A comparison of bactericidal/permeability versus increasing protein variant recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli sepsis in rats

Objective: To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein, Design: Randomized, blinded, controlled study, using a rat model of sepsis, Setting: Animal research facility, Subjects: Male Wistar rats. Interventions: An inoculum of 1,5 x 10(7) to 1,8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95K of animals after 1 hr, One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly, Measurements and Main Results: Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs, control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/peermeability-increasing protein variant-treated (p <.001 vs, control) and two (6.5%) of 31 control animals. Conclusions: Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival, Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability increasing protein variant in its protective effect at the doses tested, Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.