalis. Condition of patient, severity of infection and susceptibility of microorganism
determines proper dose and route of administration.
Dosing
Adult
500 mg PO bid
750-1500 mg IV q8h
Pediatric
<3 months: 20-50 mg/kg/d IV divided q8-12h
>3 months: 250 mg PO bid; 100-150 mg/kg/d divided q8h
Adolescents: Administer as in adults
Interactions
Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking
cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase
nephrotoxicity in patient receiving potent diuretics (eg, loop diuretics); coadministration with
aminoglycosides increase nephrotoxic potential
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Administer half dose if CrCl is 10-30 mL/min and one-quarter dose if less than 10 mL/min;
fungal and microorganism overgrowth may occur with prolonged therapy
Antituberculars
These agents are used in the treatment of patients with TB. Antimycobacterial agents are a
miscellaneous group of antibiotics whose spectrum of activity includes Mycobacterium species.
They are used to treat TB, leprosy, and other mycobacterial infections.
Isoniazid (Laniazid, Nydrazid)
Best combination of effectiveness, low cost, and minor side effects. First-line drug unless patient
has known resistance or another contraindication. Therapeutic regimens of <6 mo demonstrate
unacceptably high relapse rate.
Coadministration of pyridoxine is recommended if peripheral neuropathies secondary to
isoniazid therapy develop. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended.
Dosing
Adult
5 mg/kg PO qd (usually 300 mg/d) and 10 mg/kg qd in 1-2 divided doses in patients with
disseminated disease; not to exceed 300 mg/d
Directly observed therapy: 15 mg/kg twice weekly; not to exceed 900 mg/dose
Pediatric
10-15 mg/kg PO qd; not to exceed 300 mg/d
Directly observed therapy: 20-30 mg/kg PO twice weekly; not to exceed 900 mg/dose
Interactions
Higher incidence of isoniazid-related hepatitis can occur with alcohol ingestion on daily basis;
aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum
salts); may increase anticoagulants effects with coadministration; may inhibit metabolic
clearance of benzodiazepines
Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor
carbamazepine concentrations and liver function); coadministration with cycloserine may
increase CNS side effects (eg, dizziness); acute behavioral and coordination changes may occur
with coadministration of disulfiram
Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and
hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of
hydantoin
Contraindications
Documented hypersensitivity; previous isoniazid-associated hepatic injury or other severe
adverse reactions
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Monitor patients with active chronic liver disease or severe renal dysfunction; periodic
ophthalmologic examinations during isoniazid therapy are recommended, even when visual
symptoms do not occur
Ethambutol (Myambutol)
Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell
metabolism by inhibiting synthesis of one or more metabolites, which, in turn, causes cell death.
No cross-resistance demonstrated.
Mycobacterial resistance is common with previous therapy. Use in these patients in combination
with second-line drugs that have not been previously administered.
Administer q24h until permanent bacteriological conversion and maximal clinical improvement
observed. Absorption is not significantly altered by food.
Dosing
Adult
No previous antituberculous therapy: 15 mg/kg (7 mg/lb) PO qd
Previous antituberculous therapy: 25 mg/kg (11 mg/lb) PO qd
Maximum dose is weight and regimen dependent, consult with infectious disease specialist
Pediatric
<13 years: Not recommended unless resistant to rifampin or isoniazid
>13 years: Administer as in adults
Interactions
Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol
dose)
Contraindications
Documented hypersensitivity; optic neuritis (unless clinically indicated)
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Reduce dose in impaired renal function; may cause optic neuritis or atrophy; baseline and
monthly visual acuity monitoring recommended in CDC guidelines; may have reversible visual
adverse effects if promptly discontinued
Rifampin (Rifadin, Rimactane)
For use in combination with at least one other antituberculous drug. Inhibits RNA synthesis in
bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks
RNA transcription.
Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum culture negativity.
Dosing
Adult
600 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV; not to exceed 600 mg/d
Interactions
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral
anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral
contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens,
hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines,
tocainide, and digoxin; blood pressure may increase with coadministration of enalapril;
coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent
alone (discontinue one or both agents if alterations in LFT findings occur)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Obtain CBC count and baseline clinical chemistries before and throughout therapy; in patients
with liver disease, weigh benefits against risk of further liver damage; interruption of therapy and
high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy
is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance
of purpura, cerebral hemorrhage or death may occur; may cause orange discoloration of urine or
secretions
Streptomycin sulfate
Use in combination with other antituberculous drugs (eg, isoniazid, ethambutol, rifampin). Total
period of treatment for TB is a minimum of 1 y; however, indications for terminating
streptomycin therapy may occur at any time. Recommended when less potentially hazardous
therapeutic agents are ineffective or contraindicated.
Dosing
Adult
1 g IM qd
2 times/wk dosing: 15 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d
Pediatric
2 times/wk dosing: 20-40 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d
Interactions
Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins,
amphotericin B, and loop diuretics
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index; not intended for long-term therapy; extreme caution in patients with
renal failure who are not on dialysis; caution with myasthenia gravis, hypocalcemia, and
conditions that depress neuromuscular transmission; may cause auditory and vestibular toxic
effects
Pyrazinamide
Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against
Mycobacterium tuberculosis, depending on concentration of drug attained at site of infection;
mechanism of action is unknown.
Administer for initial 2 mo of a 6-mo or longer treatment regimen for patients who are drug
susceptible. Treat patients who are drug resistant with individualized regimens.
Dosing
Adult
15-30 mg/kg PO qd; not to exceed 2 g/d
Indirectly observed therapy: 50-70 mg/kg PO
2 times/wk, not to exceed 4 g/d; alternatively, 50-70 mg/kg 3 times/wk, not to exceed 3 g/d
Pediatric
Administer as in adults
Interactions
Coadministration with rifampin may result in higher rate of hepatotoxicity than with either agent
alone (discontinue if alterations in LFT findings occur)
Contraindications
Documented hypersensitivity; severe hepatic damage; acute gout
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Use only in combination with other effective antituberculous agents; inhibits renal excretion of
urates; may result in hyperuricemia (usually asymptomatic); assess baseline serum uric acid;
discontinue drug upon signs of hyperuricemia with acute gouty arthritis; perform baseline LFTs
(closely monitor in liver disease); discontinue pyrazinamide upon signs of hepatocellular
damage; caution in history of diabetes mellitus
Antiviral agents
These agents must be initiated early to adequately inhibit the replicating virus. This is difficult
because the clinical situation usually deteriorates over several days, such that by the time the
child's condition is poor enough to require medical attention, the window of opportunity has
passed.
Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009
influenza season. The US Centers for Disease Control and Prevention (CDC) has issued revised
interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data
from a limited number of states indicate the prevalence of influenza A (H1N1) virus strains
resistant to oseltamivir (Tamiflu) is high. Because of this, zanamivir (Relenza) is recommended
as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure
is suspected. A second-line alternative is a combination of oseltamivir plus rimantadine, rather
than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the
physician regarding antiviral agent choice.
Influenza A viruses, including two subtypes (H1N1) and (H3N2), and influenza B viruses
currently circulate worldwide, but the prevalence can vary among communities and within a
single community over the course of an influenza season. In the United States, 4 prescription
antiviral medications (oseltamivir, zanamivir, amantadine and rimantadine) are approved for
treatment and chemoprophylaxis of influenza. Since January 2006, the neuraminidase inhibitors
(oseltamivir, zanamivir) have been the only recommended influenza antiviral drugs because of
widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2)
virus strains. The neuraminidase inhibitors have activity against influenza A and B viruses,
whereas the adamantanes have activity only against influenza A viruses.
In 2007-08, a significant increase in the prevalence of oseltamivir resistance was reported among
influenza A (H1N1) viruses worldwide. During the 2007-08 influenza season, 10.9% of H1N1
viruses tested in the United States were resistant to oseltamivir.
Complete recommendations are available from the CDC.
Ribavirin (Virazole)
Inhibits viral replication by inhibiting DNA and RNA synthesis. Antiviral against RSV,
influenza virus, and herpes simplex virus. Little evidence has been found to demonstrate that it
has much clinical benefit in a hospital setting.
Dosing
Adult
Reconstitute 6 g into 300 mL of sterile water to make a concentration of 20 mg/mL
Administer as continuous aerosol over 12-18 h/d for 3-7 d
Pediatric
Administer as in adults
Interactions
Decreases zidovudine effects
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Closely monitor patients with asthma for deterioration of respiratory function
Oseltamivir (Tamiflu)
Inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an
infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, it decreases
release of viruses from infected cells and, thus, viral spread. Effective for treatment of influenza
A or B infection. Start within 40 h of symptom onset. Available as capsules and as an oral susp.
Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009
influenza season. The CDC has issued revised interim recommendations for antiviral treatment
and prophylaxis of influenza. Preliminary data from a limited number of states indicate that the
prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu) is high.
Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral
prophylaxis or treatment when influenza A infection or exposure is suspected. A second-line
alternative is a combination of oseltamivir plus rimantadine, rather than oseltamivir alone. Local
influenza surveillance data and laboratory testing can assist the physician regarding antiviral
agent choice.
Dosing
Adult
Acute illness: 75 mg PO bid for 5 d
Prophylaxis: 75 mg PO qd for 10 d
Pediatric
Acute illness
<1 year: Not indicated
>1 year:
<15 kg: 30 mg PO bid for 5 d
>15-23 kg: 45 mg PO bid for 5 d
>23-40 kg: 60 mg PO bid for 5 d
>40 kg: Administer as in adults
Prophylaxis:
<1 year: Not established
>1 year:
<15 kg: 30 mg PO qd for 10 d
>15-23 kg: 45 mg PO qd for 10 d
24-40 kg: 60 mg PO qd for 10 d
>40 kg: Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment, chronic cardiac or respiratory disease, and breastfeeding; do not use
in children <1 y (preclinical trials have demonstrated death in young animals, possibly related to
immature blood-brain barriers); postmarketing reports (mostly from Japan) of self-injury and
delirium in patients with influenza (reports primarily among children), unknown if oseltamivir
directly contributes to this behavior (monitor for abnormal behavior throughout treatment period)
Zanamivir (Relenza)
Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that
destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase,
release of viruses from infected cells and viral spread are decreased. Effective against both
influenza A and B. To be inhaled through Diskhaler oral inhalation device. Circular foil discs
that contain 5-mg blisters of drug are inserted into supplied inhalation device.
Dosing
Adult
Treatment: 10 mg (2 inhalations, 5 mg/inhalation) inhaled PO q12h for 5 d; initiate within 2 d of
symptom onset
Prophylaxis: 10 mg (2 inhalations, 5 mg/inhalation) inhaled PO qd for 10 d; initiate within 36 h
of exposure
Pediatric
Treatment:
<7 years: Not established
>7 years: Administer as in adults
Prophylaxis:
<5 years: Not established
>5 years: Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity; obstructive airway disease
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions
Monitor respiratory status; may cause bronchospasm; caution in breastfeeding
Follow-up
Further Outpatient Care
If therapy fails to elicit a response, the whole treatment approach must be reconsidered. After
initiating therapy, the most important tasks are resolving the symptoms and clearing the
infiltrate. With successful therapy, symptoms resolve much sooner that the infiltrate. In a study
of adults with pneumococcal pneumonia, the infiltrate did not completely resolve in all patients
until 8 weeks after therapy (although it was sooner in most patients).
In a patient who is clinically doing well, follow-up radiography should be performed after 8
weeks. Although some pneumonias are destructive (eg, adenovirus) and can cause permanent
changes, most childhood pneumonias have complete radiologic clearing. If a significant
abnormality persists, consideration of an anatomic abnormality is appropriate.
Transfer
Severe respiratory compromise may require intubation and transfer to a suitable ICU for more
intensive monitoring and therapy. Indications for transfer include refractory hypoxia,
decompensated respiratory distress (eg, lessening tachypnea due to fatigue, hypercapnia), and
systemic complications such as sepsis. Transfer may need to be initiated at a lower threshold for
infants or young children, as decompensation may be rapid. Transfer of very sick infants or
young children to a pediatric ICU is best done with a specialist pediatric transfer team, even if
that entails a slightly longer wait, compared with conventional medical transport or even air
transport.
Deterrence/Prevention
Aside from avoiding infectious contacts (difficult for many families who use daycare facilities),
vaccination is the primary mode of prevention. Since the introduction of the conjugated H
Influenzae type B (HIB) vaccine, the rates of HIB pneumonia have significantly declined.
However, it should still be considered in unvaccinated persons, including those younger than 2
months, who have not received their first shot.
Conjugated and unconjugated polysaccharide vaccines for S pneumoniae have been developed
for infants and children, respectively. The pneumococcal 7-valent conjugate vaccine (diphtheria
CRM197 protein; Prevnar) contains epitopes to 7 different strains. Pneumococcal vaccine
polyvalent (Pneumovax) covers 23 different strains.
Influenza vaccine is recommended for children aged 6 months and older. The vaccine exists in 2
forms: inactivated vaccine (various products), administered as an intramuscular injection, and a
cold-adapted attenuated vaccine (FluMist [made by MedImmune]), administered as a nasal
spray, which is currently licensed only for persons aged 2-49 years.
Although the vaccine is especially recommended for children at high risk, such as those with
bronchopulmonary dysplasia (BPD), cystic fibrosis, or asthma, the use of FluMist is cautioned in
persons with known asthma because of reports of transient increases in wheezing episodes in the
weeks after administration. However, in years when vaccine strains have been mismatched with
the circulating influenza strains, FluMist has provided good protection (approximately 70%),
even when the inactivated vaccine was entirely useless.
Clinical trials are ongoing to lower the age of administration of Fluzone (made by Aventis
Pasteur), one of the inactivated intramuscular vaccines, to 2 months (currently approved for
children 6 months or older) to help protect this high-risk, but unvaccinated, population. The
safety and efficacy of this approach remains unknown.
Respiratory syncytial virus (RSV) prophylaxis consists of monthly intramuscular injections of a
monoclonal humanized antibody, palivizumab (Synagis [made by MedImmune]) at a dose of 15
mg/kg (maximum volume 1 mL per injection; multiple injections may be required per dose).
Monthly injections during the RSV season approximately halve the rate of serious RSV disease
that leads to hospitalization. This expensive therapy is generally restricted to infants at high-risk,
such as children younger than 2 years with chronic lung disease of prematurity, premature
infants younger than 6 months (or with other risk factors), and children with significant
congenital heart disease.
A new monoclonal antibody (motavizumab [Numax; also made by MedImmune]) is in phase III
clinical trials for similar indications and, if approved, will likely replace Synagis. In an
worldwide comparison between Numax and Synagis during the 2004-2006 RSV seasons, Numax
showed a 26% improvement in preventing hospitalizations due to RSV and a 52% reduction in
outpatient medically attended lower-tract RSV infections compared with Synagis. Numax
remains an investigational drug at this time with no plans for licensure for the 2007-2008 RSV
season.
Synagis has no role in the treatment of RSV infection. One study of intubated patients showed a
reduction in viral titers but no change in clinical status, perhaps reflective of a large
inflammatory component to the disease process. In addition, Synagis has not been shown to
reduce upper-respiratory infections with RSV. It reduces only the serious complications of
infection. Preliminary results from animal and small-scale human studies suggest that Numax
may be effective in reducing RSV viral load in the upper and lower airways. Clinical studies to
evaluate the safety and efficacy of Numax in the setting of treating RSV infection in hospitalized
children are ongoing.
Complications
A thin layer of fluid (approximately 10 mL) is usually found between the visceral and parietal
pleura and helps prevent friction. This pleural fluid is produced at 100 mL/h. Ninety percent of
the fluid is reabsorbed on the visceral surface, and 10% is reabsorbed by the lymphatics. Pleural
fluid accumulates when the balance between production and reabsorption is disrupted. A
transudate accumulates in the pleural cavity when changes in the hydrostatic or oncotic pressures
are not accompanied by changes in the membranes. Increased membrane permeability and
hydrostatic pressure often result from inflammation and result in a subsequent loss of protein
from the capillaries and an accumulation of exudates in the pleural cavity.
When a child with pneumonia develops a pleural effusion, thoracentesis should be performed
for diagnostic and therapeutic purposes. The pleural fluid should be obtained to assess pH and
glucose levels and a Gram stain and culture, CBC count with differential, and protein assessment
should be performed. Amylase and lactase dehydrogenase (LDH) levels can also be measured
but are less useful in a parapneumonic effusion than effusions of other etiologies. The results are
helpful in determining if the effusion is a transudate or exudate and help to determine the best
course of management for the effusion.
Severe coughing, especially in the context of necrotizing pneumonias or bullae formation, may
lead to spontaneous pneumothoraces. These may or may not require treatment depending on the
size of the pneumothorax and whether it is under tension and compromising ventilation and
cardiac output.
Prognosis
Overall, the prognosis is good. Long-term alteration of pulmonary function is rare, even in
children with pneumonia that has been complicated by empyema or lung abscess. Significant
sequelae occur with adenoviral disease, including bronchiolitis obliterans. Death almost
exclusively occurs in children with underlying conditions, such as chronic lung disease of
prematurity, congenital heart disease, and immunosuppression.
Patient Education
For excellent patient education resources, visit eMedicine's Pneumonia Center. Also, see
eMedicine's patient education articles Viral Pneumonia and Bacterial Pneumonia.
Miscellaneous
Medicolegal Pitfalls
Consideration of the patient's clinical condition, the likely organisms, local resistance patterns,
and history of confounding factors (eg, foreign body aspiration) helps in avoiding medical/legal
issues. The prime consideration for long-term management is follow-up radiography to ensure
that the infiltrate completely clears and no underlying lung abnormality is present. Patients with
respiratory syncytial virus (RSV) infections commonly have a relatively high neutrophil
percentage and thrombocytosis, which can mislead one to consider a bacterial infection.
Special Concerns
Occasionally, a patient has pneumonia that continues to manifest clinically, radiographically (eg,
8 wk after antibiotic treatment), or both despite adequate medical management. Other patients
may present with a history of recurrent pneumonias, defined as more than one episode per year
or more than 3 episodes in a lifetime.
These patients merit special mention because they require a more extensive workup by a
specialist. One useful way to categorize these patients is based on radiography findings with and
without symptoms. This method places these children in 1 of 3 categories (see Table) that help
narrow the differential diagnoses.
A careful history and examination are helpful to further narrow the differential diagnoses.
However, more testing is often needed to confirm most of these diagnoses and is generally
outside the scope of a primary care provider.
Categorizing Patients Based on Symptoms, Which Assists in Differential Diagnoses of Those
With Recurrent Pneumonias
Category Laboratory and
Clinical Findings Differential Diagnoses
Imaging Findings
Persistent or recurrent Persistent or
Cystic fibrosis, immunodeficiencies,
radiologic findings
recurrent fever and obstruction (intrinsic [eg, foreign body]
symptoms
or extrinsic [eg, compressing nodes or
1
Persistent radiologic No clinical
findings
findings
tumor]), pulmonary sequestration,
bronchial stenosis, or bronchiectasis
Anatomic abnormality (eg, sequestration,
fibrosis, pleural lesion)
2
Recurrent pulmonary No clinical
infiltrates
findings
with interval
radiologic clearing
3
Asthma and atelectasis that has been
misdiagnosed as a bacterial pneumonia;
aspiration syndrome, hypersensitivity
pneumonitis, idiopathic pulmonary
hemosiderosis, or a mild
immunodeficiency disorder
Some children who are immunocompromised, whether secondary to AIDS, an immune disorder,
or drug-induced, are at risk for pneumonias with opportunistic agents. Such opportunistic agents
include the following:
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Pneumocystis carinii pneumonia (PCP): PCP infection is common in this population of
children and can lead to respiratory failure in those who are profoundly
immunocompromised. PCP prophylaxis with trimethoprim-sulfamethoxazole 3 times a
week is widely used and has all but eradicated this organism in patients receiving
prophylaxis. If a child with immunosuppression contracts PCP infection, treatment with
trimethoprim-sulfamethoxazole is increased to twice daily.
Toxoplasmosis: This opportunistic agent is occasionally found in children who are
immunocompromised.
Varicella-zoster virus: Children who are immunocompromised and have been exposed to
varicella should receive varicella-zoster intravenous immunoglobulin and acyclovir.
Herpes simplex virus: This is treated with acyclovir.
Adenovirus: Infections can lead to bronchiolitis obliterans or hyperlucent lung syndrome
in children who are immunocompetent or immunocompromised.
Cytomegalovirus: This opportunistic agent poses a great risk to patients who are
immunocompromised and is difficult to treat.
Aspergillus and Zygomycetes species: Fungal infections occur in patients who undergo
prolonged hospitalization, have neutropenia, and receive broad-spectrum antibiotics.
Antifungal therapy is usually amphotericin (intravenous and nebulized).
Acute chest syndrome (ACS) occurs in 15-43% of patients with SCD. Infection or pneumonia is
the most common cause of ACS and is characterized by fever, chest pain, dyspnea, cough,
tachypnea, crackles, and an infiltrate on chest radiography.
The most common pathogens in the lungs of a patient with sickle cell disease (SCD) are viruses
and atypical agents, such as Mycoplasma or Chlamydia species. Patients with SCD have
problems with their complement system and have functional asplenia, which predisposes them to
infection with encapsulated organisms such as S pneumoniae and H influenzae type B. However,
the pneumococcal and HIB vaccines and penicillin prophylaxis have helped reduce the incidence
of bacterial infections.
Many patients referred for evaluation by specialists for recurrent pneumonia are diagnosed with
asthma. In emergency department studies, 35% of children with an asthma exacerbation have
abnormalities visible on chest radiographs. In a child not yet diagnosed with asthma, these
abnormalities are frequently interpreted as pneumonia. The right middle lobe is the most
common site, but any part of the lung may be affected. Abnormalities found on chest
radiography are usually the result of airway inflammation but do not require antibiotics.
Inflammation, often triggered by viral infection, is part of the asthmatic response. Wheezing
responsive to bronchodilators, a history of atopy, a family history of asthma, and a history of
cough or wheeze with exercise may be helpful in identifying these patients.
Multimedia
Media file 1: (A) Gram stain demonstrating gram-positive cocci in pairs and chains and (B)
culture positive for Streptococcus pneumoniae.
Media file 2: Right lower lobe consolidation in a patient with bacterial pneumonia.
Media file 3: A patient with bacterial pneumonia (same patient as in Media file 2) a few
days later. This radiograph reveals progression of pneumonia into the right middle lobe
and the development of a large parapneumonic pleural effusion.
Media file 4: A breakdown of test results and recommended treatment for pneumonia with
effusion.