JAC Advance Access originally published online on November 1, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 939-944
© 2002 The British Society for Antimicrobial Chemotherapy
Combined bactericidal activity of perfluorooctyl bromide and aminoglycosides against Pseudomonas aeruginosa
1 The University of Colorado Health Sciences Center, School of Pharmacy, Denver, CO; 2 The University of Illinois at Chicago, College of Pharmacy, Chicago, IL; 3 The University of Toledo, College of Pharmacy, 2801 West Bancroft Street, Toledo, OH 43606, USA
Received 20 June 2002; returned 2 August 2002; revised 22 August 2002; accepted 28 August 2002
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 timekill assays were used to determine antibacterial activity: an inoculum of 1 x 105 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 108 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.
Keywords: perfluorooctyl bromide, aminoglycoside, Pseudomonas aeruginosa, bactericidal activity, electron microscopy
* Corresponding author. Tel: +1-419-530-1964; Fax: +1-419-530-1950; E-mail: smartin2{at}utnet.utoledo.edu