Is Activity against “Atypical” Pathogens Necessary in the Treatment Protocols for Community‐Acquired Pneumonia? Issues with Combination Therapy

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Abstract
The “atypical pathogens” reviewed include Legionella pneumophila, Chlamydophilia pneumoniae, and Mycoplasma pneumoniae. Urinary antigen tests are the most frequently used tests for Legionella species and show good specificity and reasonable sensitivity. For M. pneumoniae, detection of immunoglobulin M, used for the past decade, has substantially improved diagnostic specificity and has simplified testing. For C. pneumoniae, there is no consensus on a simplified test that can be commonly used, and the reported results, with the use of tests that have not been well validated for diagnostic accuracy, show great variation in prevalence. With regard to therapeutic trials, 3 meta-analyses have recently addressed the issue of clinical outcome with or without antibiotics directed against atypical pathogens (macrolides or fluoroquinolones vs. β-lactam agents). These analyses have not been able to demonstrate any clinical benefit, except in a subset analysis of infections caused by L. pneumophila. Nevertheless, multiple studies from the 1950s and 1960s supported a clinical benefit of tetracycline or erythromycin treatment for infections caused by M. pneumoniae. The largest uncontrolled review of antibiotic treatment for hospitalized patients with community-acquired pneumonia demonstrated a clear benefit from the use of macrolides plus cephalosporins or fluoroquinolones, compared with the use of β-lactams alone, although these data support a potential role for atypical agents, because other potential explanations make drawing conclusions difficult. With regard to future studies, it is noted that the standard of care in the United States, Canada, and some other countries is routine use of agents to treat infection with atypical pathogens, which makes the conduct of controlled trials to address these issues ethically difficult and practically impossible. Additional limitations are the difficulty in diagnostic testing for C. pneumoniae and the importance of rapid institution of therapy for patients severely ill enough to require hospitalization. These observations introduce substantial ethical and logistical barriers to studies of specific agents, except by retrospective analyses.

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