Isavuconazole for treatment of refractory coccidioidal meningitis with concomitant cerebrospinal fluid and plasma therapeutic drug monitoring

Med Mycol. 2021 Sep 3;59(9):939-942. doi: 10.1093/mmy/myab035.

Abstract

Coccidioidal meningitis (CM) is a life-threatening infection with limited treatment options. Small series have reported success with isavuconazole; however, limited data exist on cerebrospinal fluid (CSF) penetration. Paired plasma and CSF isavuconazole concentrations were measured. Eleven CSF levels were tested, (7 ventricular, 4 lumbar) in three CM patients. Ventricular CSF levels were undetectable despite detectable plasma levels. All lumbar CSF levels were detectable (mean 1.00 µg/ml). Three pairs of lumbar CSF/plasma concentrations taken within 1 h of each other yielded a mean CSF/plasma ratio of 0.31. Isavuconazole was detectable in lumbar but not ventricular CSF in three patients treated for refractory CM.

Lay summary: Isavuconazole is a triazole antifungal that has been used as salvage therapy in the treatment of coccidioidal meningitis (CM). Few data exist characterizing its concentration in the cerebrospinal fluid (CSF). We report tandem plasma and CSF concentrations of isavuconazole in three patients with CM.

Keywords: azole antifungal; central nervous system; endemic fungi; isavuconazonium; pharmacokinetics.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / therapeutic use*
  • Cerebrospinal Fluid / drug effects*
  • Coccidioidomycosis / drug therapy*
  • Drug Monitoring
  • Female
  • Humans
  • Male
  • Meningitis, Fungal / drug therapy*
  • Nitriles / blood
  • Nitriles / cerebrospinal fluid
  • Nitriles / pharmacokinetics
  • Nitriles / therapeutic use
  • Plasma / drug effects*
  • Pyridines / blood
  • Pyridines / cerebrospinal fluid
  • Pyridines / therapeutic use*
  • Treatment Outcome
  • Triazoles / blood
  • Triazoles / cerebrospinal fluid
  • Triazoles / therapeutic use*
  • Young Adult

Substances

  • Antifungal Agents
  • Nitriles
  • Pyridines
  • Triazoles