Pneumonia, an inflammatory process affecting the lung parenchyma, is usually due to an infectious etiology (Table 37-1). Signs and symptoms such as rales, cough, and fever may lead to a clinical diagnosis of pneumonia. Pneumonia is usually diagnosed by an abnormal chest radiograph (CXR). The clinical spectrum of pneumonia varies from mild to life-threatening disease with significant morbidity and mortality. Given the large numbers of agents that cause pneumonia, and limitations of diagnostic testing, the exact cause is often unknown. However, a constellation of clinical, radiologic, and laboratory findings may suggest a likely pathogen, and therefore appropriate therapy (Table 37-2).

Health care–associated pneumonia (HCAP) is pneumonia in patients hospitalized for >2 days within the last 90 days, in a nursing home or long-term care facility resident, on hemodialysis, on immunosuppressive therapy, or who have had wound care within the last 30 days. Hospital-acquired pneumonia (HAP) is pneumonia that occurs >48 hours after hospital admission. Ventilator-associated pneumonia (VAP) is pneumonia that occurs after the first 48 to 72 hours of endotracheal intubation. Community-acquired pneumonia (CAP) is pneumonia in patients who do not meet the criteria for HCAP, HAP, or VAP.¹

Pneumonia is the most common infectious cause of death in children worldwide. It is the leading cause of death in children <5 years of age, killing nearly 1 million children each year. The majority of deaths occur in the developing world.^2,3 According to the World Health Organization (WHO), pneumonia occurs in 150.7 million children <5 years annually, with about 20 million requiring hospitalization.⁴

Pediatric pneumonia has a significant morbidity and financial burden, although the mortality rate in developed countries is low: <1 per 1000 per year. Estimated medical costs are $1 billion annually in the United States.⁵ In Europe annually there are an estimated 2.5 million cases of CAP.³ In the United States, pneumonia ranks second to trauma as the most frequent cause for hospitalization in 1- to 18-year-old children.³ For the United States population, 1 to 21 years, respiratory diseases, including pneumonia and asthma, are second to pregnancy/childbirth as the most common cause of hospitalization.⁶

According to the Nationwide Emergency Department Sample, 25.5% of pediatric emergency department (ED) visits for pneumonia were admitted.⁷ In a given year, there are approximately 375,000 ED visits for CAP in children ≤18 years, with 20% hospitalized.⁸ The highest rate of hospitalization is in the very young, with the incidence decreasing with increasing age. The annual age-related incidence of pneumonia-related hospitalization (cases per 10,000 children) is 62.6, 23.8, 10.1, and 4.2 for ages <2, 2 to 4, 5 to 9, and 10 to 17 years, respectively.⁵

Pneumonia is “the most common ambulatory care-sensitive condition that results in hospitalization.” Pneumonia accounts for >1 million pediatric outpatient clinic visits annually. Approximately 8% of children who receive ambulatory care for pneumonia are admitted.⁹

Of childhood ED visits in the United States, acute upper respiratory infection (URI) is the commonest diagnosis (11.6%) and pneumonia is 1.8%, of which 21.4% are admitted.¹⁰

The presentation of pneumonia varies depending on age, comorbidity, risk factors, severity, and causative microorganism. The triad of fever, cough, and rales often present in adults and adolescents is rarely present in infants or young children.¹¹ In neonates, nonspecific signs and symptoms—e.g., lethargy, irritability, apnea, vomiting, poor feeding, isolated fever or hypothermia, and poor muscle tone—are more common, and frequently occur as part of a sepsis syndrome.

Infants often present with nonspecific signs and symptoms. They may have fever without source, sepsis, vital sign abnormalities (fever, hypothermia, bradycardia, tachycardia, tachypnea), gastrointestinal symptoms (poor feeding, vomiting, diarrhea, abdominal pain), respiratory distress, lethargy, and shock. Infants with a bacterial pneumonia may be febrile and in respiratory distress with tachypnea, retractions, and hypoxia, whereas infants with Chlamydophila pneumoniae may be afebrile with a normal examination with only a cough.

Toddlers frequently have a fever and cough, although gastrointestinal complaints such as vomiting or abdominal pain are common and may be the presenting complaint.¹¹ The presentation in older children and adolescents is similar to adults, with cough, pleuritic chest pain, and generalized symptoms from abdominal pain to headache.

There are two sometimes overlapping presentations: “typical” and “atypical.” Typical pneumonia, from a bacterial etiology, has sudden onset of fever, chills, pleuritic chest pain, productive cough, a toxic appearance, and rales. Atypical pneumonia, from a virus or atypical bacteria (Mycoplasma or Chlamydophila), has a gradual onset of low-grade fever, non-productive cough, malaise, and headache. Examination may reveal wheezing, viral enanthem, or URI with rhinitis, pharyngitis, and conjunctivitis. Determination of the etiologic agent from presentation alone is difficult.

Presentation usually indicates pneumonia severity and need for hospitalization or outpatient management. The patient with respiratory distress or an altered mental status typically requires hospitalization. Patients with risk factors such as immunosuppression or chronic disease, including chronic lung disease (CLD) of infancy, congenital heart disease, and sickle cell disease, generally have a more serious life-threatening pneumonia.

Although rales, decreased breath sounds, and wheezing may be heard, such findings may be absent. Rales may not be present in infants/young children because of poor inspiration, poor ventilation, transmitted sounds throughout the chest which preclude localization, and noisy upper-airway sounds. A prospective study in children with radiologically confirmed CAP found 19% had no symptoms other than fever, and 28% had normal lung auscultation.¹²

Respiratory distress with hypoxia and/or increased work of breathing (retractions, grunting, flaring, head bobbing, or paradoxical [seesaw] breathing) may be present. Abdominal pain or distention from swallowed air, ileus, or diaphragmatic irritation from lower lobe pneumonia may occur. Meningismus without meningeal infections can occur with upper lobe pneumonia.

Other findings may be useful in detecting contiguous or hematogenous spread, and in diagnosing comorbidity such as immunosuppression or chronic disease. Extrapulmonary findings suggesting specific etiologic agents may occur. Examples include conjunctivitis with Chlamydophila, pharyngitis with streptococcal or mycoplasma infections, a preceding or coexistent URI, and skin exanthemas. Examination may reveal complications including dehydration, pleural effusion, respiratory failure, or sepsis.

Tachypnea may be an isolated finding, especially in infants and young children. WHO defines tachypnea as a respiratory rate (RR) >60 breaths/min in infants <2 months old, >50 in infants 2 to 12 months old, >40 >1- to 4-year-olds, and >30 in children >5 years old.¹³ By this definition, tachypnea was present in 50% to 80% of pediatric CAP patients confirmed by CXR (74% sensitivity, 76% specificity).¹³ The presence versus the absence of tachypnea increases the likelihood of pneumonia,^14–18 but it is not always a predictor of pneumonia in infants and children.^19,20

In bacteremic pediatric patients with pneumococcal pneumonia, tachypnea was found in only 19%.²¹ Despite conflicting reports, absence of tachypnea has been purported as the best finding for ruling out pneumonia.²² “Tachypnea remains the most consistent clinical manifestation of pediatric pneumonia above all in developing countries.”¹¹

A Canadian task force suggested that absence of respiratory distress, tachypnea, crackles, and decreased breath sounds excluded pneumonia.²³ An attempt to validate this guideline found 45% sensitivity, 66% specificity, 25% positive predictive value, and 82% negative predictive value.²⁴ Another study looking at predictive factors for pneumonia in a pediatric ED had very poor specificity (8%) but excellent sensitivity (98%). Statistically significant variables associated with pneumonia were history of fever, tachypnea, decreased breath sounds, crackles, grunting, or retractions. Fever and tachypnea had 93% sensitivity.²⁵ Tachypnea is nonspecific and has many causes including fever, pain, anxiety, respiratory disease other than pneumonia, heart disease, and metabolic disease. Tachycardia has many causes. Significant tachycardia above the child’s normal range and fever suggests pneumonia. Mean pulse oximetry was not a predictor of pneumonia in another study.²⁶ A study evaluating hospitalized children with CAP found that fever >38.4°C and the presence of a pleural effusion had 79% sensitivity and 59% specificity for bacterial pneumonia, and wheezing was more frequent in viral or atypical (41%) versus bacterial pneumonia (14%).²⁷ Rales, RR >60 breaths/min, and an absolute band count >1500/mm³ had an 85% sensitivity and a 59% specificity and predicted 85% of lobar pneumonia in febrile infants <60 days of age.²⁸ Leukocytosis (WBC >20,000 mm³) in febrile (>39.0°C) children <5 years old detected 26% of patients with lobar pneumonia who had no physical examination signs of pneumonia.²⁹

The American College of Emergency Physicians (ACEP) pediatric fever clinical policy recommends obtaining a CXR in febrile infants or children 2 months to 2 years with any of the following: cough, hypoxia, rales, fever ≥39°C, fever duration >48 hours, or tachycardia and tachypnea out of proportion to fever.³⁰

Processes that impair host defense mechanisms predispose to pneumonia. This includes congenital (e.g., tracheoesophageal fistula) or acquired (e.g., human immunodeficiency virus) disorders, respiratory diseases (CLD of infancy, cystic fibrosis), non-pulmonary diseases (muscular dystrophy, cerebral palsy, or congestive heart failure), systemic diseases (malignancy) and iatrogenic (anesthesia, sedation, medications or invasive upper airway/lungs/chest procedures). Environmental factors, e.g., household smokers, are associated with an increased incidence and severity of respiratory infections.

A preceding viral URI may be the most common predisposing condition for pediatric pneumonia. URIs suppress the host’s normal respiratory anatomic and physiologic mechanisms. URIs damage the normal respiratory epithelium that acts as a cellular barrier, alter the native bacterial flora in the upper respiratory tract (URT), impair the mucociliary system, and inhibit phagocytosis.

Host defense mechanisms are designed to keep the lower respiratory tract (LRT) sterile. Microbes reach the lung after aspiration from the URT (most common), via bloodstream, contiguous spread, or after chest/upper airway surgery procedures.

Respiratory epithelium serves as a barrier. Mucociliary apparatus clears foreign materials including microorganisms from the airway. Coughing, a physiologic reflex, acts to clear material from the respiratory tract. Lymphatic channels drain microorganisms to regional lymph nodes where macrophages act to clear them.

Neutrophils migrate into the lung to clear bacteria. Viruses and intracellular pathogens are attacked by the host’s cell-mediated immunity.

Secretory immunoglobulins, particularly IgA, augment bacterial lysis and neutralize various toxins and viruses. Accumulation of inflammatory cells and fluids causes the clinical and radiologic manifestations of pneumonia.

Neutrophils travel from pulmonary capillaries into the lung’s airspaces and kill microorganisms by two mechanisms: phagocytosis or by neutrophil extracellular trap (NET).³¹ Neutrophils use reactive oxygen species, antimicrobial proteins, and degradative enzymes to kill ingested microorganism. Neutrophils extrude NET, a meshwork of chromatin that contains antimicrobial proteins. NET traps and kills the extracellular microbe.

Pathogens try to escape these defense mechanisms. Pneumococci avoid recognition by lung epithelial cells by misleading or avoiding the pattern recognition receptors on lung cells. Streptococcus pneumoniae contain pneumolysin, a protein that allows the microbe to kill the host cell. These processes in turn activate the complement system, leading to an inflammatory response.

Inflammation, essential for host defense mechanisms, may result in lung injury. Substances produced by neutrophils may kill lung cells and destroy host tissues. The host’s inflammatory response causes cellular migration and the secretion of fluids that interfere with gas exchange across alveolar capillary membranes and noncardiogenic pulmonary edema, respiratory distress/failure, and acute respiratory distress syndrome (ARDS). When respiratory epithelium is infected, host cells may be killed, protective ciliary activity destroyed, and dead cells slough into the airway. This narrows the airway, causing hyperinflation, air trapping, and increased dead space ventilation. The inflammatory response and destroyed epithelial cells lead to atelectasis with intrapulmonary shunting, hyaline membrane formation, and noncardiogenic pulmonary edema.

The causative microorganism is often unknown. This may improve in the future with better diagnostic testing.^32,33 In hospitalized children with LRT infections, a pathogen was identified in 79% to 85% of children.^31,34,35 Testing included bacterial cultures, viral cultures, direct fluorescent antibody (DFA) test, polymerase chain reaction (PCR), and serology on nasopharyngeal swabs, blood, bronchoalveolar lavage, tracheal aspirate, and pleural fluid. This extensive testing is not cost-effective and is infrequently done in clinical practice. Despite advances in diagnostic testing, “there are still a significant number of cases (20–50%) in which … the (etiologic) agent is not identified.”³³

It is difficult to differentiate viral from bacterial infections. This may improve in the future by using an analysis of host gene expression profiles concomitantly with comprehensive microbiologic diagnostic assays.^3,36,37 Studies using gene expression profiles of peripheral blood leukocytes have been promising.³

One caveat to remember: detection of a pathogen does not necessarily mean that organism is the cause of the infection. An elevated acute serology sample may denote a prior infection, thus the need for paired serology samples. Nasal carriage of some organisms occurs. They may not be the etiologic agent of the pneumonia. Yield for sputum and blood cultures may be low, especially for fastidious, difficult-to-grow organisms. Some organisms need special culture material and handling, and may take days or weeks to grow. Coexistence of pathogens is quite common, with concomitant viral/viral or viral/bacterial infections occurring in infants and children up to 73% of the time.^5,38 Mixed infections or co-infections (polymicrobial CAP) may be associated with more severe disease.³⁶ The isolated virus or bacteria may be part of a coexistent infection, or a “bystander,” and not a cause of the pneumonia.³⁸

The term atypical pneumonia arose in the 1940s, when the sulfonamides and penicillins were introduced. The term referred to pneumonia that did not respond to these antimicrobials and no organism was identifiable by Gram stain or culture. Atypical bacteria do not color with Gram staining. They are neither Gram stain–positive nor negative (colorless). With improved diagnostic techniques, organisms that cause atypical pneumonia have been identified. Examples include viruses, Mycoplasma pneumoniae, Chlamydophila (previously Chlamydia) pneumoniae, Legionella, and Pneumocystis.³⁹ Atypical pneumonias are characterized by failure to identify an etiologic agent on routine Gram stain or sputum culture and a non-lobar, patchy, or interstitial pattern on CXR.

The pathogen responsible for pediatric CAP depends upon age, comorbidity, immunizations, daycare attendance, and epidemiologic factors including seasonal variations and recent local outbreaks. There is a seasonal variation. The incidence of pneumonia peaks in the winter in the Northern Hemisphere. If the causative organism cannot be determined, age is the best predictor of the pathogen (Table 37-3).

Viruses are the most common cause of pediatric pneumonia.^5,33,35 S. pneumoniae is the most common pediatric bacterial pneumonia. Respiratory syncytial virus (RSV) is the most frequent viral cause. M. pneumoniae is the most common “atypical” bacterial pneumonia, followed by C. pneumoniae.^5,35

A causative pathogen for CAP was identified in 84.2% children and adolescents in a European population with high (85%) pneumococcal conjugate vaccine coverage. Viruses were most common (63.4%). Pneumococcus was the most common bacterial pathogen (11.3%), followed by Mycoplasma (7.5%). In children <5 years old RSV was the most common pathogen. Mycoplasma was the most frequent cause in older children.³⁵

A US study of CAP in children requiring hospitalization found a median age of 2 years and an annual incidence of 15.7 cases per 10,000 children; 21% required intensive care and <1% died. A pathogen was detected in 81%, with one or more viruses in 66%, bacterial pathogens in 15%: one or more bacteria in 8%, both bacterial and viral pathogens in 7%. The most common pathogens were RSV 28%, human rhinovirus 27%, human metapneumovirus (hMPV) 13%, adenovirus 11%, M. pneumonia 8%, influenza 7%, parainfluenza 7%, coronavirus 5%, S. pneumonia 4%, S. aureus 1%, and S. pyogenes 1%. The remaining pathogens were (highest to lowest frequency) S. pyogenes, S. viridans, Chlamydophila, Haemophilus influenza, other gram-negative bacteria, other Streptococcus species, and histoplasma.⁵

The majority (77%) of S. aureus isolates were methicillin-resistant S. aureus (MRSA), with 23% methicillin-susceptible S. aureus (MSSA).

Viruses were more frequent in children <5 years of age than older children: RSV (37% vs. 8%), adenovirus (15% vs. 3%), hMPV (15% vs. 8%). M. pneumonia was more frequent in children ≥5 years old than in younger children (19% vs. 3%).⁵

After introduction of the heptavalent pneumococcal conjugate vaccine (PC7) in the United States in 2000, there was a 99% decrease in the incidence of vaccine-type invasive pneumococcal infections.⁴⁰ Other pneumococcal serotypes have emerged as the most common cause of invasive disease. The 2010 introduction of the 13-valent pneumococcal vaccine (PCV13) resulted in a further decrease in the incidence of vaccine-type invasive pneumococcal infections.⁴¹ However, S. pneumonia remains the major cause of bacterial CAP in children.⁴¹

Introduction of the H. influenza type b (Hib) conjugate vaccine in the United States produced a 99% decrease in the incidence of invasive Hib infections in children <5 years old.⁴² In the post-vaccination era, non-typeable H. influenza now causes most invasive H. influenza disease in all age groups.⁴²

hMPV has recently been identified as a leading cause of respiratory tract infection, especially in the first few years of life. It has a clinical spectrum similar to RSV, with bronchiolitis occurring in 59%, croup in 18%, asthma exacerbation in 14%, and pneumonia in 8%. It occurs most frequently during the winter. Mean age of infected children is 11.6 months.⁴³ Other viruses that cause pneumonia include parainfluenza viruses, influenza A and B, adenoviruses, and coronaviruses.⁴¹ The most recently described respiratory virus is HBoV (bocavirus). It is usually found with other viral pathogens. Its’ role as a sole pathogen causing pneumonia is unclear.⁴¹

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