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A study of the interaction between recombinant bactericidal permeability increasing protein (rBPI(23)) and gentamicin

N J Saunders1, J Cohen

  • 1Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

International Journal of Antimicrobial Agents
|July 1, 1995
PubMed

Insights

Recombinant bactericidal permeability increasing protein (rBPI(23)) showed additive or synergistic effects when combined with gentamicin against Gram-negative organisms. These interactions were strongest in bacteria most susceptible to rBPI(23) alone.

Area of Science:

  • Microbiology
  • Pharmacology
  • Immunology

Background:

  • Bactericidal permeability increasing protein (BPI) is a host defense protein with potent antibacterial and endotoxin-neutralizing activities.
  • Recombinant BPI (rBPI(23)) is a therapeutic candidate for Gram-negative sepsis, having completed Phase 1 clinical trials.
  • Gentamicin is a common antibiotic used in treating Gram-negative bacterial infections.

Purpose of the Study:

  • To investigate the in vitro interaction between rBPI(23) and gentamicin.
  • To determine if combining rBPI(23) with gentamicin results in additive or synergistic antibacterial effects.
  • To assess how the inherent susceptibility of Gram-negative organisms to rBPI(23) influences this interaction.

Main Methods:

  • Broth microdilution chequerboard method was employed.
  • A panel of Gram-negative organisms with varying susceptibilities to rBPI(23) was utilized.
  • Fractional Inhibitory Concentration (FIC) indices were calculated to assess drug interactions.

Main Results:

  • Additive or synergistic effects were observed when rBPI(23) was combined with gentamicin.
  • The degree of synergy or additivity was generally proportional to the organism's baseline susceptibility to rBPI(23).
  • No antagonistic interactions were noted.

Conclusions:

  • Combination therapy with rBPI(23) and gentamicin shows potential for enhanced efficacy against Gram-negative infections.
  • rBPI(23) may potentiate the activity of conventional antibiotics like gentamicin.
  • Further clinical investigation is warranted to explore the therapeutic benefits of this combination in sepsis management.

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