Association of therapeutic response and levels of amphotericin B and fluconazole in different biological samples of fungal infections of the central nervous system patients

Abstract

The treatment of fungal infections of the central nervous system is impaired by the limited number of antifungal agents available and by the fact that their efficacy depends on their penetration into the cerebrospinal fluid (CSF). Patients with neuromycoses frequently present complex clinical signs and symptoms and may require individualized treatment including the monitoring of drug levels. An insufficient concentration of amphotericin B and of other antifungal agents in the tissues of these patients under treatment is a possible explanation for cases of drug treatment failure. On the other hand, yeast resistance to azole drugs has been reported and has had an impact on the empirical treatment of certain fungal infections. Neurocryptococcosis is an opportunistic infection of immunocompromised patients which has proved with some frequency to be refractory to the usual treatment with amphotericin B and fluconazole. Within this context, the objectives of the present project are to evaluate in vitro the susceptibility to amphotericin B and fluconazole of yeast cells isolated from CSF using the disk-diffusion and automated microdilution methods, and to determine the levels of these antifungal agents in biological samples (CSF, plasma and urine) by high performance liquid chromatography. The results obtained with these techniques will be compared, with emphasis on the association of these data with clinical aspects and with the response to treatment of the patients with fungal infection of the central nervous system. The expectation is that the results obtained will make relevant contributions, permitting the refinement and individualization of treatment of neuromycoses, and thus resulting in higher probability of patient survival. (AU)