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JAC Advance Access originally published online on June 26, 2009
Journal of Antimicrobial Chemotherapy 2009 64(3):563-566; doi:10.1093/jac/dkp224
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Synergistic effects of aminoglycosides and fosfomycin on Pseudomonas aeruginosa in vitro and biofilm infections in a rat model

Yun Cai{dagger}, Yan Fan{dagger}, Rui Wang*, Mao-Mao An and Bei-Bei Liang

Department of Clinical Pharmacology, PLA General Hospital, Beijing 100853, People's Republic of China

Received 7 March 2009; returned 28 April 2009; revised 2 June 2009; accepted 3 June 2009

* Corresponding author. Tel: +86-10-6693-7908; Fax: +86-10-8821-4425; E-mail: caicaihh{at}sohu.com

Objectives: To study the in vitro and in vivo efficacy of aminoglycosides against Pseudomonas aeruginosa, either alone or in combination with fosfomycin.

Methods: Using an in vitro study to assess inhibition of the growth of P. aeruginosa, MIC90 and MIC50 values of amikacin, gentamicin, netilmicin, tobramycin and isepamicin were determined, either alone or in combination with fosfomycin, and then the fractional inhibitory concentration index was calculated. In the biofilm-infected rat model, the efficacy and effects of treatment with isepamicin and fosfomycin on infection were studied.

Results: The combinations of amikacin and fosfomycin or isepamicin and fosfomycin showed the most significant synergistic effects against P. aeruginosa as compared with other treatments. In the biofilm-infected rat model, as a single agent, neither isepamicin nor fosfomycin reduced C-reactive protein level and numbers of white blood cells, or reduced the colony counts of the bacteria from both tissue and silica gel tubes. However, the combination of these two agents resulted in a good therapeutic effect.

Conclusions: Combination of aminoglycosides and fosfomycin not only showed a positive effect in vitro but also improved the therapeutic effect in a biofilm-infected rat model. This offers an effective treatment strategy against some therapy-resistant infections.

Keywords: isepamicin , amikacin , gentamicin , netilmicin , tobramycin

{dagger} These authors contributed equally to the work.


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