The term atypical pneumonia was first coined in the early 1950s to describe cases of pneumonia caused by an unknown agent(s) and which appeared clinically different from pneumococcal pneumonia. It was initially characterized by constitutional symptoms, often with upper and lower respiratory tract symptoms and signs, a protracted course with gradual resolution, the lack of typical findings of consolidation on chest radiograph, failure to isolate a pathogen on routine bacteriologic methods, and a lack of response to penicillin therapy. In the 1940s an agent that was believed to be the principal cause was identified as Mycoplasma pneumoniae. Subsequently, other pathogens have been linked with atypical pneumonia because of similar clinical presentation, including a variety of respiratory viruses, Chlamydophila psittaci, Coxiella burnetti, and, more recently, Chlamydophila pneumoniae. Less common etiologic agents associated with atypical pneumonia include Francisella tularensis, Yersinia pestis (plague), and the sin nombre virus (hantavirus pulmonary syndrome), although these agents are often associated with a more acute clinical syndrome. In addition, although presently exceedingly rare, inhalation anthrax is included in part because of the concern for this pathogen as an agent of bioterrorism. Finally, pneumonia caused by Legionella species, albeit often more characteristic of pyogenic pneumonia, is also included because it is not isolated using routine microbiologic methods.
Although the original classification of atypical and typical pneumonia arose from the perception that the clinical presentation of patients was different, recent studies have shown that there is considerable overlap of clinical manifestations of specific causes that does not permit empiric therapeutic decisions to be made solely on this basis.