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

Braz J Infect Dis. 2018 Jan-Feb;22(1):11-15. doi: 10.1016/j.bjid.2017.10.003. Epub 2017 Nov 13.

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: Cerebrospinal fluid; Cryptococcosis; Fluconazole.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • Adult
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood*
  • Antifungal Agents / cerebrospinal fluid*
  • Candidiasis / blood
  • Candidiasis / cerebrospinal fluid
  • Candidiasis / drug therapy
  • Chromatography, High Pressure Liquid
  • Cryptococcosis / blood
  • Cryptococcosis / cerebrospinal fluid
  • Cryptococcosis / drug therapy*
  • Cryptococcus / drug effects
  • Cryptococcus / isolation & purification
  • Dose-Response Relationship, Drug
  • Fluconazole / administration & dosage
  • Fluconazole / blood*
  • Fluconazole / cerebrospinal fluid*
  • Histoplasmosis / blood
  • Histoplasmosis / cerebrospinal fluid
  • Histoplasmosis / drug therapy
  • Humans
  • Microbial Sensitivity Tests
  • Middle Aged
  • Reference Values
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Fluconazole