A COMPARISON OF BACTERICIDAL PERMEABILITY VERSUS INCREASING PROTEIN VARIANT RECOMBINANT ENDOTOXIN-NEUTRALIZING PROTEIN FOR THE TREATMENT OFESCHERICHIA-COLI SEPSIS IN RATS/

Objective: To compare a recombinant bactericidal/permeability-increasi ng protein variant and a recombinant endotoxin-neutralizing protein, D esign: Randomized, blinded, controlled study, using a rat model of sep sis, Setting: Animal research facility, Subjects: Male Wistar rats. In terventions: An inoculum of 1,5 x 10(7) to 1,8 x 10(8) Escherichia col i O18ac K1, implanted in the peritoneum, produced bacteremia in 95K of animals after 1 hr, One hour after E. coli challenge, animals receive d recombinant bactericidal/permeability-increasing protein variant, re combinant endotoxin-neutralizing protein, or saline intravenously, fol lowed 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/peermeabilit y-increasing protein variant-treated (p <.001 vs, control) and two (6. 5%) of 31 control animals. Conclusions: Both recombinant endotoxin-neu tralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival, Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability increas ing protein variant in its protective effect at the doses tested, Our results suggest that both proteins may be useful in the treatment of h uman Gram-negative sepsis.