sk&f-107647 and Escherichia-coli-Infections

SK&F 107647, a novel synthetic low-molecular-weight peptide, has demonstrated potent antiinfective activities in murine models of fungal and viral infection. To determine if the hematoregulatory activities of SK&F 107647 could offer protection over conventional antibiotic therapy or as a single agent in animal models of bacterial sepsis, rats were implanted intraperitoneally with a live bacteria-containing fibrin-thrombin clot. Rats pretreated subcutaneously or orally with SK&F 107647 and then infected with either a gram-negative (Escherichia coli) or a gram-positive (Staphylococcus aureus) bacteria-containing clot demonstrated significantly improved survival over control formulation-treated animals. Treated animals showed increased effector cell activation, measured by CD11b expression on neutrophils and monocytes, and up to 1000-fold reduction in the number of E. coli recovered from blood. Thus, the hematoregulatory activities of SK&F 107647 can increase natural host resistance to infections caused by both gram-negative and gram-positive bacteria.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; Anti-Bacterial Agents; Bacteremia; CD11 Antigens; Dose-Response Relationship, Drug; Escherichia coli Infections; Gentamicins; Injections, Subcutaneous; Lymphocytes; Male; Oligopeptides; Rats; Rats, Inbred F344; Staphylococcal Infections; Survival Rate; Tumor Necrosis Factor-alpha