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Published on: September 8, 2021
Evaluation of fusidic acid in therapy of experimental Staphylococcus aureus meningitis
Christian Østergaard1, Runa Vavia Yieng-Kow, Jenny Dahl Knudsen
1Division of Microbiology, Department of Research and Development, Statens Serum Institut, Copenhagen, Artillerivej 5, DK-2300 Copenhagen S, Denmark. coa@ssi.dk
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.
Insights
Combination therapy for Staphylococcus aureus meningitis using fusidic acid and methicillin showed antagonism, with methicillin alone being more effective. Further research is needed to optimize treatment strategies for this serious infection.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Staphylococcus aureus meningitis is a serious infection.
- Combination therapy with fusidic acid is recommended.
- The efficacy and properties of fusidic acid in meningitis require further evaluation.
Purpose of the Study:
- To evaluate the pharmacokinetic, CSF bactericidal, and anti-inflammatory properties of fusidic acid.
- To assess the efficacy of fusidic acid, methicillin, and their combination in an experimental S. aureus meningitis model.
Main Methods:
- An experimental meningitis model was established in rabbits using S. aureus.
- Pharmacokinetics of fusidic acid in serum and cerebrospinal fluid (CSF) were analyzed.
- Treatment efficacy was assessed by bacterial kill rates and CSF inflammatory markers.
Main Results:
- Fusidic acid demonstrated penetration into the CSF.
- Both fusidic acid and methicillin monotherapies increased bacterial kill rates compared to controls.
- Combination therapy showed antagonism, with methicillin monotherapy being more effective than the combination.
Conclusions:
- An antagonistic interaction was observed between methicillin and fusidic acid in the treatment of S. aureus meningitis.
- Methicillin monotherapy was more effective than combination therapy in this model.
- Current combination therapy recommendations may need reevaluation.
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