Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases

Yanan Zhao, Christen R. Stensvold, David S. Perlin, Maiken C. Arendrup

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Objectives: 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 tandemrepeat/L98Hmutation 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.

Original languageEnglish (US)
Pages (from-to)1497-1504
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number7
DOIs
StatePublished - Jul 2013

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology

Keywords

  • A. fumigatus
  • Azole resistant
  • CYP51A PCR
  • GM

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