title: CYP2C19*17 genetic polymorphism--an uncommon cause of voriconazole treatment failure.
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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: mabidi@outlook.com.
authors.forename: Maheen Z
authors.initials: MZ
authors.lastname: Abidi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: D'Souza
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Loyola University Medical Center, Maywood, IL, USA; Division of Infectious Diseases, Department of Medicine, Edward Hines, Jr. Veterans Administration Hospital, Hines, IL, USA.
authors.forename: Krutika
authors.initials: K
authors.lastname: Kuppalli
authors.affiliation: Divison of Microbiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ledeboer
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Parmeswaran
authors.initials: P
authors.lastname: Hari
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D006801:Humans; D016867:Immunocompromised Host; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D017211:Treatment Failure; D065819:Voriconazole / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
keywords: Aspergillosis; CYP2C19 polymorphism; Hematopoietic stem cell transplant; Ultra metabolizer; Voriconazole