title: Rate of cyp51A mutation in Aspergillus fumigatus among lung transplant recipients with targeted prophylaxis.
abstract: OBJECTIVE
  The most common mechanism of azole (itraconazole and voriconazole) resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of our study was to determine the rate of cyp51A mutations in lung transplant recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole.
  
  
  METHODS
  We conducted a prospective study that included 22 LTR with A. fumigatus between October 2008 and November 2011. Of those, 10 LTR were colonized with A. fumigatus and 12 had invasive pulmonary aspergillosis.
  
  
  RESULTS
  Four patients were found to have A. fumigatus isolates with a cyp51A mutation, two had colonization and two had invasive pulmonary aspergillosis. The remaining 18 LTR had WT cyp51A A. fumigatus isolates. All A. fumigatus isolates (except one due to mixed growth) were tested for antifungal susceptibility. A total of nine LTR were exposed to azoles prior to A. fumigatus isolation for a median duration of 249 (IQR 99-524) days. Azole exposure preceded the isolation of two mutant isolates and seven WT isolates. None of the cyp51A mutant isolates conferred phenotypic resistance to azoles.
  
  
  CONCLUSIONS
  Targeted antifungal prophylaxis in LTR did not lead to cyp51A resistance mutations in this cohort. Data on larger cohorts who receive universal antifungal prophylaxis are needed.
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Shalhoub
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: M-L
authors.initials: ML
authors.lastname: Luong
authors.affiliation: Division of Microbiology, University of Manchester, Manchester, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Howard
authors.affiliation: Division of Microbiology, Hospital for Sick Children and Public Health Ontario Laboratories, Public Health Ontario, University of Toronto, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Richardson
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: L G
authors.initials: LG
authors.lastname: Singer
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Chaparro
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Akinlolu
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Rotstein
authors.affiliation: Division of Microbiology, Hospital for Sick Children and Public Health Ontario Laboratories, Public Health Ontario, University of Toronto, Toronto, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Mazzulli
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Toronto, Canada shahid.husain@uhn.ca.
authors.forename: S
authors.initials: S
authors.lastname: Husain
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D018890:Chemoprevention / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D016040:Lung Transplantation; D059645:Mutation Rate; D011446:Prospective Studies; D055732:Pulmonary Aspergillosis / Q000382:microbiology*; D066027:Transplant Recipients; D065819:Voriconazole / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole
keywords: antifungal; resistance; transplantation