Etiology

Streptococcus pneumoniae (the pneumococcus) is the most common causative bacterial pathogen of community-acquired pneumonia (CAP) across a range of severities and patient ages.[8][9][10][11][12][13]​​​​​ In the US, S pneumoniae is estimated to account for 10% to 14% of confirmed adult hospitalized CAP cases.[14][15]​​​​ However identification of the cause of CAP can be difficult, with one study of 2488 hospitalized patients identifying a causative pathogen in only 38% of patients with CAP.[3][5]​​​

One recent UK prospective cohort study of adults hospitalized with CAP between 2013 and 2023 found that of the 5186 patients with CAP, 2193 (42.2%) had pneumococcal pneumonia. The proportion of CAP due to pneumococcus increased across all ages between 2013 and 2023 (36.4% to 66.9%, p <0.001). The proportion due to serotype 3 increased significantly from 13.4% (2013) to 48.8% (2023). The study concluded that there is likely a lack of herd immunity for this serotype, despite the childhood immunization program.[16]

The systematic analysis for the Global Burden of Disease Study 2019 found globally the most common bacterial causes of death from lower respiratory infections (and all related infections of the thorax) after S pneumoniae included Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Group B streptococcus, Escherichia coli and Haemophilus influenzae.[13]

Atypical bacteria are also common causes, although they vary in frequency depending on the year and any epidemics.[12][17]​​​ The incidence of atypical pathogens in CAP is approximately 22% globally, but this varies with location.[18] The most commonly reported atypical bacteria are Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. M pneumoniae accounts for up to 5% to 8% of CAP.[19]

C pneumoniae has generally been considered to account for <1.5% of CAP, but more recent sporadic outbreaks have been observed, such as during a 2023 outbreak in Switzerland where the C pneumoniae incidence peaked at 6.66%.[20]​ L pneumophila (especially serogroup 1) accounts for approximately 4.6% of CAP in immunocompetent patients.[21]​

One systematic review found that Chlamydia psittaci was the causative organism in 1% of patients.[22] However, a Dutch study identified C psittaci by polymerase chain reaction (PCR) of sputum (when available) as a cause of CAP in 4.8% of cases.[23]

Approximately 6% of cases are due to PES pathogens (Pseudomonas aeruginosa, extended-spectrum beta-lactamase Enterobacteriaceae, and methicillin-resistant S aureus [MRSA]). Of these organisms, P aeruginosa and MRSA are the most frequently reported.[24][25]

Respiratory viruses are reported in about 10% to 30% of immunocompetent adults hospitalized with CAP.[9][26][27][28]​​​​​ Among the viral pathogens, influenza virus, rhinovirus and SARS-CoV-2 are the most common organisms detected in the US.[29]​ SARS-CoV-2 infection was a major cause of CAP during the pandemic, with data on prevalence continuing to change with emergence of disease variants and patient vaccination status.[30]​ Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in older adults. One US meta-analysis reported pooled annual RSV incidence per 100,000 adults aged 65 and older as 178 hospitalizations, 133 emergency department (ER) visits, and 1,519 outpatient visits.[31]​ One study of 2865 severe pneumonia cases showed lower RSV pneumonia incidence than influenza (3.4% vs. 8.1%), but slightly higher in hospital-acquired pneumonia (3.8% vs. 3.5%).[32]

Viral sepsis has been reported in 3% of all patients admitted to the ER department with a diagnosis of CAP, 19% of all patients with CAP who are admitted to the intensive care unit, and 61% of those with a diagnosis of viral CAP. Males and older patients (age ≥65 years) are at an increased risk for viral sepsis.[33] Newer pathogens reported to cause CAP include metapneumovirus as well as coronavirus and its variants.[34] Detection of viral causes is increasing because of the use of PCR.

Polymicrobial etiology in CAP varies from 5.7% to 13.0%, depending on the population and the microbiological diagnostic test used.[9][27][35]

Pathophysiology

Pneumonia develops subsequent to the invasion and overgrowth of a pathogenic microorganism in the lung parenchyma, which overwhelms host defenses and produces intra-alveolar exudates.[36]

The development and severity of pneumonia is a balance between pathogen factors (virulence, inoculum size) and host factors. The likely microbial causes of CAP differ according to a number of factors, including differences in local epidemiology, the setting (outpatients, hospitalized, or intensive care unit), severity of disease, and patient characteristics (e.g., sex, age, and comorbidities).[9]

Microbes that are present in the upper airways can enter the lower airways by microaspiration. Nevertheless, the defense mechanisms of the lungs (innate and acquired) keep the lower airways sterile. The development of pneumonia indicates a defect in host defenses, exposure to a particularly virulent microorganism, or a large inoculum size.

Impaired immune response (e.g., caused by HIV infection or advanced age) or dysfunction of defense mechanism (e.g., through current or passive smoking, COPD, or aspiration) leads to greater susceptibility to respiratory infections in patients.[37]

Pathogens can reach the lower respiratory tract by 4 mechanisms:

  • Inhalation, a common route of entry for viral and atypical pneumonia in younger healthy patients. Infectious aerosols are inhaled into the respiratory tract of a susceptible person to initiate infection

  • Aspiration of oropharyngeal secretions into the trachea, the primary route through which pathogens enter the lower airways

  • Hematogenous spread from a localized infected site (e.g., right-sided endocarditis)[38]

  • Direct extension from adjacent infected foci (e.g., tuberculosis can spread contiguously from the lymph nodes to the pericardium or the lung, albeit rarely).

Pneumonia may result from dysbiosis of the normal lung flora, rather than invasion of pathogenic microorganisms in a sterile environment.[39] Multiple bacterial species (e.g., Prevotella, Veillonella, Streptococcus, Fusobacterium, and Haemophilus) are present in a healthy lung and are known as the lung microbiome. The upper respiratory tract is the primary source of the lung microbiome. These bacteria are part of a dynamic community where a balance, or equilibrium, is maintained. When disequilibrium (or dysbiosis) occurs, as is the case in acute infections, the microbiome changes. Risk factors for dysbiosis are partially understood, but further study is required.[40][41]

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