Evaluation of fusidic acid in therapy of experimental Staphylococcus aureus meningitis.
OBJECTIVE
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.
Østergaard
Christian
C
Division of Microbiology, Department of Research and Development, Statens Serum Institut, Copenhagen, Artillerivej 5, DK-2300 Copenhagen S, Denmark. coa@ssi.dk
Yieng-Kow
Runa Vavia
RV
Knudsen
Jenny Dahl
JD
Frimodt-Møller
Niels
N
Espersen
Frank
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005672:Fusidic Acid / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005947:Glucose / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D007958:Leukocyte Count; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008712:Methicillin / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000627:therapeutic use; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D010406:Penicillins; D005672:Fusidic Acid; D005947:Glucose; D008712:Methicillin