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JAC Advance Access originally published online on April 14, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 1301-1305
© 2003 The British Society for Antimicrobial Chemotherapy

Evaluation of fusidic acid in therapy of experimental Staphylococcus aureus meningitis

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

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

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

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

* Corresponding author. Tel: +45-32683575; Fax: +45-32683887; E-mail: coa{at}ssi.dk


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