title: Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases.
abstract: OBJECTIVE
  Triazole resistance in Aspergillus fumigatus has been increasing. We explored the A. fumigatus azole resistance profiles in bronchoalveolar lavage (BAL) fluid samples from Danish patients examined for aspergillosis.
  
  
  METHODS
  A total of 94 BAL samples from 87 patients were evaluated by galactomannan (GM) test and A. fumigatus CYP51A profiling by PCR.
  
  
  RESULTS
  Aspergillus spp. were isolated from 27/48 (56.3%) cultured samples, including 23 A. fumigatus with one resistant strain (4.3%). Samples were classified into GM-positive (≥3.0), GM-intermediate (0.5 to <3.0) and GM-negative (<0.5) groups, where the CYP51A PCR was positive in 81.8% (36/44), 56.3% (18/32) and 38.9% (7/18) of samples, respectively. Nine CYP51A PCR-positive samples (9/61, 14.8%) were found to have mutations resulting in amino acid substitutions. M220V was detected from a sample culture positive for susceptible A. fumigatus and P216L was found in a culture-negative BAL sample. Conversely, no mutation was found in one sample culture positive for azole-resistant A. fumigatus. The tandem repeat/L98H mutation was not detected.
  
  
  CONCLUSIONS
  Our study shows that azole resistance in A. fumigatus can be cryptic and may go undiagnosed. The combination of improved culture/susceptibility tests and the direct molecular detection of resistance markers will facilitate prompt institution of appropriate antifungal therapy.
authors: Public Health Research Institute Center, UMDNJ-NJMS, Newark, NJ 07103, USA.
authors: Yanan
authors: Y
authors: Zhao
authors: Christen R
authors: CR
authors: Stensvold
authors: David S
authors: DS
authors: Perlin
authors: Maiken C
authors: MC
authors: Arendrup
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D001393:Azoles / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003718:Denmark; D025141:Drug Resistance, Fungal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D055732:Pulmonary Aspergillosis / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus
keywords: A. fumigatus; CYP51A PCR; GM; azole resistant