Efficacy of Macrolide Immunomodulation in Severe Sepsis.

In recent studies, the significant effects of macrolide antibiotics (azithromycin) on immune response, unrelated to their anti-microbial properties, have been appreciated. Clinical trials of macrolides added to -lactams in bacteremic Streptococcus pneumoniae community-acquired pneumonia (CAP) have consistently demonstrated an absolute risk reduction in mortality of 15% in most populations. Several cytokines including tumor necrosis factor (TNF) interleukin (IL) -1 and IL-8 which are generally proinflammatory and IL-6 and IL-10, which tend to be anti-inflammatory have been associated with sepsis. TNF is a cytokine that for a number of reasons is thought to play a central role in the pathogenesis of sepsis and septic shock. TNF concentrations are increased during clinical and experimental sepsis and increasing concentrations and especially persistence of high concentrations of TNF during sepsis are associated with decreased survival. Therefore, our primary aim is to determine whether macrolide treatment of patients with severe sepsis has an advantageous immunomodulatory and clinical effect compared to severe septic patients without macrolide therapy. Our main hypothesis is macrolide use in addition to standard therapy in severe septic patients has an advantageous immunomodulatory and clinical effect compared to patients with severe sepsis not treated with a macrolide.