Skip Navigation



JAC Advance Access published online on April 14, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg231
© 2003 by The British Society for Antimicrobial Chemotherapy
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
51/5/1301    most recent
dkg231v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Østergaard, C.
Right arrow Articles by Espersen, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Østergaard, C.
Right arrow Articles by Espersen, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2003 The British Society for Antimicrobial Chemotherapy

Brief report

Evaluation of fusidic acid in therapy of experimental Staphylococcus aureus meningitis

Christian Østergaard 1*, Runa Vavia Yieng-Kow 1, Jenny Dahl Knudsen 1, Niels Frimodt-Møller 1, Frank Espersen 1

1 Division of Microbiology, Department of Research and Development, Statens Serum Institut, Copenhagen, Artillerivej 5, DK-2300 Copenhagen S, Denmark

* Corresponding author. E-mail: coa{at}ssi.dk.

Received 20 January 2003 ; revised 6 February 2003 ; accepted 27 February 2003

Abstract

Objectives: Combination therapy that includes fusidic acid, an antimicrobial agent highly active against staphylococci, has been recommended in the treatment of patients with Staphylococcus aureus meningitis. The aim of this study was to evaluate the pharmacokinetic, CSF bactericidal and anti-inflammatory properties of fusidic acid.

Methods: The pharmacokinetics, treatment efficacy and parameters of the meningeal inflammatory response were studied in rabbits, using an experimental meningitis model against S. aureus (MICs of fusidic acid and methicillin were 0.125 and 1 mg/L, respectively).

Results: Fusidic acid entered the CSF, with peak values within 0.5-1 h of the intravenous bolus injection/infusion and with a percentage penetration (AUCCSF/AUCserum) into uninfected and purulent CSF of 1.9% ± 0.7 and 4.5% ± 0.7, respectively. Rabbits treated with antibiotics [fusidic acid 80 mg/kg/6 h (n = 6), methicillin 80 mg/kg/3 h (n = 7) and the two combined (n = 6)] had significantly higher bacterial kill rates than untreated controls (n = 6, P < 0.05). Combination therapy was less effective, with significantly less killing after 6 h of treatment than methicillin alone (P < 0.05). CSF white blood cells and CSF levels of interleukin-8 (IL-8), glucose, lactate and protein were altered during staphylococcal meningitis, but with no significant difference between antibiotic-treated and untreated rabbits.

Conclusions: Antagonism between methicillin and fusidic acid was observed in staphylococcal meningitis.

Keywords: fusidic acid, Staphylococcus aureus, meningitis, methicillin, antagonism
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.