Epidemiology

Pneumonia—inflammation of the parenchyma of the lungs—is a substantial cause of morbidity and mortality in childhood throughout the world, rivaling diarrhea as a cause of death in developing countries (Fig. 392-1). With ≈158 million episodes of pneumonia per year, of which ≈154 million are occurring in developing countries, pneumonia is estimated to cause ≈3 million deaths, or an estimated 29% of all deaths, among children younger than 5 yr worldwide. The incidence of pneumonia is more than 10-fold higher (0.29 episodes versus 0.03 episodes), and the number of childhood-related deaths due to pneumonia ≈2000-fold higher, in developing than in developed countries (Table 392-1).

Figure 392-1 Pneumonia is the leading killer of children worldwide, as shown by this illustration of global distribution of cause-specific mortality among children <5 yr in 2004. Pneumonia causes 19% of all under-5 deaths. This illustration, however, does not include deaths due to pneumonia during the neonatal period. It is estimated that 26% of neonatal deaths, or 10% of under-5 deaths, are caused by severe infections. Large proportions of these infections are caused by pneumonia/sepsis. If these deaths were added to the overall estimate, pneumonia would account for up to 3 million, or as many as one third (29%), of under-5 deaths worldwide.

(Sources of data: Cause-specific mortality estimates from WHO. World Health Report 2005: Make Every Mother and Child Count. Geneva: World Health Organization, 2005; under-five mortality estimates from UNICEF. The state of the world’s children 2006. New York: United Nations Children’s Fund, 2005. From Wardlaw T, Salama P, Johansson EW: Pneumonia: the leading killer of children, Lancet 368:1048–1050, 2006.)

In the USA from 1939 to 1996, pneumonia mortality in children declined by 97%. It is hypothesized that this decline is attributable to the introduction of antibiotics, vaccines, and the expansion of medical insurance coverage for children. Haemophilus influenzae type b (Hib) (Chapter 186) was an important cause of bacterial pneumonia in young children but has become uncommon with the routine use of effective vaccines. The introduction of heptavalent pneumococcal conjugate vaccine and its impact on pneumococcal disease (Chapter 175) has reduced the overall incidence of pneumonia in infants and children in the USA by ≈30% in the 1st yr of life, ≈20% in the 2nd yr of life, and ≈10% in children >2 yr of age. In developing countries, the introduction of measles vaccine has greatly reduced the incidence of measles-related pneumonia deaths.

Etiology

Although most cases of pneumonia are caused by microorganisms, noninfectious causes include aspiration of food or gastric acid, foreign bodies, hydrocarbons, and lipoid substances, hypersensitivity reactions, and drug- or radiation-induced pneumonitis. The cause of pneumonia in an individual patient is often difficult to determine because direct culture of lung tissue is invasive and rarely performed. Cultures performed on specimens obtained from the upper respiratory tract or “sputum” often do not accurately reflect the cause of lower respiratory tract infection. With the use of state-of-the-art diagnostic testing, a bacterial or viral cause of pneumonia can be identified in 40-80% of children with community-acquired pneumonia. Streptococcus pneumoniae (pneumococcus) is the most common bacterial pathogen in children 3 wk to 4 yr of age, whereas Mycoplasma pneumoniae and Chlamydophila pneumoniae are the most frequent pathogens in children 5 yr and older. In addition to pneumococcus, other bacterial causes of pneumonia in previously healthy children in the USA include group A streptococcus (Streptococcus pyogenes) and Staphylococcus aureus (Chapter 174.1) (Table 392-2).

Table 392-2 CAUSES OF INFECTIOUS PNEUMONIA

* Atypical pneumonia syndrome; may have extrapulmonary manifestations, low-grade fever, patchy diffuse infiltrates, poor response to beta-lactam antibiotics, and negative sputum Gram stain.

From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis & therapy, ed 2, 2004, Philadelphia, Elsevier, p 29.

S. pneumoniae, H. influenzae, and S. aureus are the major causes of hospitalization and death from bacterial pneumonia among children in developing countries, although in children with HIV infection, Mycobacterium tuberculosis (Chapter 207), atypical mycobacteria, Salmonella (Chapter 190), Escherichia coli (Chapter 192), and Pneumocystis jiroveci (Chapter 236) must be considered. The incidence of H. influenzae has been significantly reduced in areas where routine Hib immunization has been implemented.

Viral pathogens are a prominent cause of lower respiratory tract infections in infants and children <5 yr of age. Viruses are responsible for 45% of the episodes of pneumonia identified in hospitalized children in Dallas. Unlike bronchiolitis, for which the peak incidence is in the 1st yr of life, the highest frequency of viral pneumonia occurs between the ages of 2 and 3 yr, decreasing slowly thereafter. Of the respiratory viruses, influenza virus (Chapter 250), and respiratory syncytial virus (RSV) (Chapter 252) are the major pathogens, especially in children <3 yr of age. Other common viruses causing pneumonia include parainfluenza viruses, adenoviruses, rhinoviruses, and human metapneumovirus. The age of the patient may help identify possible pathogens (Table 392-3).

Table 392-3 ETIOLOGIC AGENTS GROUPED BY AGE OF THE PATIENT

From Kliegman RM, Marcdante KJ, Jenson HJ, et al: Nelson essentials of pediatrics, ed 5, Philadelphia, 2006, Elsevier, p 504.

* H. influenzae type b is uncommon with routine H. influenzae type b immunization.

Lower respiratory tract viral infections in the USA are much more common in the fall and winter, in relation to the seasonal epidemics of respiratory viral infection that occur each year. The typical pattern of these epidemics usually begins in the fall, when parainfluenza infections appear and most often manifest as croup. Later in winter, RSV, human metapneumovirus, and influenza viruses cause widespread infection, including upper respiratory tract infections, bronchiolitis, and pneumonia. RSV attacks infants and young children, whereas influenza virus causes disease and excess hospitalization for acute respiratory illness in all age groups. Knowledge of the prevailing viral epidemic may lead to a presumptive initial diagnosis.

Immunization status is relevant because children fully immunized against H. influenzae type b and S. pneumoniae are less likely to be infected with these pathogens. Children who are immunosuppressed or who have an underlying illness may be at risk for specific pathogens, such as Pseudomonas spp. in patients with cystic fibrosis.

Pathogenesis

The lower respiratory tract is normally kept sterile by physiologic defense mechanisms, including mucociliary clearance, the properties of normal secretions such as secretory immunoglobulin A (IgA), and clearing of the airway by coughing. Immunologic defense mechanisms of the lung that limit invasion by pathogenic organisms include macrophages that are present in alveoli and bronchioles, secretory IgA, and other immunoglobulins. Additional factors that promote pulmonary infection include trauma, anesthesia, and aspiration.

Viral pneumonia usually results from spread of infection along the airways, accompanied by direct injury of the respiratory epithelium, which results in airway obstruction from swelling, abnormal secretions, and cellular debris. The small caliber of airways in young infants makes such patients particularly susceptible to severe infection. Atelectasis, interstitial edema, and ventilation-perfusion mismatch causing significant hypoxemia often accompany airway obstruction. Viral infection of the respiratory tract can also predispose to secondary bacterial infection by disturbing normal host defense mechanisms, altering secretions, and modifying the bacterial flora.

Bacterial pneumonia most often occurs when respiratory tract organisms colonize the trachea and subsequently gain access to the lungs, but pneumonia may also result from direct seeding of lung tissue after bacteremia. When bacterial infection is established in the lung parenchyma, the pathologic process varies according to the invading organism. M. pneumoniae attaches to the respiratory epithelium, inhibits ciliary action, and leads to cellular destruction and an inflammatory response in the submucosa. As the infection progresses, sloughed cellular debris, inflammatory cells, and mucus cause airway obstruction, with spread of infection occurring along the bronchial tree, as it does in viral pneumonia.

S. pneumoniae produces local edema that aids in the proliferation of organisms and their spread into adjacent portions of lung, often resulting in the characteristic focal lobar involvement.

Group A streptococcus infection of the lower respiratory tract results in more diffuse infection with interstitial pneumonia. The pathology includes necrosis of tracheobronchial mucosa; formation of large amounts of exudate, edema, and local hemorrhage, with extension into the interalveolar septa; and involvement of lymphatic vessels and the increased likelihood of pleural involvement.

S. aureus pneumonia manifests in confluent bronchopneumonia, which is often unilateral and characterized by the presence of extensive areas of hemorrhagic necrosis and irregular areas of cavitation of the lung parenchyma, resulting in pneumatoceles, empyema, or, at times, bronchopulmonary fistulas.

Recurrent pneumonia is defined as 2 or more episodes in a single year or 3 or more episodes ever, with radiographic clearing between occurrences. An underlying disorder should be considered if a child experiences recurrent pneumonia (Table 392-4).

From Kliegman RM, Marcdante KJ, Jenson HJ, et al: Nelson essentials of pediatrics, ed 5, Philadelphia, 2006, Elsevier, p 507.

Clinical Manifestations

Viral and bacterial pneumonias are often preceded by several days of symptoms of an upper respiratory tract infection, typically rhinitis and cough. In viral pneumonia, fever is usually present; temperatures are generally lower than in bacterial pneumonia. Tachypnea is the most consistent clinical manifestation of pneumonia. Increased work of breathing accompanied by intercostal, subcostal, and suprasternal retractions, nasal flaring, and use of accessory muscles is common. Severe infection may be accompanied by cyanosis and respiratory fatigue, especially in infants. Auscultation of the chest may reveal crackles and wheezing, but it is often difficult to localize the source of these adventitious sounds in very young children with hyperresonant chests. It is often not possible to distinguish viral pneumonia clinically from disease caused by Mycoplasma and other bacterial pathogens.

Bacterial pneumonia in adults and older children typically begins suddenly with a shaking chill followed by a high fever, cough, and chest pain. Other symptoms that may be seen include drowsiness with intermittent periods of restlessness; rapid respirations; anxiety; and, occasionally, delirium. Circumoral cyanosis may be observed. In many children, splinting on the affected side to minimize pleuritic pain and improve ventilation is noted; such children may lie on one side with the knees drawn up to the chest.

Physical findings depend on the stage of pneumonia. Early in the course of illness, diminished breath sounds, scattered crackles, and rhonchi are commonly heard over the affected lung field. With the development of increasing consolidation or complications of pneumonia such as effusion, empyema, and pyopneumothorax, dullness on percussion is noted and breath sounds may be diminished. A lag in respiratory excursion often occurs on the affected side. Abdominal distention may be prominent because of gastric dilation from swallowed air or ileus. Abdominal pain is common in lower lobe pneumonia. The liver may seem enlarged because of downward displacement of the diaphragm secondary to hyperinflation of the lungs or superimposed congestive heart failure.

Symptoms described in adults with pneumococcal pneumonia may be noted in older children but are rarely observed in infants and young children, in whom the clinical pattern is considerably more variable. In infants, there may be a prodrome of upper respiratory tract infection and diminished appetite, leading to the abrupt onset of fever, restlessness, apprehension, and respiratory distress. These infants appear ill, with respiratory distress manifested as grunting; nasal flaring; retractions of the supraclavicular, intercostal, and subcostal areas; tachypnea; tachycardia; air hunger; and often cyanosis. Results of physical examination may be misleading, particularly in young infants, with meager findings disproportionate to the degree of tachypnea. Some infants with bacterial pneumonia may have associated gastrointestinal disturbances characterized by vomiting, anorexia, diarrhea, and abdominal distention secondary to a paralytic ileus. Rapid progression of symptoms is characteristic in the most severe cases of bacterial pneumonia.

Diagnosis

An infiltrate on chest radiograph supports the diagnosis of pneumonia; the film may also indicate a complication such as a pleural effusion or empyema. Viral pneumonia is usually characterized by hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing (Fig. 392-2). Confluent lobar consolidation is typically seen with pneumococcal pneumonia (Fig. 392-3). The radiographic appearance alone is not diagnostic, and other clinical features must be considered. Repeat chest radiographs are not required for proof of cure for patients with uncomplicated pneumonia.

Figure 392-2 A, Radiographic findings characteristic of respiratory syncytial virus pneumonia in a 6 mo old infant with rapid respirations and fever. Anteroposterior radiograph of the chest shows hyperexpansion of the lungs with bilateral fine air space disease and streaks of density, indicating the presence of both pneumonia and atelectasis. An endotracheal tube is in place. B, One day later, the AP radiograph of the chest shows increased bilateral pneumonia.

Figure 392-3 Radiographic findings characteristic of pneumococcal pneumonia in a 14 yr old boy with cough and fever. Posteroanterior (A) and lateral (B) chest radiographs reveal consolidation in the right lower lobe, strongly suggesting bacterial pneumonia.

The peripheral white blood cell (WBC) count can be useful in differentiating viral from bacterial pneumonia. In viral pneumonia, the WBC count can be normal or elevated but is usually not higher than 20,000/mm³, with a lymphocyte predominance. Bacterial pneumonia is often associated with an elevated WBC count, in the range of 15,000-40,000/mm³, and a predominance of granulocytes. A large pleural effusion, lobar consolidation, and a high fever at the onset of the illness are also suggestive of a bacterial etiology. Atypical pneumonia due to C. pneumoniae or M. pneumoniae is difficult to distinguish from pneumococcal pneumonia on the basis of radiographic and laboratory findings, and although pneumococcal pneumonia is associated with a higher WBC count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level, there is considerable overlap.

The definitive diagnosis of a viral infection rests on the isolation of a virus or detection of the viral genome or antigen in respiratory tract secretions. Growth of respiratory viruses in conventional viral culture usually requires 5-10 days, although shell vial cultures can reduce this “turnaround time” to 2-3 days. Reliable DNA or RNA tests for the rapid detection of RSV, parainfluenza, influenza, and adenoviruses are available and accurate. Serologic techniques can also be used to diagnose a recent respiratory viral infection but generally require testing of acute and convalescent serum samples for a rise in antibodies to a specific viral agent. This diagnostic technique is laborious, slow, and not generally clinically useful because the infection usually resolves by the time it is confirmed serologically. Serologic testing may be valuable as an epidemiologic tool to define the incidence and prevalence of the various respiratory viral pathogens.

The definitive diagnosis of a bacterial infection requires isolation of an organism from the blood, pleural fluid, or lung. Culture of sputum is of little value in the diagnosis of pneumonia in young children. Blood culture results are positive in only 10% of children with pneumococcal pneumonia. Cold agglutinins at titers >1 : 64 are found in the blood in ≈50% of patients with M. pneumoniae infections. Cold agglutinin findings are nonspecific because other pathogens such as influenza viruses may also cause increases. Acute infection caused by M. pneumoniae can be diagnosed on the basis of a positive polymerase chain reaction (PCR) test result or seroconversion in an IgG assay. Serologic evidence, such as the antistreptolysin O (ASO) titer, may be useful in the diagnosis of group A streptococcal pneumonia.

Treatment

Treatment of suspected bacterial pneumonia is based on the presumptive cause and the age and clinical appearance of the child. For mildly ill children who do not require hospitalization, amoxicillin is recommended. In communities with a high percentage of penicillin-resistant pneumococci, high doses of amoxicillin (80-90 mg/kg/24 hr) should be prescribed. Therapeutic alternatives include cefuroxime axetil and amoxicillin/clavulanate. For school-aged children and in children in whom infection with M. pneumoniae or C. pneumoniae is suggested, a macrolide antibiotic such as azithromycin is an appropriate choice. In adolescents, a respiratory fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin) may be considered as an alternative. In developing countries only ≈54% of children with pneumonia (≈41% in sub-Saharan Africa) are taken to an appropriate caregiver. In response, the World Health Organization and other international groups have developed systems to train mothers and local health care providers in the recognition and treatment of pneumonia.

The empiric treatment of suspected bacterial pneumonia in a hospitalized child requires an approach based on the clinical manifestations at the time of presentation. Parenteral cefotaxime or ceftriaxone is the mainstay of therapy when bacterial pneumonia is suggested. If clinical features suggest staphylococcal pneumonia (pneumatoceles, empyema), initial antimicrobial therapy should also include vancomycin or clindamycin.

If viral pneumonia is suspected, it is reasonable to withhold antibiotic therapy, especially for those patients who are mildly ill, have clinical evidence suggesting viral infection, and are in no respiratory distress. Up to 30% of patients with known viral infection may have coexisting bacterial pathogens. Therefore, if the decision is made to withhold antibiotic therapy on the basis of presumptive diagnosis of a viral infection, deterioration in clinical status should signal the possibility of superimposed bacterial infection, and antibiotic therapy should be initiated.

Indications for admission to a hospital are noted in Table 392-5. In developing countries, oral zinc (20 mg/day) helps accelerate recovery from severe pneumonia. The optimal duration of antibiotic treatment for pneumonia has not been well-established in controlled studies. For pneumococcal pneumonia, antibiotics should probably be continued until the patient has been afebrile for 72 hours, and the total duration should not be less than 10 to 14 days (or 5 days if azithromycin is used). Available data do not support prolonged courses of treatment for uncomplicated pneumonia.

Prognosis

Typically, patients with uncomplicated community-acquired bacterial pneumonia show response to therapy, with improvement in clinical symptoms (fever, cough, tachypnea, chest pain), within 48-96 hr of initiation of antibiotics. Radiographic evidence of improvement lags substantially behind clinical improvement. A number of factors must be considered when a patient does not improve with appropriate antibiotic therapy: (1) complications, such as empyema; (2) bacterial resistance; (3) nonbacterial etiologies such as viruses and aspiration of foreign bodies or food; (4) bronchial obstruction from endobronchial lesions, foreign body, or mucous plugs; (5) pre-existing diseases such as immunodeficiencies, ciliary dyskinesia, cystic fibrosis, pulmonary sequestration, or cystic adenomatoid malformation; and (6) other noninfectious causes (including bronchiolitis obliterans, hypersensitivity pneumonitis, eosinophilic pneumonia, aspiration, and Wegener’s granulomatosis). A repeat chest radiograph is the 1st step in determining the reason for delay in response to treatment.

Mortality from community-acquired pneumonia in developed nations is rare, and most children with pneumonia do not experience long-term pulmonary sequelae. Some data suggest that up to 45% of children have symptoms of asthma 5 yr after hospitalization for pneumonia; this finding may reflect either undiagnosed asthma at the time of presentation or a propensity for development of asthma after pneumonia.

Complications

Complications of pneumonia are usually the result of direct spread of bacterial infection within the thoracic cavity (pleural effusion, empyema, pericarditis) or bacteremia and hematologic spread (Fig. 392-4). Meningitis, suppurative arthritis, and osteomyelitis are rare complications of hematologic spread of pneumococcal or H. influenzae type b infection.

Figure 392-4 Pneumococcal empyema on the chest radiography of a 3 yr old child who has had upper respiratory symptoms and fever for 3 days. A pleural fluid collection can be seen on the right side. The patient had a positive pleural tap and blood culture result for pneumococci. The child recovered completely within 3 wk.

(From Kuhn JP, Slovis TL, Haller JO: Caffrey’s pediatric diagnostic imaging, vol 1, ed 10, Philadelphia, 2004, Mosby/Elsevier, p 1002.)

S. aureus, S. pneumoniae, and S. pyogenes are the most common causes of parapneumonic effusions and of empyema (Table 392-6). The treatment of empyema is based on the stage (exudative, fibrinopurulent, organizing). Imaging studies including ultrasonography and CT are helpful in determining the stage of empyema. The mainstays of therapy include antibiotic therapy and drainage with tube thoracostomy. Additional approaches include the use of intrapleural fibrinolytic therapy (urokinase, streptokinase, tissue plasminogen activator) and selected video-assisted thoracoscopy (VATS) to debride or lyse adhesions, and drain loculated areas of pus. Early diagnosis and intervention, particularly with fibrinolysis or VATS, may obviate the need for thoracotomy and open debridement. Fibrinolysis may be more cost effective than VATS.

Table 392-6 DIFFERENTIATION OF PLEURAL FLUID

* Low glucose or pH may be seen in malignant effusion, tuberculosis, esophageal rupture, pancreatitis (positive pleural amylase), and rheumatologic diseases (e.g., systemic lupus erythematosus).

From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis & therapy, ed 2, Philadelphia, 2004, Elsevier, p 30.

Prevention

Some evidence exists to suggest that vaccination has reduced the incidence of pneumonia hospitalizations. The annual rate of all-cause pneumonia hospitalization among children <2 yr of age in the USA during the period 1997-1999 was 12.5 per 1000 children. In February 2000 the 7-valent pneumococcal conjugate vaccine (PCV7) was licensed and recommended. In 2006 the pneumonia hospitalization rate in this age group was 8.1 per 1,000 children, a 35% decrease from the pre-vaccine rate. Although these data do not establish that PCV7 directly reduced pneumonia hospitalization rates, they do suggest that vaccination has resulted in a sustained benefit in preventing hospitalization for young children with pneumonia.

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is licensed; it may prevent even more cases of pneumococcal disease not covered by the PCV7 vaccine.

The expansion of influenza vaccine recommendations to include all children >6 mo of age might be expected to affect pneumonia hospitalization rates in a similar fashion, and ongoing surveillance is warranted.