The tyrosine kinase inhibitor AG556 reduces serum tumor necrosis factor levels and tissue injury and improves survival in both small and large animal models of gram-negative infection and sepsis. No data are presently available regarding the effects of AG556 during gram-positive infection. We, therefore, investigated this agent in rats challenged with S. aureus. In these studies we found that AG556 was not beneficial with gram-positive infection. We have continued these studies to determine whether AG556 would be beneficial during gram-positive infection in a canine model of peritonitis that utilizes antibiotics and fluid support. In a similar model, we had shown that AG556 clearly improved survival with gram-negative infection. We have now studied the effects of AG556 with two differing doses of S. aureus and are analyzing and comparing data from both the S. aureus and E. coli studies.
