title: Triazole Resistance inAspergillus fumigatusClinical Isolates Obtained in Nanjing, China.
abstract: BACKGROUND
  During the past decades, the incidence of invasive aspergillosis (IA) caused by Aspergillus fumigatus has increased dramatically. The aims of this study were to investigate the susceptibility of clinical isolates of A. fumigatus to triazole and the underlying cyp51A mutations in triazole-resistant A. fumigatus.
  
  
  METHODS
  A total of 126 A. fumigatus clinical isolates from 126 patients with proven or probable IA were obtained from four large tertiary hospitals in Nanjing, China, between August 2012 and July 2015. The determination of minimal inhibitory concentrations (MICs) for itraconazole, voriconazole, and posaconazole was performed by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing reference method.
  
  
  RESULTS
  A total of 4 A. fumigatus isolates (3.17%) were confirmed to be itraconazole resistant, with MICs of ≥8 mg/L, and one isolate (0.8%) was confirmed to be voriconazole resistant and posaconazole resistant, with MICs of 4 mg/L and 0.5 mg/L, respectively. We found that two of the 4 isolates of triazole-resistant A. fumigatus had the L98H amino acid substitution in combination with a 34-base pair tandem repeat in the promoter region, one isolate had an M220I mutation, and another itraconazole-resistant isolate did not have a substitution in the cyp51A gene.
  
  
  CONCLUSIONS
  This study shows that triazole-resistant A. fumigatus clinical isolates are present in Nanjing, China, which is a new challenge to the clinical management of IA.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China.
authors.forename: Chun-Lai
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics; D002681:China; D025141:Drug Resistance, Fungal; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D020080:Tandem Repeat Sequences / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D065819:Voriconazole