CYP2C19*17 genetic polymorphism--an uncommon cause of voriconazole treatment failure

Diagn Microbiol Infect Dis. 2015 Sep;83(1):46-8. doi: 10.1016/j.diagmicrobio.2015.05.002. Epub 2015 May 7.

Abstract

We describe an immunosuppressed, 48-year-old male, allogeneic hematopoietic stem cell transplant recipient with severe graft-versus-host disease who developed invasive pulmonary Aspergillus fumigatus infection 6 months after transplant. His lack of response to voriconazole and undetectable serum trough levels of the drug led us to establish that he had the uncommon cytochrome P450, CYP2C19*17 allele, which leads to a rapid metabolism of voriconazole but not of the other azole antifungals. We discuss the particular challenges encountered in this case.

Keywords: Aspergillosis; CYP2C19 polymorphism; Hematopoietic stem cell transplant; Ultra metabolizer; Voriconazole.

Publication types

  • Case Reports

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy*
  • Aspergillus fumigatus / drug effects*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Humans
  • Immunocompromised Host
  • Inactivation, Metabolic
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Stem Cell Transplantation / adverse effects
  • Transplantation, Homologous / adverse effects
  • Treatment Failure
  • Voriconazole / therapeutic use*

Substances

  • Antifungal Agents
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Voriconazole