The first step is to evaluate the pneumonia patient with detailed history and physical examination. The diagnosis may be made clinically in the appropriate setting, although blood counts, blood biochemistry, and chest x-ray are usually performed as well. In more severe illness, especially when admission is needed and in order to identify a possible typical bacterial pathogen, cultures of blood and sputum may be required, as well as specific cultures and urine antigen tests for Legionella and Streptococcus pneumoniae.[17] Some authors even advocate the use of specific tests for the identification of atypical bacterial and viral pathogens in such settings to guide specific targeted therapy.[31] In some cases (up to 25%) mixed infections can be identified.[3] If available, virological diagnostics should be performed to guide possible treatment for influenza.

History and clinical examination

Key risk factors include close community settings (e.g., boarding schools, college dormitories, army basic training camps, or even hospitals)[4][29] and immunosuppression. A history of exposure to someone with respiratory infection is also a risk factor for atypical bacterial pneumonia. Many patients with atypical bacterial pneumonia are younger than 50 years.

Typically, patients complain about a persistent cough that does not resolve with time. The presence of a dry cough and a prolonged time from onset of symptoms to the presentation should prompt suspicion that an atypical pathogen is present. Fever, if present, is usually low grade. In many cases of Mycoplasma pneumoniae and Chlamydophila pneumoniae, pharyngitis, hoarseness, and headache may also be present. Diarrhoea may accompany Legionella infections. Bullous myringitis is rare sign that suggests M pneumoniae infection. Rash, mainly a self-limited maculopapular or vesicular rash can accompany M pneumoniae pneumonia. In some cases, a more severe form of Stevens-Johnson syndrome affecting the oral mucosa or other parts can be seen.

Clinical signs of pneumonia such as rales/crepitations may be mild or absent.

Suspected atypical pathogen

Treatment guidelines for managing patients with community-acquired pneumonia are designed to cover atypical pathogens.[17] Nonetheless, it is best to confirm the diagnosis if an atypical pathogen is suspected because this may have implications for duration of therapy.

The chest x-ray confirms infiltrates and may show more extensive abnormalities than physical examination suggests. A low oxygen saturation indicates a more severe course of disease requiring hospitalisation.

A white blood cell (WBC) count should be done for patients requiring hospitalisation. Relatively minor elevations in WBC counts are seen (usually <13,000 x 10⁹/L [<13,000/microlitre]). A relative lymphocytosis is observed if infection is viral. A low haemoglobin count may accompany M pneumoniae infections. Elevated liver enzymes suggest M pneumoniae or Legionella pneumophila. Liver function tests should be ordered in hospitalised patients. An elevation in urea level (70.7 mmol/L; >198 mg/dL) suggests more severe disease.

Molecular-based diagnostic tests for M pneumoniae from throat swabs are now available in many formats, including in-house and commercial assays. Molecular-based diagnostics for C pneumoniae are available, either from sputum or throat swabs. However, lack of standardisation between many of the tests may affect the rate of diagnosis and validity.[32] A study from the Netherlands has raised concerns over the interpretation of positive polymerase chain reaction results in patients younger than 16 years because of the high carriage rate of M pneumoniae in the upper respiratory tracts of healthy children.[33] But another study from the US failed to support this observation.[3] New, validated tests that are becoming commercially available may facilitate an increased understanding of the aetiology of atypical pneumonia.[34]

Serology for both M pneumoniae and C pneumoniae may also be conducted, although such tests will not influence treatment, given that the diagnosis will be confirmed retrospectively, based on convalescent serology. It requires blood from early in the course of disease and a second blood specimen at least 10 days later. Lack of standardisation between many of the tests might affect also rate of diagnosis. It may also be used to confirm diagnosis of many atypical pathogens and some viruses. In most cases, serology will be the main diagnostic test for Coxiella burnetii pneumonia.[35]

Where there is uncertainty regarding whether patients with community-acquired pneumonia have typical or atypical pathogen disease, they should undergo a sputum Gram stain and culture. Urine for a Legionella antigen test may also be sent.[17] Nasopharyngeal viral cultures may be difficult to culture and results may take many days to return. However, molecular diagnostics on nasopharyngeal viral swabs are widely available.

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