RESUMEN
Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.
Asunto(s)
Antibacterianos/líquido cefalorraquídeo , Ácido Fusídico/líquido cefalorraquídeo , Inflamación/tratamiento farmacológico , Meningitis Bacterianas/tratamiento farmacológico , Rifampin/líquido cefalorraquídeo , Staphylococcus epidermidis/efectos de los fármacos , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Líquido Cefalorraquídeo/química , Ácido Fusídico/sangre , Ácido Fusídico/uso terapéutico , Humanos , Inflamación/microbiología , Masculino , Meningitis Bacterianas/microbiología , Persona de Mediana Edad , Rifampin/sangre , Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiologíaRESUMEN
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.