cefamandole and Systemic-Inflammatory-Response-Syndrome

Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Blood Proteins; Bronchoalveolar Lavage Fluid; Cefamandole; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Interleukin-6; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Recombinant Proteins; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha