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Pediatric Pneumonia Medication

Updated: Mar 14, 2017 Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor:
Russell W Steele, MD

Practice Essentials
The United Nations Children's Fund (UNICEF) estimates that pediatric pneumonia kills 3 million
children worldwide each year. These deaths occur almost exclusively in children with underlying
conditions, such as chronic lung disease of prematurity, congenital heart disease, and
immunosuppression. Although most fatalities occur in developing countries, pneumonia (see the
image below) remains a significant cause of morbidity in industrialized nations.

Right lower lobe consolidation in a patient


with bacterial pneumonia.
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Signs and symptoms

Pneumonia can occur at any age, although it is more common in younger children. Pneumonia
accounts for 13% of all infectious illnesses in infants younger than 2 years.
Newborns with pneumonia commonly present with poor feeding and irritability, as well as
tachypnea, retractions, grunting, and hypoxemia. Infections with group B Streptococcus, Listeria
monocytogenes, or gram-negative rods (eg, Escherichia coli, Klebsiella pneumoniae) are common
causes of bacterial pneumonia. Group B streptococci infections are most often transmitted to the
fetus in utero. The most commonly isolated virus is respiratory syncytial virus (RSV).

Cough is the most common symptom of pneumonia in infants, along with tachypnea, retractions,
and hypoxemia. These may be accompanied by congestion, fever, irritability, and decreased
feeding. Streptococcus pneumoniae is by far the most common bacterial pathogen in infants aged
1-3 months.

Adolescents experience similar symptoms to younger children. They may have other constitutional
symptoms, such as headache, pleuritic chest pain, and vague abdominal pain. Vomiting, diarrhea,
pharyngitis, and otalgia/otitis are also common in this age group. Mycoplasma pneumoniae is the
most frequent cause of pneumonia among older children and adolescents.

See Clinical Presentation for more detail.

Diagnosis

The signs and symptoms of pneumonia are often nonspecific and widely vary based on the
patients age and the infectious organisms involved.

Observing the childs respiratory effort during a physical exam is an important first step in
diagnosing pneumonia. The World Health Organization (WHO) respiratory rate thresholds for
identifying children with pneumonia are as follows:

Children younger than 2 months: Greater than or equal to 60 breaths/min


Children aged 2-11 months: Greater than or equal to 50 breaths/min
Children aged 12-59 months: Greater than or equal to 40 breaths/min

Assessment of oxygen saturation by pulse oximetry should be performed early in the evaluation
when respiratory symptoms are present. Cyanosis may be present in severe cases. Capnography
may be useful in the evaluation of children with potential respiratory compromise.

Other diagnostic tests may include the following:

Auscultation by stethoscope
Cultures
Serology
Complete blood cell count (CBC)
Chest radiography
Ultrasonography

New data show that point-of-care ultrasonography accurately diagnoses most cases of pneumonia
in children and young adults. Ultrasonography may eventually replace x-rays for diagnosis. [1, 2]
See Workup for more detail.

Management

Initial priorities in children with pneumonia include the identification and treatment of respiratory
distress, hypoxemia, and hypercarbia. Grunting, flaring, severe tachypnea, and retractions should
prompt immediate respiratory support. Children who are in severe respiratory distress should
undergo tracheal intubation if they are unable to maintain oxygenation or have decreasing levels
of consciousness. Increased respiratory support requirements such as increased inhaled oxygen
concentration, positive pressure ventilation, or CPAP are commonly required before recovery
begins.

Antibiotics

The majority of children diagnosed with pneumonia in the outpatient setting are treated with oral
antibiotics. High-dose amoxicillin is used as a first-line agent for children with uncomplicated
community-acquired pneumonia. Second- or third-generation cephalosporins and macrolide
antibiotics such as azithromycin are acceptable alternatives. Combination therapy (ampicillin and
either gentamicin or cefotaxime) is typically used in the initial treatment of newborns and young
infants.

Hospitalized patients can also usually be treated with a narrow-spectrum penicillin such as
ampicillin. The choice of agent and dosing may vary based on local resistance rates (high rates of
intermediate or resistant pneumococcus may require higher dosing of ampicillin to surmount the
altered penicillin-binding protein that is the cause of resistant pneumococcus). In areas where
resistance is very high (>25% of strains being nonsusceptible), a third-generation cephalosporin
might be indicated instead. Older children, in addition, may receive a macrolide to cover for
atypical infections.

Although the fluoroquinolones would cover all the common respiratory pathogens of childhood,
they are not approved for this indication and have significant potential adverse effects, including
short-term tendon damage and long-term impact on antibiotic resistance. They should be reserved
for cases in which other therapies have failed and ideally should be used after consultation with an
infectious disease specialist with whom other options, or alternative diagnoses, can be considered.

Children who are toxic appearing should receive antibiotic therapy that includes vancomycin
(particularly in areas where penicillin-resistant pneumococci and methicillin-resistant S aureus
[MRSA] are prevalent) along with a second- or third-generation cephalosporin.

Vaccines

Aside from avoiding infectious contacts (difficult for many families who use daycare facilities),
vaccination is the primary mode of prevention. Influenza vaccine is recommended for children
aged 6 months and older. The pneumococcal conjugate vaccine (PCV13) is recommended for all
children younger than 59 months old. The 23-valent polysaccharide vaccine (PPV23) is
recommended for children 24 months or older who are at high risk of pneumococcal disease.
See Treatment and Medication for more detail.

Background
Pneumonia and other lower respiratory tract infections are the leading causes of death worldwide.
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 are important. Although in developed countries the
diagnosis is usually made on the basis of radiographic findings, the World Health Organization
(WHO) has defined pneumonia solely on the basis of clinical findings obtained by visual
inspection and on timing of the respiratory rate. (See Clinical Presentation.)

Pneumonia may originate in the lung or may be a focal complication of a contiguous or systemic
inflammatory process. Abnormalities of airway patency as well as alveolar ventilation and
perfusion occur frequently due to various mechanisms. These derangements often significantly
alter gas exchange and dependent cellular metabolism in the many tissues and organs that
determine survival and contribute to quality of life. Recognition, prevention, and treatment of these
problems are major factors in the care of children with pneumonia. (See Pathophysiology.)

One particular form of pneumonia present in the pediatric population, congenital pneumonia,
presents within the first 24 hours after birth. For more information, see Congenital Pneumonia.

Other respiratory tract diseases such as croup (laryngotracheobronchitis), bronchiolitis, and


bronchitis are beyond the scope of this article and are not discussed further.

Pathophysiology
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.

Respiratory tract host defenses

To prevent and minimize injury and invasion by microorganisms and foreign substances, various
defense mechanisms have evolved, both systemically and within the respiratory tract. Some
mechanisms are nonspecific and are directed against any invasive agent, whereas others are
targeted against only microbes or substances with specific antigenic determinants. Many of the
defenses are compromised in the fetus and newborn infant, resulting in more frequent breaches
and consequent disruption of normal lung structure and function. [3]

Nonspecific defenses include the glottis and vocal cords, ciliary escalator, airway secretions,
migratory and fixed phagocytes, nonspecific antimicrobial proteins and opsonins, and the normal
relatively nonpathogenic airway flora. Anatomic structures of the upper airway and associated
reflexes discourage particulate material from entering, whereas coordinated movement of the
microscopic cilia on the tracheal and bronchial epithelia tends to sweep particles and mucus up the
airway and away from the alveoli and distal respiratory structures.

Mucoid airway secretions provide a physical barrier that minimizes epithelial adhesion and
subsequent invasion by microorganisms. These secretions typically contain complement
components, fibronectin, and other proteins that bind to microbes and render them more
susceptible to ingestion by phagocytes. Alveolar and distal airway secretions also include whole
surfactant, which facilitates opsonization and phagocytosis of pathogens, as well as surfactant-
associated proteins A (Sp-A) and D (Sp-D), both of which modulate phagocytosis, phagocyte
production of oxyradicals, and cytokine elaboration.

The secretions also contain directly inhibitory and microbicidal agents, such as iron-binding
proteins, lysozymes, and defensins. Typical benign airway commensals, such as alpha-hemolytic
streptococci and coagulase-negative staphylococci, occupy mucosal sites and elaborate
bacteriocins and other substances that prevent more pathogenic organisms from adhesion,
replication, and possible opportunistic invasion.

Newborns typically have sterile respiratory mucosa at birth, with subsequent uncontested
colonization by microorganisms from the mother or environment. Accelerated access to distal
respiratory structures and bypass of much of the ciliary escalator occur in infants who require
endotracheal intubation. In these infants, increased physical disruption of epithelial and mucous
barriers also occurs. In addition, interventional exposure to high oxygen concentrations, generous
airway pressures, and large intrapulmonary gas volumes may interfere with ciliary function and
mucosal integrity. The use of less invasive means of respiratory support, such as nasal ventilation,
nasal continuous positive airway pressure (CPAP), and nasal cannula (conventional or humidified,
high flow), may produce lesser degrees of pulmonary mucosal and parenchymal disruption, but
some disruption is almost always present.

Systemic host defenses

Immunologic defense mechanisms targeted against particular pathogens typically emanate from
specifically primed lymphocytes following presentation of processed antigens by macrophages.
These mechanisms include cytotoxic, killer, suppressor, and memory functions; systemic and
secretory antibodies; and consequent cascades of cytokines, complement, vasomotor regulatory
molecules, hemostatic factors, and other agents. Secretory antibodies are typically multimeric and
contain secretory component and J chains that render them more opsonic and more resistant to
microbial proteases.

Many of the biochemical cascades triggered by specific immune responses serve to localize
microbial invasion, amplify and focus recruitment of phagocytes to the affected sites, and directly
disrupt the structural and metabolic integrity of the microbes. The role that these cascades play in
triggering apoptosis (programmed cell death) in host and invader cells is still undergoing
exploration.
Secretory antibodies and mucosal lymphoid tissue are absent or minimally functional for the first
month of life postnatally. Systemic antibodies may enter pulmonary tissues but usually consist
primarily of passively transmitted maternal antibodies, with reduced transplacental transport of
maternal antibodies before 32 weeks' gestation. Specific systemic antibodies can be generated, but
many components of the necessary immunologic machinery are relatively sluggish. Circulating
complement components are present at approximately 50% of the concentration found in older
children, although components of the alternative pathway are present in sufficient quantities to
serve as effective opsonins.

The neonatal granulocyte number frequently decreases in response to early infection (as well as
noninflammatory processes such as maternal preeclampsia), whereas the phagocytes that are
present often move much more sluggishly to the inflammatory focus, whether it is a microorganism
or inanimate debris. Once at the targeted sites, phagocytes often ingest the invaders less efficiently,
although intracellular microbicidal activities appear normal. Intercellular communication via
cytokines and other mediators is blunted.

The net result of these and other developmental aberrations is that the fetal and neonatal
inflammatory response is slower, less efficient, and much less focused than in older children.
Infection is less likely to be localized and effectively inhibited by host defenses alone.
Inflammation from particulate debris and other foreign substances is isolated less effectively, and
the injurious effector portions of the inflammatory cascade are much less precisely targeted.

Pathogenesis

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.

The activated inflammatory response often results in targeted migration of phagocytes, with the
release of toxic substances from granules and other microbicidal packages and the initiation of
poorly regulated cascades (eg, complement, coagulation, cytokines). These cascades may directly
injure host tissues and adversely alter endothelial and epithelial integrity, vasomotor tone,
intravascular hemostasis, and the activation state of fixed and migratory phagocytes at the
inflammatory focus. The role of apoptosis (noninflammatory programmed cell death) in
pneumonia is poorly understood.

Pulmonary injuries are caused directly and/or indirectly by invading microorganisms or foreign
material and by poorly targeted or inappropriate responses by the host defense system that may
damage healthy host tissues as badly as or worse than the invading agent. Direct injury by the
invading agent usually results from synthesis and secretion of microbial enzymes, proteins, toxic
lipids, and toxins that disrupt host cell membranes, metabolic machinery, and the extracellular
matrix that usually inhibits microbial migration.

Indirect injury is mediated by structural or secreted molecules, such as endotoxin, leukocidin, and
toxic shock syndrome toxin-1 (TSST-1), which may alter local vasomotor tone and integrity,
change the characteristics of the tissue perfusate, and generally interfere with the delivery of
oxygen and nutrients and removal of waste products from local tissues. [4, 5]

On a macroscopic level, the invading agents and the host defenses both tend to increase airway
smooth muscle tone and resistance, mucus secretion, and the presence of inflammatory cells and
debris in these secretions. These materials may further increase airway resistance and obstruct the
airways, partially or totally, causing airtrapping, atelectasis, and ventilatory dead space. In
addition, disruption of endothelial and alveolar epithelial integrity may allow surfactant to be
inactivated by proteinaceous exudate, a process that may be exacerbated further by the direct
effects of meconium or pathogenic microorganisms.

In the end, conducting airways offer much more resistance and may become obstructed, alveoli
may be atelectatic or hyperexpanded, alveolar perfusion may be markedly altered, and multiple
tissues and cell populations in the lung and elsewhere sustain injury that increases the basal
requirements for oxygen uptake and excretory gas removal at a time when the lungs are less able
to accomplish these tasks.

Alveolar diffusion barriers may increase, intrapulmonary shunts may worsen, and
ventilation/perfusion (V/Q) mismatch may further impair gas exchange despite endogenous
homeostatic attempts to improve matching by regional airway and vascular constriction or
dilatation. Because the myocardium has to work harder to overcome the alterations in pulmonary
vascular resistance that accompany the above changes of pneumonia, the lungs may be less able
to add oxygen and remove carbon dioxide from mixed venous blood for delivery to end organs.
The spread of infection or inflammatory response, either systemically or to other focal sites, further
exacerbates the situation.

Viral 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 (see Clinical Presentation). 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.

In bacterial infections, the alveoli fill with proteinaceous fluid, which triggers a brisk influx of red
blood cells (RBCs) and polymorphonuclear (PMN) cells (red hepatization) followed by the
deposition of fibrin and the degradation of inflammatory cells (gray hepatization). 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 (see Clinical Presentation).

Four stages of lobar pneumonia have been described. In the first stage, which occurs within 24
hours of infection, the lung is characterized microscopically by vascular congestion and alveolar
edema. Many bacteria and few neutrophils are present. The stage of red hepatization (2-3 d), so
called because of its similarity to the consistency of liver, is characterized by the presence of many
erythrocytes, neutrophils, desquamated epithelial cells, and fibrin within the alveoli. In the stage
of gray hepatization (2-3 d), the lung is gray-brown to yellow because of fibrinopurulent exudate,
disintegration of RBCs, and hemosiderin. The final stage of resolution is characterized by
resorption and restoration of the pulmonary architecture. Fibrinous inflammation may lead to
resolution or to organization and pleural adhesions.

Bronchopneumonia, a patchy consolidation involving one or more lobes, usually involves the
dependent lung zones, a pattern attributable to aspiration of oropharyngeal contents. The
neutrophilic exudate is centered in bronchi and bronchioles, with centrifugal spread to the adjacent
alveoli.

In interstitial pneumonia, patchy or diffuse inflammation involving the interstitium is characterized


by infiltration of lymphocytes and macrophages. The alveoli do not contain a significant exudate,
but protein-rich hyaline membranes similar to those found in adult respiratory distress syndrome
(ARDS) may line the alveolar spaces. Bacterial superinfection of viral pneumonia can also produce
a mixed pattern of interstitial and alveolar airspace inflammation.

Miliary pneumonia is a term applied to multiple, discrete lesions resulting from the spread of the
pathogen to the lungs via the bloodstream. The varying degrees of immunocompromise in miliary
tuberculosis (TB), histoplasmosis, and coccidioidomycosis may manifest as granulomas with
caseous necrosis to foci of necrosis. Miliary herpesvirus, cytomegalovirus (CMV), or varicella-
zoster virus infection in severely immunocompromised patients results in numerous acute
necrotizing hemorrhagic lesions.

Etiology
Pneumonia can be caused by a myriad of microorganisms. Clinical suspicion of a particular
offending agent is derived from clues obtained during the history and physical examination. While
virtually any microorganism can lead to pneumonia, specific bacterial, viral, fungal, and
mycobacterial infections are most common in previously healthy children. The age of infection,
exposure history, risk factors for unusual pathogens, and immunization history all provide clues to
the infecting agent.

In a prospective multicenter study of 154 hospitalized children with acute community-acquired


pneumonia (CAP) in whom a comprehensive search for an etiology was sought, a pathogen was
identified in 79% of children. Pyogenic bacteria accounted for 60% of cases, of which 73% were
due to Streptococcus pneumoniae, while the atypical bacteria Mycoplasma pneumoniae and
Chlamydophila pneumoniae were detected in 14% and 9%, respectively. Viruses were documented
in 45% of children. Notably, 23% of the children had concurrent acute viral and bacterial disease.
In the study, preschool-aged children had as many episodes of atypical bacterial lower respiratory
infections as older children. Multivariable analyses revealed that high temperature (38.4C) within
72 hours after admission and the presence of pleural effusion were significantly associated with
bacterial pneumonia. [6]

Specific etiologic agents vary based on age groups (ie, newborns, young infants, infants and
toddlers, 5-year-olds, school-aged children and young adolescents, older adolescents).

Newborns
In newborns (age 0-30 d), organisms responsible for infectious pneumonia typically mirror those
responsible for early onset neonatal sepsis. This is not surprising in view of the role that maternal
genitourinary and gastrointestinal tract flora play in both processes. Infections with group B
Streptococcus, Listeria monocytogenes, or gram-negative rods (eg, Escherichia coli, Klebsiella
pneumoniae) are common causes 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.

Group B Streptococcus (GBS) was the most common bacterial isolate in most locales from the late
1960s to the late 1990s, when the impact of intrapartum chemoprophylaxis in reducing neonatal
and maternal infection by this organism became evident. E coli has become the most common
bacterial isolate among VLBW infants (1500 g or less) since that time. [7] Other potential bacterial
organisms include the following:

Nontypeable Haemophilus influenzae (NTHi)


Other gram-negative bacilli
Enterococci
Staphylococcus aureus

Some organisms acquired perinatally may not cause illness until later in infancy, including
Chlamydia trachomatis, U urealyticum, Mycoplasma hominis, CMV, and Pneumocystis carinii. C
trachomatis organisms are presumably transmitted at birth during passage through an infected
birth canal, although most infants are asymptomatic during the first 24 hours and develop
pneumonia only after the first 2 weeks of life.

Group B streptococci infections are most often transmitted to the fetus in utero, usually as a result
of colonization of the mother's vagina and cervix by the organism. Agents of chronic congenital
infection, such as CMV, Treponema pallidum (the cause of pneumonia alba), Toxoplasma gondii,
and others, may cause pneumonia in the first 24 hours of life. The clinical presentation usually
involves other organ systems as well.

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 [Ig] G]) 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.

Newborns may also be affected by the bacteria and viruses that commonly cause infections in older
infants and children. Risk factors for infection include older siblings, group daycare, and lack of
immunization.

Young infants
In the young infant (aged 1-3 mo), continued concern about the perinatally acquired pathogens
mentioned above remains. However, most bacterial pneumonia in this age group is community
acquired and involves S pneumoniae, S aureus, and nontypeable H influenzae. S pneumoniae is by
far the most common bacterial pathogen in this age group. Infection with any of these pyogenic
bacteria may be complicated by lung abscess, parapneumonic effusions, and empyema, although
S aureus is notorious for such complications. [8]

At this age, infants are incompletely immunized and remain at higher risk for H influenzae type B
and pneumococcal disease, although herd immunity gained from widespread immunization of the
population has been broadly protective. It is important to note that the current conjugate
pneumococcal vaccine provides protection against 13 common pneumococcal types, but
nonvaccine types remain problematic.

Most lower respiratory tract disease in young infants occurs during the respiratory virus season
and is viral in origin, particularly in the patient with clinical bronchiolitis. The most common viral
agents include RSV, parainfluenza viruses, influenza virus, adenovirus, and human
metapneumovirus (hMPV).

Atypical organisms may rarely cause infection in infants. Of these, C trachomatis, U urealyticum,
CMV, and P carinii are described.

Bordetella pertussis infection leads to pneumonia in as many as 20% of infected infants (as a
complication of the whooping cough infection).

Among other potential atypical bacterial pathogens, U urealyticum and U parvum have been
recovered from endotracheal aspirates shortly after birth in very low birth weight (VLBW) infants
and have been variably associated with various adverse pulmonary outcomes, including
bronchopulmonary dysplasia (BPD). [9, 10, 11, 12] Whether these organisms are causal or simply a
marker of increased risk is unclear.

Infants, toddlers, and preschool-aged children

Viruses remain the most common cause of pneumonia in this age group, accounting for
approximately 90% of all lower respiratory tract infections. Tsolia et al identified a viral infection
among 65% of hospitalized children with community-acquired pneumonia. [13]

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. Parainfluenza type 3 infection occurs
in the spring, and types 1 and 2 occur in the fall. Influenza occurs in the winter.

Other viruses that cause pneumonia less frequently in infants and young children include
adenovirus, enterovirus, rhinovirus, and coronavirus. A recent addition to this list is hMPV, which
causes an illness similar to RSV and may be responsible for one third to one half of non-RSV
bronchiolitis. The herpesviruses (HSV, VZV, and CMV) may rarely cause pneumonia, particularly
in children with impaired immune systems.
Bacterial infections in this age group are seen on a regular basis. S pneumoniae is by far the most
common bacterial cause of pneumonia. Among hospitalized children with bacterial pneumonia, S
pneumoniae accounts for 21-44% of disease. [6, 14, 15] Other agents to consider include H influenzae
type B (HiB) (very uncommon in immunized children [16] ), S pyogenes, and S aureus.

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. Evidence suggests that breastfeeding has a protective effect against invasive pneumococcal
infection.

School-aged children and young adolescents

M pneumoniae is the most frequent cause of pneumonia among older children and adolescents.
Mycoplasma accounts for 14-35% of pneumonia hospitalizations in this age group. [6, 13, 17]
Children in homeless shelters and group homes and those with household contacts are at particular
risk. Similarly, the diagnosis must be considered in immunocompromised children.

In this age group, pyogenic bacterial pneumonia remains a concern, usually caused by S
pneumoniae. Other pyogenic bacterial pathogens to consider include S aureus and S pyogenes.

Chlamydophila pneumoniae also causes pneumonia. The related organism, C psittaci, is an


unusual cause of pneumonia that occurs in people who work with and handle birds.

In immunosuppressed individuals, opportunistic infections with organisms such as Aspergillus


species, Pneumocystis jirovecii, and CMV can occur.

Viral pneumonia remains common in this age group. Influenza pneumonia is a particular concern
because ongoing infection with this virus predisposes to the development of bacterial
superinfection, usually with S pneumoniae or S aureus.

Older adolescents

M pneumoniae is the most common cause of community-acquired pneumonia during the teenage
and young adult years. Atypical pneumonia caused by C pneumoniae can present with identical
signs and symptoms. Bacterial pneumonia caused by S pneumoniae is also seen.

Pulmonary infections caused by dimorphic fungi are also seen in this age group. Histoplasma
capsulatum, which is found in nitrate-rich soil, is usually acquired as a result of inhalation of
spores. Chicken coops and other bird roosts and decaying wood are often-cited sources.
Cryptococcus neoformans is a common infection among pigeon breeders, but it is unusual in other
immunocompetent individuals.

Blastomyces dermatitides, another dimorphic fungus, is found in certain geographic locations,


most notably the Ohio and Mississippi River valleys. As with histoplasmosis, blastomycosis is
acquired by inhalation of spores. Although 3 distinct forms of infection exist, the most common is
acute pneumonia, which, in previously healthy individuals, most often resolves without treatment.
Viral pneumonias are common in this age group are usually mild and self-limited, but influenza
pneumonia can be severe or protracted, particularly when a bacterial infection follows.

TB pneumonia in children warrants special mention. It can occur in any age group, and it is
important to remember that children with TB usually do not present with symptoms until 1-6
months after primary infection. Any child with pneumonia who has a history of TB exposure, or
who has traveled to a TB-endemic area of the world needs to be fully evaluated for the possibility
of tuberculosis.

Legionella pneumophila, the agent of Legionnaires disease, can also cause pneumonia, although
it is uncommon in the pediatric age group.

Not all pneumonia is caused by infectious agents. Children who have severe gastroesophageal
reflux (GERD) may develop chemical pneumonitis secondary to recurrent aspiration. Inhalation
of certain chemicals or smoke may cause pulmonary inflammation. Additionally, aspiration
pneumonia is more common in children with neurologic impairment, swallowing abnormalities,
gastrointestinal motility, or a gastrostomy tube. Oral anaerobic flora, with or without aerobes, is
the most common etiologic agent.

A study by Thomson et al compared hospital management and outcomes of children with


neurologic impairment diagnosed with aspiration versus nonaspiration pneumonia. The study
found that hospitalized children with neurologic impairment diagnosed with aspiration pneumonia
had significantly longer length of stay; more ICU transfers; greater hospitalization costs; and more
30-day readmissions than children with neurologic impairment diagnosed with nonaspiration
pneumonia. [18]

Immunocompromised children

Some children who are immunocompromised, whether secondary to HIV infection/AIDS, an


immune disorder, or chemotherapy for a malignancy, are at risk for pneumonias with opportunistic
agents. Virtually any bacteria, virus, fungus, or even parasite can invade and infect the lungs if the
immune system is sufficiently impaired. Carefully obtained samples for appropriate microbiologic
testing are paramount in such patients so that therapy can be optimized.

Children with cystic fibrosis are especially prone to develop infections with S aureus,
Pseudomonas aeruginosa, Burkholderia cepacia, and other multidrug-resistant organisms.

P jirovecii pneumonia (PCP) is common in the most severely compromised children and can lead
to respiratory failure and death in those who are profoundly immunocompromised. Adenovirus
infections can be severe in these children as well, leading to bronchiolitis obliterans or hyperlucent
lung syndrome. In addition, CMV poses a great risk to immunocompromised patients.

Fungal pneumonia, caused by Aspergillus, Zygomycetes, or other related fungi, occur in


immunocompromised patients who undergo prolonged hospitalization, have prolonged
neutropenia, and/or have received broad-spectrum antibiotics. Patients with underlying
hematologic malignancies are at the highest risk.
Patients with sickle cell disease have problems with their complement system as well as functional
asplenia, which predisposes them to infection with encapsulated organisms such as S pneumoniae
and H influenzae type B. M pneumoniae is also a common agent of pneumonia is this group of
patients.

Epidemiology
United States statistics

Pneumonia can occur at any age, although it is more common in younger children. 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. [19]

Thompson et al reported that, after elderly persons, the second highest rates of influenza-associated
hospitalizations in the United States were in children younger than 5 years. [20] The investigators
evaluated annual influenza-associated hospitalizations by hospital discharge category, discharge
type, and age group.

In a randomized double-blind trial, the heptavalent pneumococcal vaccine reduced the incidence
of clinically diagnosed and radiographically diagnosed pneumonia among children younger than
5 years by 4% and 20%, respectively. [21] Although the overall rate of pneumonia has decreased in
the United States with the use of the 7-valent vaccine, the rate of empyema and complicated
pneumonia has increased. [22] With the use of the 13-valent conjugated pneumococcal
polysaccharide vaccine, the overall rates of pneumonia are anticipated to drop further. The new
vaccine includes serotypes that have become associated with complicated or antibiotic-resistant
disease (19A and 6A, for example).

In school-aged children and adolescents, bronchopneumonia occurs in 0.8-2% of all pertussis cases
and 16-20% of hospitalized cases. M pneumoniae accounts for 14-35% of pneumonia
hospitalizations in this age group, [6, 13, 17] and mycobacterial pneumonia has recently been noted
with increasing frequency in some inner-city areas, particularly children in homeless shelters and
group homes and those with household contacts.

International statistics

Pneumonia and other lower respiratory tract infections are the leading cause of death worldwide.
The WHO Child Health Epidemiology Reference Group estimated the median global incidence of
clinical pneumonia to be 0.28 episodes per child-year. [23] This equates to an annual incidence of
150.7 million new cases, of which 11-20 million (7-13%) are severe enough to require hospital
admission. Ninety-five percent of all episodes of clinical pneumonia in young children worldwide
occur in developing countries.

Approximately 150 million new cases of pneumonia occur annually among children younger than
5 years worldwide, accounting for approximately 10-20 million hospitalizations. [19] A WHO Child
Health Epidemiology Reference Group publication cited the incidence of community-acquired
pneumonia among children younger than 5 years in developed countries as approximately 0.026
episodes per child-year, [23] and a study conducted in the United Kingdom showed that 59% of
deaths from pertussis are associated with pneumonia.

Prognosis
Overall, the prognosis is good. Most cases of viral pneumonia resolve without treatment; common
bacterial pathogens and atypical organisms respond to antimicrobial therapy (see Treatment and
Management). Long-term alteration of pulmonary function is rare, even in children with
pneumonia that has been complicated by empyema or lung abscess.

Patients placed on a protocol-driven pneumonia clinical pathway are more likely to have favorable
outcomes. The prognosis for varicella pneumonia is somewhat more guarded. Staphylococcal
pneumonia, although rare, can be very serious despite treatment.

Morbidity

Although viral pneumonias are common in school-aged children and adolescents and are usually
mild and self-limited, these 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.

Morbidity and mortality from RSV and other viral infections is higher among premature infants
and infants with underlying lung disease. Significant sequelae occur with adenoviral disease,
including bronchiolitis obliterans and necrotizing bronchiolitis. With neonatal pneumonia, even if
the infection is eradicated, many hosts develop long-lasting or permanent pulmonary changes that
affect lung function, the quality of life, and susceptibility to later infections.

Infants and postpubertal adolescents with TB pneumonia are at increased risk of disease
progression. If TB is not treated during the early stages of infection, approximately 25% of children
younger than 15 years develop extrapulmonary disease.

Bronchopneumonia occurs in 0.8-2% of all pertussis cases and 16-20% of hospitalized cases; the
survival rate of these patients is much lower than in those with pneumonia that is attributed to other
causes.

Immunocompromised children, those with underlying lung disease, and neonates are at high risk
for severe sequelae, and they are also susceptible to various comorbidities. Cryptococcosis may
occur in as many as 5-10% of patients with AIDS, and acute chest syndrome occurs in 15-43% of
patients with sickle cell disease. Individuals with sickle cell disease not only have problems with
their complement system, but they also have functional asplenia, which predisposes them to
infection with encapsulated organisms such as S pneumoniae and H influenzae type B.

Mortality
The United Nations Children's Fund (UNICEF) estimates that 3 million children die worldwide
from pneumonia each year; these deaths almost exclusively occur in children with underlying
conditions, such as chronic lung disease of prematurity, congenital heart disease, and
immunosuppression. Although most fatalities occur in developing countries, pneumonia remains
a significant cause of morbidity in industrialized nations.

According to the WHOs Global Burden of Disease 2000 Project, lower respiratory infections were
the second leading cause of death in children younger than 5 years (about 2.1 million [19.6%]). [23]
Most children are treated as outpatients and fully recover. However, in young infants and
immunocompromised individuals, mortality is much higher. In studies of adults with pneumonia,
a higher mortality rate is associated with abnormal vital signs, immunodeficiency, and certain
pathogens.

Patient Education
Counsel parents regarding the need to prevent exposure of infants to tobacco smoke, and, as part
of anticipatory primary care, educate parents regarding later infectious exposures in daycare
centers, schools, and similar settings as well as the importance of hand washing. In addition,
discuss the benefit infants may receive from pneumococcal immunization and annual influenza
immunization and the potential benefits and costs of RSV immune globulin (see Prevention).
Emphasize careful longitudinal surveillance for long-term problems with growth, development,
otitis, reactive airway disease, and other complications.

Most children treated with outpatient antibiotics are much improved within 48 hours after the
initiation of treatment. Educate parents about and caution them to look for the signs of increasing
respiratory distress and to seek medical attention immediately should any of these signs appear.

For patient education resources, see the Lung Disease and Respiratory Health Center. Also, see
the patient education articles Bronchoscopy, Viral Pneumonia, and Bacterial Pneumonia.

History
Newborns with pneumonia rarely cough; they more commonly present with poor feeding and
irritability, as well as tachypnea, retractions, grunting, and hypoxemia. Grunting in a newborn
suggests a lower respiratory tract disease and is due to vocal cord approximation as they try to
provide increased positive end-expiratory pressure (PEEP) and keep their lower airways open.

After the first month of life, cough is the most common presenting symptom of pneumonia. Infants
may have a history of antecedent upper respiratory symptoms. Grunting may be less common in
older infants; however, tachypnea, retractions, and hypoxemia are common and may be
accompanied by a persistent cough, congestion, fever, irritability, and decreased feeding. Any
maternal history of Chlamydia trachomatis infection should be determined.

Infants with bacterial pneumonia are often febrile, but those with viral pneumonia or pneumonia
caused by atypical organisms may have a low-grade fever or may be afebrile. The child's caretakers
may complain that the child is wheezing or has noisy breathing. Toddlers and preschoolers most
often present with fever, cough (productive or nonproductive), tachypnea, and congestion. They
may have some vomiting, particularly posttussive emesis. A history of antecedent upper
respiratory tract illness is common.

Older children and adolescents may also present with fever, cough (productive or nonproductive),
congestion, chest pain, dehydration, and lethargy. In addition to the symptoms reported in younger
children, adolescents may have other constitutional symptoms, such as headache, pleuritic chest
pain, and vague abdominal pain. Vomiting, diarrhea, pharyngitis, and otalgia/otitis are other
common symptoms.

Travel history is important because it may reveal an exposure risk to a pathogen more common to
a specific geographic area (eg, dimorphic fungi). Any exposure to TB should always be
determined. In addition, exposure to birds (psittacosis), bird droppings (histoplasmosis), bats
(histoplasmosis), or other animals (zoonoses, including Q fever, tularemia, and plague) should be
determined.

In children with evidence for recurrent sinopulmonary infections, a careful history to determine
the underlying cause is needed. The recurrent nature of the infections may be unveiling an innate
or acquired immune deficiency, an anatomic defect, or another genetic disease (cystic fibrosis,
ciliary dyskinesia).

Tuberculosis

A history of TB exposure to possible sources should be obtained in every patient who presents
with signs and symptoms of pneumonia (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). Children with TB usually do not present with symptoms until 1-6 months after primary
infection. These may include fever, night sweats, chills, cough (which may include hemoptysis),
and weight loss.

Physical Examination
The signs and symptoms of pneumonia are often nonspecific and widely vary based on the
patients age and the infectious organisms involved. Tachypnea is the most sensitive finding in
patients with diagnosed pneumonia.

Initial evaluation

Early in the physical examination, identifying and treating respiratory distress, hypoxemia, and
hypercarbia is important. Visual inspection of the degree of respiratory effort and accessory muscle
use should be performed to assess for the presence and severity of respiratory distress. The
examiner should simply observe the patient's respiratory effort and count the respirations for a full
minute. In infants, observation should include an attempt at feeding, unless the baby has extreme
tachypnea.
Pulmonary findings in all age groups may include accessory respiratory muscle recruitment, such
as nasal flaring and retractions at subcostal, intercostal, or suprasternal sites. Signs such as
grunting, flaring, severe tachypnea, and retractions should prompt the clinician to provide
immediate respiratory support. Retractions result from the effort to increase intrathoracic pressure
to compensate for decreased compliance.

An emergency department (ED)-based study conducted in the United States found that respiratory
rate alone and subjective clinical impression of tachypnea did not discriminate children with and
without radiographic pneumonia. [24] The WHO clinical criteria for pneumonia has also been
reported to demonstrate poor sensitivity (34.3%) in diagnosing radiographic pneumonia in children
presenting to a pediatric ED. [25] However, children with tachypnea as defined by WHO respiratory
rate thresholds were more likely to have pneumonia than children without tachypnea. The WHO
thresholds are as follows:

Children younger than 2 months - Greater than or equal to 60 breaths/min


Children aged 2-11 months - Greater than or equal to 50 breaths/min
Children aged 12-59 month - Greater than or equal to 40 breaths/min

Airway secretions may vary substantially in quality and quantity but are most often profuse and
progress from serosanguineous to a more purulent appearance. White, yellow, green, or
hemorrhagic colors and creamy or chunky textures are not infrequent. If aspiration of meconium,
blood, or other proinflammatory fluid is suspected, other colors and textures reflective of the
aspirated material may be seen.

Infants may have external staining or discoloration of skin, hair, and nails with meconium, blood,
or other materials when they are present in the amniotic fluid. The oral, nasal, and, especially,
tracheal presence of such substances is particularly suggestive of aspiration.

An assessment of oxygen saturation by pulse oximetry should be performed early in the evaluation
of all children with respiratory symptoms. Cyanosis may be present in severe cases. When
appropriate and available, capnography may be useful in the evaluation of children with potential
respiratory compromise.

Cyanosis of central tissues, such as the trunk, implies a deoxyhemoglobin concentration of


approximately 5 g/dL or more and is consistent with severe derangement of gas exchange from
severe pulmonary dysfunction as in pneumonia, although congenital structural heart disease,
hemoglobinopathy, polycythemia, and pulmonary hypertension (with or without other associated
parenchymal lung disease) must be considered.

Chest pain may be observed with inflammation of or near the pleura. Abdominal pain or tenderness
is often seen in children with lower lobe pneumonia. The presence and degree of fever depends on
the organism involved, but high temperature (38.4C) within 72 hours after admission and the
presence of pleural effusion have been reported to be significantly associated with bacterial
pneumonia. [6]
Pneumonia may occur as a part of another generalized process. Therefore, signs and symptoms
suggestive of other disease processes, such as rashes and pharyngitis, should be sought during the
examination.

Auscultation

Auscultation is perhaps the most important portion of the examination of the child with respiratory
symptoms. The examination is often very difficult in infants and young children for several
reasons. Babies and young children often cry during the physical examination making auscultation
difficult. The best chance of success lies in prewarming hands and instruments and in using a
pacifier to quiet the infant. The opportunity to listen to a sleeping infant should never be lost.

Older infants and toddlers may cry because they are ill or uncomfortable, but, most often, they
have stranger anxiety. For these children, it is best to spend a few minutes with the parents in the
child's presence. If the child sees that the parent trusts the examining physician then he or she may
be more willing to let the examiner approach. A small toy may help to gain the child's trust. Any
part of the examination using instruments should be deferred as long as possible, because the child
may find the medical equipment frightening. Occasionally, if the child is allowed to hold the
stethoscope for a few minutes, it becomes less frightening. Even under the best of circumstances,
examining a toddler is difficult. If the child is asleep when the physician begins the evaluation,
auscultation should be performed early.

Children with respiratory symptoms may have a concomitant upper respiratory infection with
copious upper airway secretions. This creates another potential problem, the transmission of upper
airway sounds. In many cases, the sounds created by upper airway secretions can almost obscure
true breath sounds and lead to erroneous diagnoses. If the etiology of sounds heard through the
stethoscope is unclear, the examiner should listen to the lung fields and then hold the stethoscope
near the child's nose. If the sounds from both locations are approximately the same, the likely
source of the abnormal breath sounds is the upper airway.

Even when the infant or young child is quiet and has a clear upper airway, the child's normal
physiology may make the examination difficult. The minute ventilation is the product of the
respiratory rate and tidal volume. In young children, respiratory rate makes a very large
contribution to the overall minute ventilation. In other words, babies take many shallow breaths as
opposed to a few deep ones. Therefore, a subtle finding, particularly one at the pulmonary bases,
can be missed.

The sine qua non for pneumonia has always been the presence of crackles or rales. Although often
present, focal crackles as a stand-alone physical examination finding is neither sensitive nor
specific for the diagnosis of pneumonia. [26, 27, 28] Additionally, not all children with pneumonia
have crackles.

Rales, rhonchi, and cough are all observed much less frequently in infants with pneumonia than in
older individuals. If present, they may be caused by noninflammatory processes, such as
congestive heart failure, condensation from humidified gas administered during mechanical
ventilation, or endotracheal tube displacement. Although alternative explanations are possible,
these findings should prompt careful consideration of pneumonia in the differential diagnosis.

Other examination findings suggestive of pneumonia include asymmetry of breath sounds in


infants, such as focal wheezing or decreased breath sounds in one lung field, and asymmetry of
chest excursions, which suggest air leak or emphysematous changes secondary to partial airway
obstruction. Similarly, certain more diffuse lung infections (eg, viral infections) may result in
generalized crackles or wheezing.

In lobar pneumonia, fibrinous inflammation may extend into the pleural space, causing a rub heard
by auscultation. Pericardial effusion in patients with lower lobe pneumonia due to H influenzae
may also cause a rub. Other signs and/or findings in lobar pneumonia include abdominal pain or
an ileus accompanied by emesis in patients with lower lobe pneumonia and nuchal rigidity in
patients with right upper lobe pneumonia.

Percussion may reveal important information. Occasionally, a child presents with a high fever and
cough but without ausculatory findings suggestive of pneumonia. In such cases, percussion may
help to identify an area of consolidation.

Systemic and localized findings

Systemic findings in newborns with pneumonia may provide clues to the etiology. Rash or
jaundice at birth may indicate congenital infection. Nonspecific findings such as tachycardia,
glucose intolerance, abdominal distention, hypoperfusion, and oliguria are very common is
moderately to severely ill newborns, and are not specific for a lung focus of infection. Localized
findings include conjunctivitis (consider C trachomatis), vesicles or other focal skin lesions
(consider HSV), and unusual nasal secretions (consider congenital syphilis).

Adenopathy in older children suggests long-standing infection and should suggest a more chronic
cause such as TB or a dimorphic fungal infection (eg, histoplasmosis, blastomycosis).
Hepatomegaly from infection may result from the presence of some chronic causative agents,
cardiac impairment, or increased intravascular volume. Apparent hepatomegaly may result if
therapeutic airway pressures allow generous lung inflation and downward displacement of a
healthy liver.

Other considerations

Infants infected with organisms in utero or via the maternal genital tract commonly present within
the first few hours after birth, but if infection is acquired during the delivery, the presentation may
be delayed. The usual presenting symptoms include tachypnea, hypoxemia, and signs of
respiratory distress. Auscultation may reveal diffuse fine crackles.

Early onset group B streptococci infection usually presents via ascending perinatal infection as
sepsis or pneumonia within the first 24 hours of life. C trachomatis pneumonia should be
considered in infants aged 2-4 weeks and is often associated with conjunctivitis. Infants infected
with C pneumoniae,U urealyticum,Mycoplasma hominis, CMV, and P carinii present between age
4 and 11 weeks with an afebrile pneumonia characterized by a staccato cough, tachypnea, and,
occasionally, hypoxia.

Infants or toddlers with bacterial pneumonia may present with lethargy, irritability, acidosis,
hypotonia, or hypoxia that is out of proportion to ausculatory findings; school-aged children and
adolescents are often febrile and appear ill. Mycoplasma infections are indolent, with gradual onset
of malaise, low-grade fever, headache, and cough. C pneumoniae is also fairly common in children
aged 5 years and presents in a similar fashion.

Pneumonia caused by B pertussis occurs predominantly in infants who have not completed their
vaccinations or in children who did not receive vaccinations. Their clinical presentation includes
coryza, malaise, fever, paroxysms of cough occasionally accompanied by emesis, apnea, poor
feeding, and cyanosis. Older adolescents infected with pertussis present with a paroxysmal cough,
which persists for more than 3 weeks and may last up to 3 months, unlike the whooping cough of
younger children. Chest radiographs in this group of patients are almost always normal, despite
the intensity of the cough illness.

Although infection with H capsulatum is usually asymptomatic in older children and adolescents,
infants and young children are at risk for symptomatic infection, which may cause respiratory
distress and hypoxemia.

Pneumonia is the most common cause of acute chest syndrome, which occurs in 15-43% of patients
with sickle cell disease. This syndrome is characterized by fever, chest pain, dyspnea, cough,
tachypnea, crackles.

To see complete information on Afebrile Pneumonia Syndrome, please go to the main article by
clicking here.

Patients With Recurrent Pneumonias


Occasionally, a patient has pneumonia that continues to manifest clinically (persistent or
unresponsive pneumonia) , radiographically (eg, 8 wk after antibiotic treatment), or both despite
adequate medical management. Studies have documented that the usual pathogens (eg,
pneumococcus, non-typeable H influenza, Moraxella catarrhalis) are causative agents.

Other patients may present with a history of recurrent pneumonias, defined as more than 1 episode
per year or more than 3 episodes in a lifetime and again the organisms responsible are the common
pathogens.

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 radiographic findings with and without
symptoms. This method places these children in 1 of 3 categories (see the Table below) that help
to narrow the differential diagnoses.
A careful history and examination are helpful to further narrow the differential diagnosis (see
Differential Diagnosis). However, more testing is often needed to confirm most of these diagnoses
and is generally outside the scope of a primary care provider.

Diagnostic Considerations
Pneumonia can occur at any age, although it is more common in younger children. Different age
groups tend to be infected by different pathogens, which affects diagnostic and therapeutic
decisions.

Many patients referred for evaluation 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. 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.

Approach Considerations
Diagnostic tests for pneumonia may include the following:

Pulse oximetry
Complete blood cell (CBC) count
Sputum and blood cultures
Serology
Chest radiography
Ultrasonography

Data show that point-of-care ultrasonography accurately diagnoses most cases of pneumonia in
children and young adults. In a study of 200 babies, children, and young adults (21 years),
ultrasonography had an overall sensitivity of 86% and a specificity of 89% for diagnosing
pneumonia. Ultrasonography may eventually come to replace x-rays for diagnosis [1, 2, 29]

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 as various
organisms cause pneumonia. Bacterial (including mycoplasmal, chlamydial, and acid fast), viral,
and fungal infections are relatively common and have similar presentations, complicating clinical
diagnosis. Furthermore, basic laboratory testing and radiologic testing are often not helpful in
determining the etiology of pneumonia, and the treatments widely vary.

In patients with complicated pneumonia who have not had a treatment response or who require
hospital admission, several diagnostic studies aimed at identifying the infectious culprit are
warranted, including cultures, serology, a CBC count with the differential, and acute-phase
reactant levels (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]).
Numerous factors may interfere with the ability to grow a likely pathogen in the microbiology
laboratory, including (but not limited to) the following: pretreatment with antibiotics that limit in
vitro but not in vivo growth, sputum contaminants that overgrow the pathogen, and pathogens
that do not replicate in currently available culture systems. Techniques that may help overcome
some of these limitations include antigen detection, nucleic acid probes, polymerase chain
reaction (PCR)-based assays, or serologic tests.

Although once widely used, tests such as latex agglutination for detection of group B
streptococcal antigen in urine, serum, or other fluids have fallen into disfavor because of poor
predictive value; however, new generations of nonculture-based technologies continue to
undergo development and may be more accurate and widely available in the future.

Complete Blood Cell Count


Laboratory testing of children with a clinical diagnosis of pneumonia is not typically necessary
in the outpatient setting, since criteria for admission would generally depend on clinical
appearance or vital signs. For hospitalized patients, laboratory testing can be helpful to document
and trend improvement or worsening over time.

Testing should include a CBC count with differential and evaluation of acute-phase reactants
(ESR, CRP, or both) and sedimentation rate. The total white blood cell (WBC) count and
differential may aid in determining if an infection is bacterial or viral, and, together with clinical
symptoms, chest radiography, and ESR can be useful in monitoring the course of pneumonia. In
cases of pneumococcal pneumonia, the WBC count is often elevated.

Before widespread pneumococcal immunization, Bachur et al observed that approximately 25%


of febrile children with a WBC count of more than 20,000/L, but without lower respiratory tract
findings on examination, had radiographic pneumonia (termed occult pneumonia). [30] Although
blood testing was obtained less frequently in the post-Prevnar era, recent studies by the same
group demonstrated that leukocytosis was still associated with occult pneumonia. [31, 32]

Sputum Gram Stain and Culture


Sputum is rarely produced in children younger than 10 years, and samples are always
contaminated by oral flora. In the cooperative older child with a productive cough, a sputum
Gram stain may be obtained (see the image below); however, very few children are able to
cooperate with such a test. An adequate sputum culture should contain more than 25 PMN cells
per field and fewer than 10 squamous cells per field.
(Left) Gram stain demonstrating
gram-positive cocci in pairs and chains and (right) culture positive for Streptococcus
pneumoniae.
View Media Gallery

In situations in which a microbiologic diagnosis is essential, endotracheal cultures and/or


bronchoalveolar lavage culture can be sent for the isolation of offending pathogens. This is most
important in patients with enigmatic and/or severe pneumonia, and it should be considered a
priority in patients with compromised immune systems. Routine cultures for respiratory
pathogens should be requested, along with special stains for PCP and special stains and cultures
for Legionella, fungi, and acid-fast organisms. Viral cultures are also routinely requested.

Blood Culture
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. In a study of 168 patients with known pneumonia, Wubbel et al
found only sterile blood cultures. [33]

In general, blood culture results are positive in less than 5% of patients with pneumococcal
pneumonia. The percentage is even less in patients with Staphylococcus infection. However, a
blood culture is still recommended in complicated cases of pneumonia. It may be the only way to
identify the pathogen and its antimicrobial susceptibility patterns.

In neonates, blood culture with at least 1 mL of blood from an appropriately cleaned and
prepared peripheral venous or arterial site is essential, because many neonatal pneumonias are
hematogenous in origin and others serve as a focus for secondary seeding of the bloodstream.
Older patients should have larger-volume blood culture samples obtained based on their age and
the ease with which blood can be obtained. Blood culture samples obtained through freshly
placed indwelling vascular catheters may be helpful, but they generally are discouraged because
of the possibility of contamination with skin flora. Multiple cultures of blood from different sites
and/or those drawn at different times may increase the culture yield.

Guidelines published in 2011 and widely adopted across the USA [34] recommended obtaining
blood cultures on hospitalized patients with moderate to severe pneumonia, but subsequent
research has called into question the utility of a universal approach to obtaining a culture, in
favor of being more targeted [35] . There is rarely a significant change to management or length of
hospital stay even in the presence of a documented bacteremia, and the false-positive
(contaminant) rate of blood cultures may approach that of true bacteremia if low-risk patients are
included. As such, half of all blood cultures will be false-positive, and most of the true positives
won't impact patient care.

Serology
Because of the relatively low yield of cultures, more efforts are under way to develop quick and
accurate serologic tests for common lung pathogens, such as M pneumoniae, Chlamydophila
species, and Legionella.

In a Finnish study, of 278 patients diagnosed with community-acquired pneumonia, a total of 24


(9%) confirmed diagnoses of Mycoplasma infection were made, all of which had positive results
with IgM-capture test with convalescent-phase serum. [36] Acute and convalescent serum samples
were collected and tested using enzyme immunoassay for M pneumoniae 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. 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. [36]

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. [36] IgM serology is much more sensitive than cold
agglutinin assessments, which are more commonly used to aid in the diagnosis of Mycoplasma
infection and which demonstrate positive results in only 50% of cases.

Chlamydophila and Legionella species can be grown by experienced microbiologists; however,


serologic testing is also routinely performed to support or establish the diagnosis. Similarly, lung
infections caused by dimorphic fungi (eg, histoplasmosis) are more commonly diagnosed
serologically.

Inflammatory Markers
The use of markers of inflammation to support a diagnosis of suspected infection, including
pneumonia, remains controversial because results are nonspecific. Various indices derived from
differential leukocyte counts have been used most widely for this purpose, although
noninfectious causes of such abnormal results are numerous. Many reports have been published
regarding infants with proven infection who initially had neutrophil indices within reference
ranges.

Quantitative measurements of CRP, procalcitonin, cytokines (eg, interleukin [IL]-6), inter-alpha


inhibitor proteins (IaIp), [37] and batteries of acute-phase reactants have been touted to be more
specific but are limited by suboptimal positive predictive value.
Lag time from infection to abnormal values are noted for inflammatory markers; thus, serial
measurements are often necessary and do offer a high negative predictive value. However,
although these tests may be useful in assessing the resolution of an inflammatory process,
including infection, they are not sufficiently precise to establish a diagnosis without additional
supporting information. Decisions about antimicrobial therapy should not be based on
inflammatory markers alone.

Polymerase Chain Reaction


Relatively rapid testing (1-2 d) of viral infections through multiplex PCR is available in many
hospitals. PCR is more sensitive than antigen assays, and for some viruses (eg, hMPV), this
study may be the only test available. PCR also shows promise of being useful in diagnosing
streptococcal pneumonia. In one series of 63 children with empyema, a pathogen could be
detected in 53 (84%) by PCR compared to only 24 (35%) by culture of blood and/or pleural
fluid. The most frequently detected pathogen was pneumococcus, found in 45 patients. [38]

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.

PCR testing for TB is also widely available and is helpful in early identification of TB from
other mycobacteria in acid-fast cultures.

Skin Testing
These tests are used in diagnosing TB. Mantoux skin test (intradermal [ID] inoculation of 5
tuberculin units [TU] of purified protein derivative [PPD]) results should be read 48-72 hours
after placement.

Even if the child has received the BCG vaccine, Mantoux test results should be interpreted using
the criteria outlined as follows. 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. Chest radiography helps to confirm the diagnosis of a child with
positive Mantoux test results (see Chest Radiography).

Gastric Aspirates
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.

Cold Agglutinin Testing


In the young child or school-aged child with pneumonia, particularly the patient with a gradual
onset of symptoms and a prodrome consisting of headache and abdominal symptoms, a bedside
cold agglutinins test may help confirm the clinical suspicion of mycoplasmal infection.

This test is easily performed by placing a small amount of blood in a specimen tube containing
anticoagulant and inserting this into a cup filled with ice water. After a few minutes in the cold
water, the tube is held up to the light, tilted slightly, and slowly rotated. Small clumps of RBCs
coating the tube are indicative of a positive test result. Unfortunately, this test is positive in only
half the cases of mycoplasmal infection, and it is not very specific.

Urine Latex Agglutination Testing


Although antigen detection assays for S pneumoniae lack a high specificity in children, Neuman
and Harper observed that 76% of febrile children with a lobar infiltrate on chest radiograph had a
positive rapid urine antigen assay. [39]

Direct Antigen Detection


Although antiviral therapies are not often used, performing a nasal wash or nasopharyngeal swab
for RSV and influenza enzyme-linked immunoassay (ELISA) and viral culture can help to
establish a rapid diagnosis, which may be helpful in excluding other causes. Viral cultures can be
obtained in 1-2 days using newer cell culture techniques and may permit discontinuation of
unnecessary antibiotics. 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.

Chest Radiography
Chest radiography is indicated primarily in children with complications such as pleural effusions
and in those in whom antibiotic treatment fails to elicit a response. Computed tomography (CT)
scanning of the chest and ultrasonography are indicated in children with complications such as
pleural effusions and in those in whom antibiotic treatment fails to elicit a response. For more
information, see Imaging in Pediatric Pneumonia.

Bronchoscopy
Flexible fiberoptic bronchoscopy is occasionally useful to obtain lower airway secretions for
culture or cytology. 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.

The technique of direct rigid bronchoscopy may be used in larger infants; fiberoptic technique is
occasionally possible in smaller infants or infants in whom the site is not easily reached using the
rigid technique. Both this technique and protected brush tracheal aspirate sampling may not be
well tolerated in infants with significant lung disease and poor gas exchange who are very
dependent on continuous positive pressure ventilation.

Careful consideration of the diagnostic possibilities is necessary to send the samples for the
appropriate tests. Contamination of the bronchoscopic aspirate with upper airway secretions is
common; quantitative cultures can help distinguish contamination from infection. Culture and
Gram stain of an endotracheal aspirate obtained by aseptic technique as soon as possible after
intubation may be useful.

Under typical circumstances, airway commensals take as long as 8 hours to migrate down the
trachea. At least one study demonstrated that culture of endotracheal aspirates obtained within 8
hours of birth correlates very well with blood culture results and probably reflects aspirated
infected fluid. [40] The longer the tube has been in place, the greater the likelihood that recovered
organisms represent colonizing organisms rather than invasive pathogens; nonetheless, recovery
of a single recognized pathogen in large quantities may be helpful in the selection of antibiotic
therapy, especially if culture results from normally sterile sites are negative.

The absence of significant inflammatory cells in an endotracheal aspirate or other respiratory


specimen suggests that organisms recovered from that site are unlikely to be truly invasive
(unless the infant is markedly leukopenic). Thus, the organism represents colonization of the
respiratory tract and not infection.

Bronchoscopic Alveolar Lavage


Quantitative culture techniques, such as bronchoscopic alveolar lavage have been assessed in
non-neonatal populations and reportedly offer a specificity of more than 80%, depending on the
threshold selected (values from >100-100,000 colony-forming units [CFU]/mL have been used).
[41, 42]
Data from studies of neonates with suspected congenital pneumonia are lacking.

Protected Brush Tracheal Aspirate Sampling


Sites distant from the larger bronchi often cannot be sampled. Specimens may have an increased
risk of contamination with oral or airway commensals compared with bronchoscopic sampling
but are thought to be more accurate than a conventional endotracheal aspirate.

Nondirected specimens have been obtained through endotracheal tubes 3 mm or greater in


internal diameter and intuitively appear to offer decreased probability of contamination. Data
from neonates are sparse. [43] Unlike bronchoscopically obtained specimens, ensuring sampling
from a particular involved site is more difficult.
Lung Aspiration
Lung aspiration is underused and is a significantly more efficient method of obtaining a culture.
If a prominent infiltrate can be adequately localized in multiple planes, direct aspiration of the
infected lung may be performed for culture or biopsy. Lung CT scanning may facilitate such
localization.

Lung aspiration is associated with a greater risk of postprocedural air leak and usually requires a
larger-bore needle than is used to obtain pleural fluid. Because the risk associated with this
procedure is high, lung aspiration is usually 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. A lung aspirate should not be performed in patients who are on
ventilators, who have a bleeding diathesis, or who are suspected of having an infection with
Pneumocystis.

With advances in surgical techniques and increased experience, many clinicians prefer to seek
open surgical biopsy or thoracoscopic sampling in such circumstances, especially because
success and specimen size are greater and the ability to deal directly with any complication is
enhanced.

A study demonstrated positive blood cultures implicated an organism in 18% of patients


compared with 52% with positive lung aspirates. [44] The investigators compared the incidence of
positive culture results obtained with blood culture with positive culture results obtained with
lung aspiration in 100 children aged 3-58 months with pneumonia. The organisms obtained in
the blood and lung aspirate differed in 4 of 8 children in whom both culture results were positive,
suggesting that a blood culture may not always accurately reveal the lung pathogen. [44]

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.

Lung Puncture
Although used much less frequently than in previous decades, diagnostic lung puncture may still
be useful in circumstances in which pleural and subpleural lung surfaces are visibly involved and
can be well localized. [45] Risk-benefit ratio merits careful consideration given the risk of such
complications as pneumothorax, bronchopleural fistula, and hemothorax, as well as sampling a
nondiagnostic site. This is a high-risk procedure and should not be considered a routine
procedure in the diagnosis or treatment of pneumonia in the neonate.

Thoracentesis
This procedure is performed for diagnostic and therapeutic purposes in children with pleural
effusions (eg, when pleural fluid is impinging on lung or cardiac function) (see the image
below).
A breakdown of test results and
recommended treatment for pneumonia with effusion. Gm = Gram; neg = negative; pos =
positive; VATS = video-assisted thoracic surgery
View Media Gallery

In the presence of radiographically visible fluid, careful positioning of the infant and
thoracentesis after sterile preparation of the sampling site may yield diagnostic findings on Gram
stain, direct microscopy, and/or culture. If the Gram stain or the culture result from the pleural
fluid is positive or the WBC count is higher than 1000 cells/mL, by definition, the patient has an
empyema, which may require drainage for complete resolution. Ultrasonography may reveal
smaller fluid pockets and facilitate safer sampling under direct visualization. Although data from
neonates are insufficient to draw conclusions, studies in older populations suggest a very high
correlation with culture of lung tissue and/or blood. Other therapeutic decisions can be made
based on the properties of the effusion (see Complications).

The risk of pneumothorax or laceration of intercostal vessels is real but can be minimized by the
use of proper technique, including use of the Z-technique (stretching the skin down over the
entry site, so that release after the procedure will permit the return of tissues to their usual
location with occlusion of the path of the needle), entry over the superior rib margin (to
minimize inadvertent puncture of intercostal vessels) at a dependent site where fluid is most
likely to collect, continuous aspiration once the skin is penetrated, and no further advancement
once fluid is obtained.

For more information, see Infections of the Lung, Pleura, and Mediastinum.

Histology
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.

Tissue samples of lung tissue in human infants have typically been obtained from an
unrepresentative population. The sample population usually includes only infants with severe
pulmonary disease that results in death or threatens to do so or infants who die of other causes
and have coincidental sampling of the lung. Consequently, direct observations regarding
histologic changes in mild or moderate pneumonia are sparse and are often supplemented by
extrapolation from animal disease models, human adults with similar diseases, or more severe
cases in human infants that resulted in death or biopsy. Despite these limitations, certain
observations in congenital pneumonia recur, whether or not a specific pathogen is implicated. [46]

Macroscopically, the lung may have diffuse, multifocal, or very localized involvement with
visibly increased density and decreased aeration. Frankly hemorrhagic areas and petechiae on
pleural and intraparenchymal surfaces are common. Airway and intraparenchymal secretions
may range from thin and watery to serosanguineous to frankly purulent, and they are frequently
accompanied by small to moderate pleural effusions that display variable concentrations of
inflammatory cells, protein, and glucose.

Frank empyema and abscesses are unusual in newborn infants. Particulate meconium or vernix
may be visible, especially in the more proximal airways, following aspiration episodes.
Superimposed changes, such as air leak, emphysema, and sloughed airway mucosa, may be seen
as a consequence of volutrauma, pressure-related injury, oxygen toxicity, and other processes
that reflect the vigorous respiratory support often provided to these infants in an attempt to
manage derangements of gas exchange caused by the underlying illness.

With conventional microscopy, inflammatory cells are particularly prominent in the alveoli and
airways. Mononuclear cells (macrophages, natural killer cells, small lymphocytes) are usually
noted early, and granulocytes (eosinophils, neutrophils) typically become more prominent later.
Microorganisms of variable viability or particulate debris may be observed within these cells. If
systemic neutropenia is present, the number of inflammatory cells may be reduced. Alveoli may
be atelectatic from surfactant destruction or dysfunction, partially expanded with proteinaceous
debris (often resembling hyaline membranes), or hyperexpanded secondary to partial airway
obstruction from inflammatory debris or meconium.

Hemorrhage in the alveoli and in distal airways is frequent. Vascular congestion is common;
vasculitis and perivascular hemorrhage are seen less frequently. Inflammatory changes in
interstitial tissues are less common in newborns than in older individuals.

Microscopic examination of tissue following immunohistochemical staining or other molecular


biologic techniques can identify the herpes virus and an increasing number of other organisms.
In patients with TB, acid-fast bacilli are present and can be detected using the Ziehl-Neelsen
stain or can be grown on the Lowenstein-Jensen medium. Caseating granulomas are highly
suspicious, even in the absence of detectable organisms. Findings of foamy alveolar casts are
practically diagnostic for P jirovecii 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 acid-Schiff
(PAS) staining. Aspergillus and Zygomycetes species may be seen using simple hematoxylin and
eosin (H&E) staining. The specific morphology of the organisms may be diagnostic, but,
occasionally, culture or immunostaining is required.
Approach Considerations
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 (see Etiology and Clinical Presentation).

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). If therapy fails to elicit a
response, the whole treatment approach must be reconsidered.

The Pediatric Infectious Diseases Society and the Infectious Diseases Society of America created
evidence-based guidelines for the management of community-acquired pneumonia (CAP) in
infants and children older than 3 months. These guidelines discuss site-of-care management,
diagnosis, antimicrobial therapy, adjunctive surgical therapy, and prevention. While these
guidelines do not represent the only approach to diagnosis and therapy, these recommendations
may assist in decreasing morbidity and mortality rates in children with CAP. [34]

A retrospective study by Handy et al concluded that antibiotic choice for children with
community-acquired pneumonia (CAP) varied widely across practices for reasons other than the
microbiologic etiology. The study found that 40.7% of the 10,414 children in the study (4239)
received amoxicillin, however, 42.5% (4430) received macrolides, and 16.8% (1745) received
broad-spectrum antibiotics. [47, 48] Another study by Williams et al found that there was an
improvement at childrens hospitals in the use of penicillin to treat pneumonia after the
publication of the 2011 Pediatric Infectious Diseases Society/Infectious Diseases Society of
America pneumonia guideline. Before the guideline was published <10% of childrens hospitals
prescribed penicillin to treat pneumonia vs. 27.6% after publication. [49, 48]

Hospitalization
Pulse oximetry should be performed during the prehospital evaluation of children with suspected
pneumonia, and supplemental oxygen should be administered, if necessary; however, many
school-aged children do not require hospitalization and respond well to oral antibiotics. 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 are hospitalized more often, but their clinical status, degree of
hydration, degree of hypoxia, and need for intravenous therapy dictate this decision.
Hospitalization should be considered for infants who are younger than 2 months or premature
because of the risk of apnea in this age group. [50]
Children who are toxic-appearing may require resuscitation and respiratory support. Treatment
of critically ill children (those requiring ventilation) should include timely administration of
appropriate antibiotics. Delays of only a few hours in one retrospective study were associated
with significantly longer durations of ventilation, ICU stay, and total hospitalization. [51] Chest
radiography should be performed to identify the presence of an effusion/empyema (See Chest
Radiography). Drainage of a restrictive or infected effusion or empyema may enhance clearance
of the infection and improves lung mechanics. Antibiotic therapy should include vancomycin
(particularly in areas where penicillin-resistant streptococci have been identified) and a second-
or third-generation cephalosporin.

Hemodynamic Support
RBCs should be administered to ensure a hemoglobin concentration of 13-16 g/dL in the acutely
ill infant to ensure optimal oxygen delivery to the tissues. Delivery of adequate amounts of
glucose and maintenance of thermoregulation, electrolyte balance, and other elements of
neonatal supportive care are also essential aspects of clinical care.

Respiratory Management
Initial priorities in children with pneumonia include the identification and treatment of
respiratory distress, hypoxemia, and hypercarbia. Grunting, flaring, severe tachypnea, and
retractions should prompt immediate respiratory support. Children who are in severe respiratory
distress should undergo tracheal intubation if they are unable to maintain oxygenation or have
decreasing levels of consciousness. (See Pharmacologic Therapy)

Increased respiratory support requirements such as increased inhaled oxygen concentration,


positive pressure ventilation, or CPAP are commonly required before recovery begins. Bi-level
positive airway pressure (BiPAP) may also be used to help support respiratory effort as a stand-
alone intervention or as a bridge to intubation. Criteria for institution and weaning of
supplemental oxygen and mechanical support are similar to those for other neonatal respiratory
diseases. Extra humidification of inspired air (eg, room humidifiers) is also not useful, although
supplemental oxygen is frequently humidified for patient comfort.

Adequate gas exchange depends not only on alveolar ventilation, but also on the perfusion and
gas transport capacity of the alveolar perfusate (ie, blood). Preservation of pulmonary and
systemic perfusion is essential, using volume expanders, inotropes, afterload reduction, blood
products, and other interventions (eg, inhaled nitric oxide) as needed. Excellent lung mechanics
do little good if perfusion is not simultaneously adequate.

Be aware that lung disease is often structurally heterogeneous, with subpopulations of normally
inflated, hyperinflated, atelectatic, obstructed, fluid-filled, and variably perfused alveoli that may
require multiple adjustments of ventilatory pressures, flows, rates, times, and modalities.

Chest percussion
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.

Pharmacologic Therapy
The choice of an initial, empiric agent is selected according to the susceptibility and resistance
patterns of the likely pathogens and experience at the institution, and the selection is tempered by
knowledge of delivery of drugs to the suspected infected sites within the lung.

Antibiotic agents

The vast majority of children diagnosed with pneumonia in the outpatient setting are treated with
oral antibiotics.

High-dose amoxicillin is used as a first-line agent for children with uncomplicated community-
acquired pneumonia, which provides coverage for S pneumoniae. Second- or third-generation
cephalosporins and macrolide antibiotics such as azithromycin are acceptable alternatives but
should not be used as first-line agents because of lower systemic absorption of the
cephalosporins and pneumococcal resistance to macrolides. Treatment guidelines are available
from the Cincinnati Children's Hospital Medical Center [52] and, more recently, from the
Infectious Diseases Society of America (IDSA). [34]

Macrolide antibiotics are useful in school-aged children, because they cover the most common
bacteriologic and atypical agents (Mycoplasma, Chlamydophila, Legionella). However,
increasing levels of resistance to macrolides among pneumococcal isolates should be considered
(depending on local resistance rates). One study suggests that penicillin and macrolide resistance
among S pneumoniae isolates has been increasing. [53]

Hospitalized patients can be safely treated with narrow-spectrum agents such as ampicillin, and
this is the mainstay of current guidelines for pediatric community-acquired pneumonia. [54, 55, 34]
Children who are toxic appearing should receive antibiotic therapy that includes vancomycin
(particularly in areas where penicillin-resistant pneumococci and methicillin-resistant S aureus
[MRSA] are prevalent) along with a second- or third-generation cephalosporin.

If gram-negative pneumonia is suspected and beta-lactam antibiotics are administered, some data
suggest that continuous exposure to an antimicrobial concentration greater than the mean
inhibitory concentration (MIC) for the organism may be more important than the amplitude of
the peak concentration. Intramuscular treatment or intravenous therapy with the same total daily
dose but a more frequent dosing interval may be advantageous if the infant's condition fails to
respond to conventional dosing. Comparative data to confirm the superiority of this approach are
lacking. Whether this approach offers any advantage with use of agents other than beta-lactams
is unclear.

Studies in human adults have demonstrated that aminoglycosides reach the bronchial lumen
marginally when administered parenterally, although alveolar delivery is satisfactory. [56, 57]
Endotracheal treatment with aerosolized aminoglycosides has been reportedly effective for
marginally susceptible organisms in bronchi, whereas cefotaxime appears to attain adequate
bronchial concentrations via the parenteral route. Limited in vitro and animal data suggest that
cefotaxime may retain more activity than aminoglycosides in sequestered foci, such as abscesses,
although such foci are rare in congenital pneumonia, and adequate drainage may be more
important than antimicrobial selection.

Recovery of a specific pathogen from a normally sterile site (eg, blood, urine, CSF) permits
narrowing the spectrum of antimicrobial therapies and may thus reduce the selection of resistant
organisms and costs of therapy. Repeated culture of the site after 24-48 hours is usually
warranted to ensure sterilization and to assess the efficacy of therapy. Endotracheal aspirates are
not considered to represent a normally sterile site, although they may yield a pathogen that is a
true invasive culprit. Reculture of an endotracheal aspirate that identified the presumptive
pathogen in a particular case may not be helpful because colonization may persist even if tissue
invasion has been terminated.

Decreasing respiratory support requirements, clinical improvement, and resolution revealed on


radiographs also support the efficacy of therapy. When appropriate, assess plasma antibiotic
concentrations to ensure adequacy and reduce the potential for toxicity. Failure to recover an
organism does not exclude an infectious etiology; continuation of empiric therapy may be
advisable unless the clinical course or other data strongly suggests that a noninfectious cause is
responsible for the presenting signs.

Continue to perform careful serial examinations for evidence of complications that may warrant
a change in therapy or dosing regimen, surgical drainage, or other intervention.

Anti-inflammatory therapy

Evidence-supported options for targeted treatment of inflammation independent of antimicrobial


therapy are severely limited. [58] Considerable speculation suggests that current antimicrobial
agents, directed at killing invasive organisms, may transiently worsen inflammatory cascades
and associated host injury because dying organisms release proinflammatory structural and
metabolic constituents into the surrounding microenvironment. This is not to imply that
eradicating invasive microbes should not be a goal; however, other methods of eradication or
methods of directly dealing with the pathologic inflammatory cascades await further definition.
In pneumonia resulting from noninfectious causes, the quest for targeted, effective, and safe anti-
inflammatory therapy may be of even greater importance.

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. [59] Until definitive studies are performed, steroids
should not be routinely used for uncomplicated pneumonia.

Antiviral agents

Most infants with respiratory syncytial virus (RSV) pneumonia do not require antimicrobials.
Serious infections with this organism usually occur in infants with underlying lung disease.

Influenza A viruses, including 2 subtypes (H1N1) and (H3N2), and influenza B viruses currently
circulate worldwide, but the prevalence of each 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 [Tamiflu], zanamivir, amantadine, rimantadine) are approved for
treatment and chemoprophylaxis of influenza.

Influenza A pneumonia that is particularly severe or when it occurs in a high-risk patient may be
treated with zanamivir or oseltamivir. The neuraminidase inhibitors have activity against
influenza A and B viruses, whereas the adamantanes have activity against only influenza A
viruses.

Check for resistance patterns for other antiviral agents indicated for treatment or
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.

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.

These prompted the US Centers for Disease Control and Prevention (CDC) to issue revised
interim recommendations for antiviral treatment and prophylaxis of influenza. 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.

Complete recommendations are available from the CDC.

Herpes simplex virus pneumonia is treated with parenteral acyclovir.

CMV pneumonitis should be treated with intravenous ganciclovir or foscarnet.

Invasive fungal infections, such as those caused by Aspergillus or Zygomycetes species, are
treated with amphotericin B or voriconazole.
Bronchodilators

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 does not respond to
bronchodilator. However, infants or children with reactive airway disease or asthma may react to
a viral infection with bronchospasm, which responds to bronchodilators.

Management of Pleural Effusions


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 (see Thoracentesis). 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.

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. Video-assisted thoracic surgery (VATS)
procedure may be performed for decortication of organized empyema or loculated effusions.

For more information, see Infections of the Lung, Pleura, and Mediastinum.

Nutritional Support
Attempts at enteral feeding often are withheld in favor of parenteral nutritional support until
respiratory and hemodynamic status is sufficiently stable.

Complications
Severe respiratory compromise may require intubation and transfer to a suitable intensive care
unit (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.

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.

Other complications include the following:

Pleural effusion
Empyema
Pneumatocele
Lung abscess
Necrotizing pneumonia
Systemic infection with metastatic foci
Persistent newborn pulmonary hypertension
Air leak syndrome, including pneumothorax, pneumomediastinum, pneumopericardium,
and pulmonary interstitial emphysema
Airway injury
Obstructive airway secretions
Hypoperfusion
Chronic lung disease
Hypoxic-ischemic and cytokine-mediated end-organ injury
Sepsis

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 HIB
vaccine, the rates of HIB pneumonia have significantly declined. However, the diagnosis 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) that was introduced in 2000 contains epitopes to 7 different strains.
Pneumococcal vaccine polyvalent (Pneumovax) covers 23 different strains. A new 13-valent
conjugated vaccine (Prevnar 13) was approved in 2010 and replaces PCV7 for all doses.
Children who have completed their vaccine schedule with PCV7 should get a booster dose with
PCV13.

In a study to evaluate the effectiveness of heptavalent pneumococcal conjugate vaccine in


prevention of pneumonia in children younger than 5 years, Black et al showed a 32.2% reduction
in the first year of life and a 23.4% reduction between 1-2 years, but only a 9.1% reduction in
children older than 2 years. [60, 21]

However, since the initiation of the heptavalent pneumococcal vaccine in 2000, researchers have
found that nearly two thirds of invasive pneumococcal disease cases in young children have been
caused by 6 serotypes not included in that vaccine. Those serotypes, along with the original 7,
have been incorporated into pneumococcal vaccine valent-13 (Prevnar 13), which was approved
in February 2010. [61]

A paper at the 33rd Annual Meeting of the European Society for Paediatric Infectious Diseases
reports on the impact of the 10-valent pneumococcal conjugate vaccine, PCV10, in unvaccinated
children. The study assessed pneumonia rates from 2011 to 2013 in 116,672 children and found
that for hospital-diagnosed pneumonia, there was a relative rate reduction of 12% in the 2012/13
season, compared with the 2005/06 and 2007/08 seasons. For hospital-treated primary
pneumonia, there was a relative rate reduction of 28% in the 2012/13 season, compared with the
2005/06 and 2007/08 seasons. [62]

The 23-valent polysaccharide vaccine (PPVSV) is recommended for children 24 months or older
who are at high risk of pneumococcal disease.

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; MedImmune), administered as a nasal spray, which is
currently licensed only for persons aged 2-49 years.

Although the influenza vaccine is especially recommended for children at high risk, such as
those with 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 mo or older) to help protect this high-risk, but unvaccinated, population. The safety
and efficacy of this approach remains unknown.

PCP prophylaxis with trimethoprim-sulfamethoxazole 3 times a week is widely used in


immunocompromised children and has all but eradicated this organism in patients receiving
prophylaxis.

The use of pneumococcal and H influenzae type B vaccines and penicillin prophylaxis in patients
with sickle cell disease have helped reduce the incidence of bacterial infections in these children.

RSV prophylaxis consists of monthly intramuscular injections of palivizumab at a dose of 15


mg/kg (maximum volume 1 mL per injection; multiple injections may be required per dose).
This strategy is currently recommended for high-risk infants only (ie, premature infants and
newborns with congenital heart disease). 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.

Malnutrition is a known risk factor for infections, but zinc deficiency in particular has been
shown to increase the risk for childhood pneumonia. In areas of the world where zinc deficiency
is common, supplementation may significantly reduce the incidence of childhood pneumonia. [63]

Consultations

Consultation is not needed in the care of most children with pneumonia. However, children who
have underlying diseases may benefit from consultation with the specialist involved in their
long-term care. For example, most children with cystic fibrosis are monitored by a
pulmonologist.

Consultation with a pediatric infectious disease specialist may be appropriate in the treatment of
a child with persistent or recurrent pneumonia, and children with pleural effusions or empyema
should be referred to a tertiary medical center, where thoracentesis can be performed. This
procedure may be performed in an emergency department setting and may require subspecialty
consultation.

Long-term Monitoring
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.

Careful longitudinal surveillance for long-term problems with growth, development, otitis,
reactive airway disease, and other complications should be performed

Medication Summary
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. Beta-lactam antibiotics (eg, amoxicillin, cefuroxime,
cefdinir) are preferred for outpatient management. Macrolide antibiotics (eg, azithromycin,
clarithromycin) are useful in most school-aged children to cover the atypical organisms and
pneumococcus. Local variations in resistance require different approaches to therapy, including
cases caused by pneumococcus. Any child with a positive purified protein derivative (PPD) test
result and infiltrate on chest radiographs requires additional testing for tuberculosis and
polymicrobial treatment.
Agents typically used initially in the treatment of newborns and young infants with pneumonia
include a combination of ampicillin and either gentamicin or cefotaxime. The selection of
cefotaxime or gentamicin must be based on experience and considerations at each center and in
each patient. Combination therapy provides reasonable antimicrobial efficacy against the
pathogens that typically cause serious infection in the first days of life. Other agents or
combinations may be appropriate for initial empiric therapy if justified by the range of pathogens
and susceptibilities encountered in a particular clinical setting.

Isolation of a specific pathogen from a normally sterile site in the infant allows revision of
therapy to the drug that is least toxic, has the narrowest antimicrobial spectrum, and is most
effective. Dosing intervals for ampicillin, cefotaxime, gentamicin, and other antimicrobial agents
typically require readjustment in the face of renal dysfunction or once the infant is older than 7
days (if the infant still requires antimicrobial therapy).

In a randomized, placebo-controlled study of 820 pediatric patients with mild pediatric


pneumonia, researchers found that treatment with oral amoxicillin (50 mg/kg/day) twice daily
was as effective as amoxicillin given three times a day. Treatment failure occurred in 23% of the
twice-daily group and 22.8% of the thrice-daily group in the intention-to-treat analysis, and in
21.3% and 20.1% of these groups, respectively, in the per-protocol analysis. Among the 277
patients with radiologically confirmed pneumonia, treatment failure occurred in 18.8% of
patients in both groups. [64, 65]

Penicillins
Class Summary

The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate
concentrations and inhibit the biosynthesis of cell wall mucopeptide. Examples of penicillins
include amoxicillin (Amoxil, Trimox), penicillin VK, and ampicillin.

Amoxicillin (Amoxil, Trimox)

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Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication,
resulting in bactericidal activity against susceptible bacteria. This drug is an appropriate first-line
agent in children in whom pneumococcal disease is strongly suspected. Amoxicillin offers the
advantages of being relatively palatable and having a tid-dosing schedule, but it has limited
activity against gram-negative bacteria due to resistance.

Ampicillin (Marcillin, Omnipen, Polycillin)

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Ampicillin has bactericidal activity against susceptible organisms and is used as an alternative to
amoxicillin when patients are unable to take medication orally.

Penicillin VK (Beepen-VK, Pen Vee K)

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Penicillin VK inhibits the biosynthesis of cell wall mucopeptide and is bactericidal against
sensitive organisms when adequate concentrations are reached. This drug is most effective
during the stage of active multiplication, but inadequate concentrations may produce only
bacteriostatic effects. Penicillin VK may be used as an alternative to amoxicillin in the treatment
of outpatients with pneumonia in whom pneumococcal disease is strongly suspected, but it has
limited activity against gram-negative bacteria.

Cephalosporins
Class Summary

Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit


bacterial cell wall synthesis, resulting in bactericidal activity. Cephalosporins are divided into
first, second, and third generation. First-generation cephalosporins have greater activity against
gram-positive bacteria, and succeeding generations have increased activity against gram-negative
bacteria and decreased activity against gram-positive bacteria.

Cefpodoxime (Vantin)

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Cefpodoxime inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-
binding proteins. The tablet should be administered with food.

Cefprozil (Cefzil)

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Cefprozil binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall
synthesis and results in bactericidal activity.

Cefdinir (Omnicef)

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Cefdinir binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall
synthesis and results in bactericidal activity.
Ceftriaxone (Rocephin)

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Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity that


arrests bacterial growth by binding to one or more penicillin-binding proteins. Ceftriaxone has
lower efficacy against gram-positive organisms but higher efficacy against resistant organisms.

Cefotaxime (Claforan)

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Cefotaxime is a third-generation cephalosporin with gram-negative spectrum that arrests


bacterial cell wall synthesis, which, in turn, inhibits bacterial growth. This drug has a lower
efficacy against gram-positive organisms.

Cefuroxime (Zinacef, Ceftin, Kefurox)

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Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity first-


generation cephalosporins have. This drug adds activity against P mirabilis, H influenzae, E coli,
K pneumoniae, and M catarrhalis. The condition of the patient, severity of infection, and
susceptibility of the causative microorganism determines the proper dose and route of
administration.

Ceftaroline (Teflaro)

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Beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic
gram-negative bacteria. It is indicated in children aged 2 months for treatment of community-
acquired bacterial pneumonia (CABP) caused by susceptible isolates of Streptococcus
pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-
susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca,
and Escherichia coli.

Glycopeptides
Class Summary

Anti-infectives such as vancomycin are effective against some types of bacteria that have
become resistant to other antibiotics.

Vancomycin (Vancocin)
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Vancomycin is a tricyclic glycopeptide antibiotic with bactericidal action that primarily results
from the inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial cell
membrane permeability and RNA synthesis. Antibiotic therapy should include vancomycin
(particularly in areas where penicillin-resistant streptococci have been identified) and a second-
or third-generation cephalosporin.

Macrolide Antibiotics
Class Summary

Macrolide antibiotics have bacteriostatic activity and exert their antibacterial action by binding to
the 50S ribosomal subunit of susceptible organisms, resulting in inhibition of protein synthesis.

Erythromycin-sulfisoxazole (Pediazole)

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Erythromycin is a macrolide antibiotic with a large spectrum of activity that binds to the 50S
ribosomal subunit of the bacteria, which inhibits protein synthesis. Sulfisoxazole expands
erythromycin's coverage to include gram-negative bacteria and inhibits bacterial synthesis of
dihydrofolic acid by competing with para-aminobenzoic acid (PABA). The dose for the
combination of the 2 drugs is based on the erythromycin component.

Azithromycin (Zithromax)

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Azithromycin is used to treat mild to moderate microbial infections. Bacterial or fungal


overgrowth may result with prolonged antibiotic use.

Clarithromycin (Biaxin)

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Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA


from ribosomes, causing RNA-dependent protein synthesis to arrest.

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

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Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA


from ribosomes, causing RNA-dependent protein synthesis to arrest. This drug is used for the
treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of
infection determine the proper dosage. When bid dosing is desired, half-total daily dose may be
taken q12h. For more severe infections, double the dose.

Aminoglycosides
Class Summary

Aminoglycosides are bactericidal antibiotics used to primarily treat gram-negative infections.


They interfere with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

Gentamicin

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Gentamicin is an aminoglycoside antibiotic for gram-negative coverage that is typically used in


combination with agents against gram-positive organisms. When administered parenterally, this
agent offers antimicrobial efficacy against many gram-negative pathogens commonly
encountered in the first few days of life, including E coli, Klebsiella species, and other enteric
organisms, as well as many strains of nontypeable H influenzae.

Gentamicin is also variably effective against some strains of certain gram-positive organisms,
including S aureus, enterococci, and L monocytogenes. Gentamicin crosses the blood-brain
barrier into the CNS less well and theoretically poses a greater risk of renal toxicity or
ototoxicity than cefotaxime and other third-generation cephalosporins, which are the common
alternatives.

Gentamicin is associated with much less rapid emergence of resistant organisms in a closed
environment (eg, neonatal ICU), and has a broader range of susceptible gram-negative
organisms. Gentamicin has been reported to offer additive or synergistic activity against
enterococci when used with ampicillin.

Antituberculosis Agents
Class Summary

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)

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Isoniazid has the best combination of effectiveness, low cost, and minor side effects of this class
of drugs. Isoniazid should be the first-line agent unless the patient has known resistance or
another contraindication. Therapeutic regimens for less than 6 months 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.

Ethambutol (Myambutol)

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Ethambutol diffuses into actively growing mycobacterial cells, such as tubercle bacilli and
impairs cell metabolism by inhibiting synthesis of one or more metabolites, which, in turn,
causes cell death.

No cross-resistance has been demonstrated; however, mycobacterial resistance is common with


previous therapy. Use ethambutol in these patients in combination with second-line drugs that
have not been previously administered. Administer q24h until permanent bacteriologic
conversion and maximal clinical improvement is observed. Absorption of this drug is not
significantly altered by food.

Rifampin (Rifadin, Rimactane)

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Rifampin is used in combination with at least one other antituberculous drug and inhibits RNA
synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which
in turn blocks RNA transcription. Rifampin treatment duration is for 6-9 months or until 6
months have elapsed from conversion to sputum culture negativity.

Streptomycin

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Streptomycin sulfate is used in combination with other antituberculous drugs (eg, isoniazid,
ethambutol, rifampin). The total period of treatment for TB is a minimum of 1 year; however,
indications for terminating streptomycin therapy may occur at any time. Streptomycin is
recommended when less potentially hazardous therapeutic agents are ineffective or
contraindicated.

Pyrazinamide

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Pyrazinamide is a pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal
against Mycobacterium tuberculosis, depending on the concentration of the drug attained at the
site of infection. Its mechanism of action is unknown.

For patients who are drug susceptible, administer for the initial 2 months of a 6-month or longer
treatment regimen. Treat patients who are drug resistant with individualized regimens.

Antiviral Agents
Class Summary

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.

Unfortunately, oseltamivir resistance emerged in the United States during the 2008-2009
influenza season; the CDC issued revised interim recommendations for antiviral treatment and
prophylaxis of influenza. Thus, zanamivir (Relenza) is recommended as the initial choice for
antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. Complete
recommendations are available from the CDC.

Ribavirin (Virazole)

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Ribavirin inhibits viral replication by inhibiting DNA and RNA synthesis and is effective against
RSV, influenza virus, and herpes simplex virus. However, there has been little evidence to
demonstrate that ribavirin has much clinical benefit in a hospital setting.

Oseltamivir (Tamiflu)

View full drug information

Oseltamivir 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,
oseltamivir decreases the release of viruses from infected cells and, thus, viral spread. This drug
has been effective for treatment of influenza A or B infection and is administered within 40 h of
symptom onset.

Unfortunately, oseltamivir resistance emerged in the United States during the 2008-2009
influenza season; the CDC issued revised interim recommendations for antiviral treatment and
prophylaxis of influenza. Thus, zanamivir (Relenza) is recommended as the initial choice for
antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. Complete
recommendations are available from the CDC.
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.

Zanamivir (Relenza)

View full drug information

Zanamivir is an 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.
Zanamivir is effective against both influenza A and B and is administered by inhalation through
a Diskhaler oral inhalation device. Circular foil discs that contain 5-mg blisters of drug are
inserted into supplied inhalation device.

Acyclovir (Zovirax)

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Acyclovir inhibits activity of both HSV-1 and HSV-2 and is the drug of choice for the treatment
of pneumonia in children with herpes viruses (eg, herpes simplex, varicella). Patients experience
less pain and faster resolution of cutaneous lesions when used within 48 hours from rash onset.

Vaccines
Class Summary

Aside from avoiding infectious contacts, vaccination is the primary mode of prevention.
Vaccines provide immunity to a disease by stimulating antibody formation and can be either
killed or attenuated live.

Influenza virus vaccine (Fluzone)

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Influenza vaccine is recommended for children aged 6 months and older. The 2 forms of the
vaccine are (1) an inactivated vaccine (various products), administered as an intramuscular
injection and (2) a cold-adapted attenuated vaccine (FluMist; MedImmune), administered as a
nasal spray, which is currently licensed only for persons aged 2-49 years.

13-valent conjugated pneumococcal vaccine (PCV13, Prevnar)

View full drug information


The pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein; Prevnar) contains
epitopes to 13 different strains.
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