The Brazilian Journal of Infectious Diseases The Brazilian Journal of Infectious Diseases
Original article
Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections
Letícia Aparecida Schiavea, Erika Nascimentoa,, , Fernando Crivelenti Vilara, Tissiana Marques de Haesb, Osvaldo Massaiti Takayanaguib, Cristiane Masetto de Gaitanic, Roberto Martineza
a Universidade de São Paulo (USP), Faculdade de Medicina de Ribeirão Preto, Departamento de Clínica Médica, Ribeirão Preto, SP, Brazil
b Universidade de São Paulo (USP), Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto, SP, Brazil
c Universidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil
Received 21 July 2017, Accepted 20 October 2017
Abstract

Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400–800mg.

Keywords
Fluconazole, Cryptococcosis, Cerebrospinal fluid