Combined bactericidal activity of perfluorooctyl bromide and aminoglycosides against Pseudomonas aeruginosa

J Antimicrob Chemother. 2002 Dec;50(6):939-44. doi: 10.1093/jac/dkf226.

Abstract

Perfluorooctyl bromide (PFOB) may be useful as a medium for antibiotic delivery to treat pneumonia during liquid ventilation.

Objective: The purpose of the study was to determine the antibacterial activity of PFOB either alone or in combination with aminoglycosides against Pseudomonas aeruginosa.

Design: Modified time-kill assays were used to determine antibacterial activity: an inoculum of 1 x 10(5) cfu/mL was added to PFOB, or PFOB + an aminoglycoside (1 x MIC). Viable counts were performed at 0, 0.25, 0.5, 0.75, 1, 2, 4 and 6 h. Electron microscopy was used to visualize the effect. Approximately 1.5 x 10(8) cfu/mL of bacteria were added to HEPES buffer (control), PFOB, gentamicin and PFOB + gentamicin. At baseline and 0.5 h, the bacteria were viewed under 20,000x magnification for both negative staining and thin-sectioning experiments.

Results: Exposure to PFOB alone resulted immediately in a >90% reduction in the inoculum at baseline compared with control (P = 0.001). Following the initial reduction in colony count, bacteria grew in a similar manner to controls for PFOB-exposed strains. Aminoglycosides, alone at 1 x MIC or with PFOB, produced a bacteriostatic effect over the 6 h period. PFOB-exposed P. aeruginosa showed cell wall irregularity under electron microscopy. The gentamicin-exposed P. aeruginosa showed blebbing. PFOB + gentamicin caused extensive cell wall damage, exhibiting the additive effects of PFOB and gentamicin.

Conclusion: PFOB appears to affect the cell wall of P. aeruginosa and enhance the bacterial cell destruction caused by aminoglycosides. The combined antibacterial effect of PFOB with the aminoglycosides is greater than that observed with these agents alone.

MeSH terms

  • Aminoglycosides / pharmacology*
  • Anti-Bacterial Agents*
  • Drug Therapy, Combination / pharmacology*
  • Fluorocarbons / pharmacology*
  • Hydrocarbons, Brominated
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Fluorocarbons
  • Hydrocarbons, Brominated
  • perflubron