In vitro interactions of tobramycin with various nonantibiotics against Pseudomonas aeruginosa and Burkholderia cenocepacia

Treerat, P; Widmer, F; Middleton, PG; Iredell, J; George, AM

In vitro interactions of tobramycin with various nonantibiotics against Pseudomonas aeruginosa and Burkholderia cenocepacia

Treerat, P Widmer, F Middleton, PG Iredell, J George, AM

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Publication Type:: Journal Article
Citation:: FEMS Microbiology Letters, 2008, 285 (1), pp. 40 - 50
Issue Date:: 2008-08-01

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Field	Value	Language
dc.contributor.author	Treerat, P	en_US
dc.contributor.author	Widmer, F	en_US
dc.contributor.author	Middleton, PG	en_US
dc.contributor.author	Iredell, J	en_US
dc.contributor.author	George, AM https://orcid.org/0000-0003-4691-8960	en_US
dc.date.issued	2008-08-01	en_US
dc.identifier.citation	FEMS Microbiology Letters, 2008, 285 (1), pp. 40 - 50	en_US
dc.identifier.issn	0378-1097	en_US
dc.identifier.uri	http://hdl.handle.net/10453/9640
dc.description.abstract	Pseudomonas aeruginosa and Burkholderia cepacia are the major pathogens that colonize the airway surface and cause progressive respiratory failure and high mortality, especially in cystic fibrosis (CF) patients. Tobramycin is the treatment of choice, but persistent usage enables the infectious organisms to activate defence mechanisms, making eradication rarely successful. Combinations of antibiotic and nonantibiotic compounds have been tested in vitro against P. aeruginosa and B. cepacia, but with mixed results. Sodium ions interfere with the bacterial tobramycin uptake system, but amiloride partially reverses this antagonism. In this pilot study, we extend previous findings of the effectiveness of tobramycin in combination with amiloride and other nonantibiotics against a P. aeruginosa type strain, and against four P. aeruginosa strains and one Burkholderia cenocepacia strain isolated from CF patients. Significantly, the four clinical P. aeruginosa strains were tobramycin resistant. We also find that Na+ and K+, but not Cl -, are the chief antagonists of tobramycin efficacy. These results suggest that chemotherapy for CF patients might not only be compromised by antibiotic-resistant pathogens alone, but by a lack of penetration of antibiotics caused either by bacterial biofilms or the high sodium flux in the CF lung, or by antagonistic effects of some drug combinations, any of which could allow the persistence of drug-susceptible bacteria. © 2008 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.	en_US
dc.relation.ispartof	FEMS Microbiology Letters	en_US
dc.relation.isbasedon	10.1111/j.1574-6968.2008.01219.x	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Burkholderia cepacia complex	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Burkholderia Infections	en_US
dc.subject.mesh	Pseudomonas Infections	en_US
dc.subject.mesh	Cystic Fibrosis	en_US
dc.subject.mesh	Amiloride	en_US
dc.subject.mesh	Tobramycin	en_US
dc.subject.mesh	Drug Therapy, Combination	en_US
dc.subject.mesh	Microbial Sensitivity Tests	en_US
dc.subject.mesh	Drug Resistance, Bacterial	en_US
dc.subject.mesh	Drug Interactions	en_US
dc.subject.mesh	Membrane Transport Modulators	en_US
dc.title	In vitro interactions of tobramycin with various nonantibiotics against Pseudomonas aeruginosa and Burkholderia cenocepacia	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	285	en_US
utslib.for	1108 Medical Microbiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	07 Agricultural and Veterinary Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
dc.location.activity	ISI:000257658900006	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	285	en_US

Abstract:

Pseudomonas aeruginosa and Burkholderia cepacia are the major pathogens that colonize the airway surface and cause progressive respiratory failure and high mortality, especially in cystic fibrosis (CF) patients. Tobramycin is the treatment of choice, but persistent usage enables the infectious organisms to activate defence mechanisms, making eradication rarely successful. Combinations of antibiotic and nonantibiotic compounds have been tested in vitro against P. aeruginosa and B. cepacia, but with mixed results. Sodium ions interfere with the bacterial tobramycin uptake system, but amiloride partially reverses this antagonism. In this pilot study, we extend previous findings of the effectiveness of tobramycin in combination with amiloride and other nonantibiotics against a P. aeruginosa type strain, and against four P. aeruginosa strains and one Burkholderia cenocepacia strain isolated from CF patients. Significantly, the four clinical P. aeruginosa strains were tobramycin resistant. We also find that Na+ and K+, but not Cl -, are the chief antagonists of tobramycin efficacy. These results suggest that chemotherapy for CF patients might not only be compromised by antibiotic-resistant pathogens alone, but by a lack of penetration of antibiotics caused either by bacterial biofilms or the high sodium flux in the CF lung, or by antagonistic effects of some drug combinations, any of which could allow the persistence of drug-susceptible bacteria. © 2008 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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http://hdl.handle.net/10453/9640