Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

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 400-800 mg.

Histoplasmosis del sistema nervioso central en un paciente inmunocompetente / Histoplasmosis of the central nervous system in an immunocompetent patient

La histoplasmosis es una afección polifacética producida por el hongo dimorfo Histoplasma capsulatum , cuyas esporas son inhaladas y llegan al pulmón, órgano primario de infección. La forma meníngea, considerada como una de las manifestaciones más graves de esta micosis, suele presentarse en individuos con alteraciones en la inmunidad celular: pacientes con síndrome de inmunodeficiencia humana adquirida, con lupus eritematoso sistémico o con trasplante de órgano sólido, así como en lactantes, debido a su inmadurez inmunológica. La forma de presentación más usual es de resolución espontánea y se observa en individuos inmunocompetentes que se han expuesto a altas concentraciones de conidias y fragmentos miceliares del hongo. En estas personas, la afección se manifiesta por trastornos pulmonares y por la posterior diseminación a otros órganos y sistemas. Se presenta un caso de histoplasmosis del sistema nervioso central en un niño inmunocompetente.

Histoplasmosis is a multifaceted condition caused by the dimorphic fungi Histoplasma capsulatum whose infective spores are inhaled and reach the lungs, the primary organ of infection. The meningeal form, considered one of the most serious manifestations of this mycosis, is usually seen in individuals with impaired cellular immunity such as patients with acquired immunodeficiency syndrome, systemic lupus erythematous or solid organ transplantation, and infants given their immunological immaturity. The most common presentation is self-limited and occurs in immunocompetent individuals who have been exposed to high concentrations of conidia and mycelia fragments of the fungi. In those people, the condition is manifested by pulmonary disorders and late dissemination to other organs and systems. We report a case of central nervous system histoplasmosis in an immunocompetent child.

Histoplasmose do sistema nervoso central: estudo do líquido cefalorraqueano em 8 pacientes / Histoplasmosis of the central nervous system: study of cerebrospinal fluid in 8 patients

Foram estudads 113 amostras de LCR de 8 pacientes no período compreendido entre setembro-1980 e agosto-1992. Todos os pacientes apresentavam quadro clínico e do LCR compatível a processo meningoencefálico de evoluçäo protraída. Nenhum deles apresentava a síndrome de imunodeficiência adquirida. Em todos foi feito o diagnóstico de histoplasmose do SNC: em todos foram detectados anticorpos a Histoplasma capsulatum no LCR; em um foi isolada a levedura por cultura em meio de Sabouraud. As principais características do LCR por ocasiäo do diagnóstico foram: pleocitose moderada com presomínio de células linfomononucleadas porém com presença de neutrófilos e por vezes eosinófilos; hiperproteinorraquia moderada, hipoglicorraquia; aumento moderado do teor de globulinas gama. Os pacientes foram acompanhados durante períodos que variaram de 7 a 102 meses e submetidos a exames periódicos de LCR, em funçäo da sintomatologia clínica. O número de células do LCR e a concentraçäo de proteinas totais apresentaram evoluçäocaracterizada pela ocorrência de episódios de exacerbaçäo com perfil parcialmente dissociado, favorecendo as proteínas. As concentraçöes de glicose eram moderadamente baixas sendo os menores valores coincidentes aos períodos de exarcebaçäo do número de células. Os teores de globulinas gama apresentaram também oscilaçöes, porém menos evidentes. Submetidos os pacientes a tratamento eficaz, ocorreu no LCR: rápida diminuiçäo do número de células; aumento da taxa de glicose; lento decréscimo dos aumentos de proteínas e de globulinas gama