A comparison of bactericidal/permeability-increasing protein variant versus 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.


METHODS
Randomized, blinded, controlled study, using a rat model of sepsis.


METHODS
Animal research facility.


METHODS
Male Wistar rats.


METHODS
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 95% 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.


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/permeability-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.
Stack
A M
AM
Division of Emergency Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Saladino
R A
RA
Siber
G R
GR
Thompson
C
C
Marra
M N
MN
Novitsky
T J
TJ
Fleisher
G R
GR
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000401:mortality / Q000628:therapy*; D005839:Gentamicins / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D018805:Sepsis / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis
D000890:Anti-Infective Agents; D005839:Gentamicins; D011994:Recombinant Proteins; D002443:Ceftriaxone