Community-acquired pneumonia : pathogenesis of acute cardiac events and potential adjunctive therapies

Abstract

Despite advances in antimicrobial chemotherapy and access to sophisticated intensive care facilities, bacterial community-acquired pneumonia (CAP) continues to carry an unacceptably high mortality rate of 10% to 15% in hospitalized cases. CAP, considered by many to be the most underestimated disease worldwide, poses a particular threat to the elderly whose numbers are steadily increasing in developed countries. Indeed, elderly patients with severe CAP, as well as those with other risk factors, are at significant risk for development of inflammation-mediated acute cardiac events that may undermine the success of antimicrobial therapy. Adjunctive antiinflammatory strategies are, therefore, of considerable potential benefit in this setting. Currently, the most promising of these are the macrolides, corticosteroids, and, more recently, statins, all of which target immune/inflammatory cells. In addition, recent insights into the immunopathogenesis of acute coronary events in patients with CAP have revealed a probable pivotal role of platelet activation, potentially modifiable by agents that possess antiinflammatory or platelet-targeted activities or both. Statins, which not only possess antiinflammatory activity but also appear to target several pathways involved in platelet activation, seem particularly well suited as adjuncts to antibiotic therapy in bacterial CAP. Following a brief consideration of the immunopathogenesis of bacterial CAP, this review is focused on mechanisms of platelet activation by CAP pathogens, as well as the pharmacologic control thereof, with emphasis on statins.