Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the eighth overall leading cause of death in the United States. For this reason, adjunctive therapeutic measures directed at the host response rather than the pathogen are attractive. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. The existing literature does not demonstrate a clear benefit for corticosteroids, but larger prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome positively. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, but neither drotrecogin alfa activated nor tifacogin (recombinant tissue factor pathway inhibitor) have demonstrated a survival benefit. Other therapies have theoretical benefit but are not yet in the stage of clinical trials.
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