Numerous microbes may cause CAP, including a variety of bacteria, viruses, fungi, and protozoa.

Newer viral pathogens include metapneumoviruses, the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and the SARS-CoV-2 coronavirus. First described in December 2019, SARS-CoV-2 and its associated clinical disease, COVID-19, reached pandemic proportions and are a cause of significant morbidity and mortality. The COVID-19 pandemic has changed the etiologic profile of CAP, and the ultimate role that the SARS-CoV-2 virus will play as a cause of CAP remains to be seen.

Although most CAP cases are caused by relatively few pathogens, an accurate determination of their prevalence is difficult because laboratory testing methods are often insensitive and indirect (Table 1). Separation of potential agents into “typical” bacterial pathogens and “atypical” organisms may be helpful, although both types of pathogens can lead to similar clinical syndromes. The former group includes S. pneumoniae, Haemophilus influenzae, and, in selected patients, Staphylococcus aureus and gram-negative bacilli such as Klebsiella pneumoniae and P. aeruginosa. The “atypical” organisms include Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species as well as respiratory viruses such as influenza, adenoviruses, human metapneumoviruses, respiratory syncytial virus, and coronaviruses. With the increasing use of pneumococcal vaccine, the incidence of pneumococcal pneumonia is decreasing. M. pneumoniae plays more of a role in ambulatory cases, whereas Legionella tends to be associated with more serious cases and can be found in outbreaks, as well. C. pneumoniae now appears to account for <1 % of CAP cases. Viruses are recognized as increasingly important in pneumonia, and polymerase chain reaction (PCR)–based testing indicates their presence in the respiratory tract of 20–30% of healthy adults and in the same percentage of pneumonia patients, including those who are severely ill. The most common are influenza, parainfluenza, and respiratory syncytial viruses. Whether they are true etiologic pathogens, co-pathogens, or simply colonizers cannot always be determined. Atypical organisms cannot be cultured on standard media or seen on Gram stain, but their frequency and importance have significant implications for therapy. They are intrinsically resistant to all β-lactam antibiotics and require treatment with a macrolide, fluoroquinolone, or a tetracycline. In the 10–15% of CAP cases that are polymicrobial, the etiology usually includes a combination of typical and atypical pathogens.

Table1. Microbial Causes of Community-Acquired Pneumonia, by Site of Care

Earlier literature suggested that aspiration pneumonia was caused primarily by anaerobes, with or without aerobic pathogens. A shift, however, has been noted recently: if aspiration pneumonia is acquired in a community or hospital setting, the likely pathogens are those usually associated with CAP or HAP. Anaerobes may still play a role, especially in patients with poor dentition, lung abscess, necrotizing pneumonia, or empyema.

S. aureus pneumonia is known to complicate influenza virus infection. However, methicillin-resistant S. aureus (MRSA) has been reported as a primary etiologic agent of CAP. Although cases caused by MRSA are relatively uncommon, clinicians must be aware of its potentially serious consequences, such as necrotizing pneumonia. Two factors have led to this problem: the spread of MRSA from the hospital setting to the community and the emergence of genetically distinct MRSA strains in the community associated with bacterial toxin pro duction. Community-associated MRSA (CA-MRSA) strains may infect healthy individuals who have had no association with health care.

Despite a careful history, physical examination, and radiographic studies, the causative pathogen is often difficult to predict with certainty, and in more than half of cases, a specific etiology is not determined. Nevertheless, epidemiologic and risk factors may suggest certain pathogens (Table 2).

Table2. Epidemiologic Factors Suggesting Possible Causes of Community-Acquired Pneumonia

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