Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis

Debra L. Weiner, Nathan Kuppermann, Richard A. Saladino, Claudette M. Thompson, Thomas J. Novitsky, George R. Siber, Gary R. Fleisher

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: To test the efficacy of a recombinant endotoxin neutralizing protein as compared with saline in rats with Escherichia coli sepsis. Design: Prospective, controlled animal trial. Setting: Hospital animal research laboratory. Subjects: Male Wistar rats challenged with intraperitoneal E. coli, O18ac K1, and treated 1 hr later with ceftriaxone and gentamicin. Interventions: Recombinant endotoxin neutralizing protein, 50 mg/kg, was administered to rats 1, 2, or 3 hrs after E. coli challenge; saline was administered to control animals. Measurements and Main Results: Quantitative bacteremia, 1 hr after challenge and before antibiotic administration, was not significantly different between treatment groups (range geometric mean 451 to 621 colony-forming units [cfu]/mL). The endotoxin concentration, measured immediately before recombinant endotoxin neutralizing protein administration, was significantly higher in animals sampled and treated at 2 hrs (geometric mean 260 EU/mL; 95% confidence interval 140 to 480 EU/mL), or 3 hrs (geometric mean 697 EU/mL; 95% confidence interval 307 to 1585 EU/mL) after E. coli challenge, compared with animals sampled and treated at 1 hr (geometric mean 17 EU/mL; 95% confidence interval 7 to 69 EU/mL). Survival rate was significantly greater in rats treated with recombinant endotoxin neutralizing protein at 1 hr (23/27; p < .001) or 2 hrs (8/30; p < .01) after E. coli challenge than in controls (1/32). Conclusion: Administration of recombinant endotoxin neutralizing protein delayed up to 2 hrs after challenge with E. coli improves survival in antibiotic-treated rats with Gram-negative sepsis.

Original languageEnglish (US)
Pages (from-to)1514-1517
Number of pages4
JournalCritical Care Medicine
Volume24
Issue number9
StatePublished - Sep 1996

Fingerprint

Endotoxins
Sepsis
Escherichia coli
Proteins
Confidence Intervals
Anti-Bacterial Agents
Ceftriaxone
Bacteremia
Gentamicins
Wistar Rats
Stem Cells

Keywords

  • animal model
  • bacterial infection
  • critical illness
  • endotoxin
  • endotoxin neutralizing protein
  • Escherichia coli
  • Gram-negative bacteria
  • sepsis
  • shock
  • treatment

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Weiner, D. L., Kuppermann, N., Saladino, R. A., Thompson, C. M., Novitsky, T. J., Siber, G. R., & Fleisher, G. R. (1996). Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis. Critical Care Medicine, 24(9), 1514-1517.

Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis. / Weiner, Debra L.; Kuppermann, Nathan; Saladino, Richard A.; Thompson, Claudette M.; Novitsky, Thomas J.; Siber, George R.; Fleisher, Gary R.

In: Critical Care Medicine, Vol. 24, No. 9, 09.1996, p. 1514-1517.

Research output: Contribution to journalArticle

Weiner, DL, Kuppermann, N, Saladino, RA, Thompson, CM, Novitsky, TJ, Siber, GR & Fleisher, GR 1996, 'Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis', Critical Care Medicine, vol. 24, no. 9, pp. 1514-1517.
Weiner, Debra L. ; Kuppermann, Nathan ; Saladino, Richard A. ; Thompson, Claudette M. ; Novitsky, Thomas J. ; Siber, George R. ; Fleisher, Gary R. / Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis. In: Critical Care Medicine. 1996 ; Vol. 24, No. 9. pp. 1514-1517.
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abstract = "Objective: To test the efficacy of a recombinant endotoxin neutralizing protein as compared with saline in rats with Escherichia coli sepsis. Design: Prospective, controlled animal trial. Setting: Hospital animal research laboratory. Subjects: Male Wistar rats challenged with intraperitoneal E. coli, O18ac K1, and treated 1 hr later with ceftriaxone and gentamicin. Interventions: Recombinant endotoxin neutralizing protein, 50 mg/kg, was administered to rats 1, 2, or 3 hrs after E. coli challenge; saline was administered to control animals. Measurements and Main Results: Quantitative bacteremia, 1 hr after challenge and before antibiotic administration, was not significantly different between treatment groups (range geometric mean 451 to 621 colony-forming units [cfu]/mL). The endotoxin concentration, measured immediately before recombinant endotoxin neutralizing protein administration, was significantly higher in animals sampled and treated at 2 hrs (geometric mean 260 EU/mL; 95{\%} confidence interval 140 to 480 EU/mL), or 3 hrs (geometric mean 697 EU/mL; 95{\%} confidence interval 307 to 1585 EU/mL) after E. coli challenge, compared with animals sampled and treated at 1 hr (geometric mean 17 EU/mL; 95{\%} confidence interval 7 to 69 EU/mL). Survival rate was significantly greater in rats treated with recombinant endotoxin neutralizing protein at 1 hr (23/27; p < .001) or 2 hrs (8/30; p < .01) after E. coli challenge than in controls (1/32). Conclusion: Administration of recombinant endotoxin neutralizing protein delayed up to 2 hrs after challenge with E. coli improves survival in antibiotic-treated rats with Gram-negative sepsis.",
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