Etiology and Pathogenesis

Epidemiology

Definitions of pneumonia vary: the World Health Organization (WHO) uses the clinical symptoms of cough and fast or difficult breathing to define pneumonia, characterizing a respiratory rate greater than 50 breaths/min for children 2 to 12 months old and greater than 40 breaths/min for children 1 to 5 years old as abnormally fast. In the developed world, pneumonia is commonly defined as the presence of fever (temperature >38.0°C) and signs of lower respiratory tract infection (e.g., cough, tachypnea, hypoxia) with or without abnormalities on chest radiograph.

The annual incidence of pneumonia is greatest among children younger than 1 year old and decreases as children age. CAP causes almost 20% of deaths in children younger than 5 years old in the developing world, but fewer than 1% of children hospitalized with pneumonia in the United States die. CAP nonetheless remains a frequent cause of outpatient pediatric visits and hospitalization. Bacterial pneumonia may be complicated by parapneumonic effusion; the term empyema is used to describe purulent effusions. Empyema occurs in approximately 10% of children hospitalized with CAP.

The common causes of CAP in healthy children in the developed world vary by age group, although an extensive number of pathogens can cause CAP (Table 91-1). Respiratory viruses such as respiratory syncytial virus (RSV); influenza A and B; parainfluenza 1, 2, and 3; adenovirus; and human metapneumovirus (hMPV) can be identified in up to half of patients admitted to the hospital for CAP. These viral pathogens may be identified alone or as part of a co-infection with bacteria. First described in 2001, hMPV, similar to RSV infection in young children, causes a spectrum of respiratory disease ranging from mild bronchiolitis to severe pneumonia.

Table 91-1 Common Bacterial and Viral Causes of Community-Acquired Pneumonia by Age in Healthy Children in the Developed World

≤3 Months Old	3 Months to 5 Years Old	≥5 Years Old
*Bacteria*	*Bacteria*	*Bacteria*
Group B streptococcus	Streptococcus pneumoniae	Streptococcus pneumoniae
Enteric gram-negative bacilli	Mycoplasma pneumoniae	Mycoplasma pneumoniae
Streptococcus pneumoniae	Chlamydophila pneumoniae*	Chlamydophila pneumoniae*
Bordetella pertussis	Staphylococcus aureus	Staphylococcus aureus
Chlamydia trachomatis Staphylococcus aureus	Haemophilus influenzae (nontypable)
*Lower Respiratory Viruses*	*Lower Respiratory Viruses*	*Lower Respiratory Viruses*
Respiratory syncytial virus	Respiratory syncytial virus	Influenza A and B
Influenza A and B	Influenza A and B
Parainfluenza viruses 1, 2, 3	Parainfluenza viruses 1, 2, 3
Human metapneumovirus	Human metapneumovirus
Rhinovirus	Rhinovirus
Adenovirus	Adenovirus
Bocavirus	Bocavirus
Coronaviruses	Coronaviruses

* Formerly Chlamydia pneumoniae.

Streptococcus pneumoniae is the most common bacterial cause of childhood CAP (Figure 91-1). Randomized trials of the heptavalent pneumococcal conjugate vaccine (PCV7) demonstrated that the incidence of radiographically confirmed pneumonia was reduced by 20% in vaccine recipients compared with placebo recipients, suggesting that S. pneumoniae causes at least 20% of CAP cases. Postlicensure epidemiologic studies have shown a 39% decrease in all-cause pneumonia hospitalizations in children younger than 2 years of age but nonsignificant decreases in older children. Thus, the significant role of pneumococcus as a cause of childhood CAP drives the choice of empiric antibiotic therapy for younger children.

Figure 91-1 Pneumococcal pneumonia.

Staphylococcus aureus, particularly community-associated methicillin-resistant S. aureus (CA-MRSA), has been recognized with increasing frequency as a cause of severe CAP even in previously healthy children without exposure to health care settings. Mycoplasma pneumoniae, although previously described as a pathogen limited to adolescents and young adults, is also a common pathogen in school-age children and toddlers. M. pneumoniae has been associated with wheezing, identified in one study in half of patients with a first episode of wheezing and 20% of patients admitted for an exacerbation of their known prior asthma.

Less common causes of CAP include Streptococcus pyogenes, nontypable Haemophilus influenzae, enteric gram-negative pathogens (in cases of aspiration or neurologic compromise), Mycobacterium tuberculosis, herpes simplex virus (in newborns), varicella-zoster virus, Legionella pneumophila, and endemic mycoses such as Histoplasma capsulatum, Coccidioides immitis, and Blastomyces dermatitidis. Before the introduction of the conjugate H. influenzae type b (Hib) vaccine, Hib was a common cause of CAP. In countries and areas where Hib vaccine uptake is low, Hib should still be considered as a common cause of CAP.

Bacterial tracheitis is a serious respiratory infection encountered only rarely, and it is most frequently caused by S. aureus, although other organisms such as nontypable H. influenzae, Moraxella catarrhalis, and anaerobes have been implicated in its pathogenesis. As with bacterial pneumonias, tracheitis often follows an antecedent viral upper respiratory infection.

Pathogenesis

Viral illness alone, such as influenza, can cause severe and necrotizing pneumonia (Figure 91-2). Preceding viral illness may play a part in the pathogenesis of bacterial pneumonia. One study demonstrated that rates of invasive pneumococcal disease each winter season rose in close association with respiratory viral illness diagnoses (RSV, influenza, and hMPV), suggesting that the respiratory damage caused by viral respiratory illness may allow for subsequent bacterial pneumonia. Such data do not prove the direct causation of invasive bacterial pneumonia as a consequence of viral respiratory infection, however. Likewise, a randomized trial of children receiving a pneumococcal vaccine found fewer admissions for both pneumococcal pneumonia and hMPV pneumonia among vaccine recipients compared with placebo recipients, suggesting that hospitalizations for hMPV may involve co-infection with pneumococcus.