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Combined bactericidal activity of perfluorooctyl bromide and aminoglycosides against Pseudomonas aeruginosa
Rose Jung1, Susan L Pendland, Steven J Martin
1The University of Colorado Health Sciences Center, School of Pharmacy, Denver, USA.
Unlabelled:
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.
Insights
Perfluorooctyl bromide (PFOB) enhances aminoglycoside effectiveness against Pseudomonas aeruginosa by damaging cell walls. This combination shows greater antibacterial activity than either agent alone, suggesting potential for pneumonia treatment.
Area of Science:
- Microbiology
- Pharmacology
- Biomedical Engineering
Background:
- Perfluorooctyl bromide (PFOB) is explored as a potential medium for antibiotic delivery.
- Pneumonia treatment during liquid ventilation may benefit from novel drug delivery systems.
Purpose of the Study:
- To assess the antibacterial activity of PFOB alone and with aminoglycosides.
- To investigate the efficacy against Pseudomonas aeruginosa.
Main Methods:
- Modified time-kill assays were employed to measure bacterial reduction over time.
- Electron microscopy visualized the effects of PFOB and gentamicin on bacterial cell structure.
Main Results:
- PFOB alone caused an immediate >90% reduction in bacterial inoculum.
- Aminoglycosides with PFOB demonstrated enhanced bacteriostatic effects and significant cell wall damage.
- Combined treatment showed additive damage compared to individual agents.
Conclusions:
- PFOB impacts the cell wall of P. aeruginosa.
- PFOB potentiates the antibacterial action of aminoglycosides.
- The combination therapy exhibits superior antibacterial effects.
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