First Detection of TR 46 /Y121F/T289A and TR 34 /L98H Alterations in Aspergillus fumigatus Isolates from Azole-Naive Patients in Denmark despite Negative Findings in the Environment
| Autor: | G. M. Thomsen, T. M. Hassan, Rasmus Hare Jensen, E. G. Mathiasen, Mette Krogh Christensen, K. M. T. Astvad, U. G. Pedersen, Maiken Cavling Arendrup, O. Hilberg |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Azoles Male Antifungal Agents Genotype Denmark Population Microbial Sensitivity Tests Environment Aspergillosis Microbiology Rhizomucor pusillus Aspergillus fumigatus Fungal Proteins Mechanisms of Resistance Drug Resistance Fungal medicine Humans Pharmacology (medical) education Genotyping Aged Pharmacology Aspergillus Fungal protein education.field_of_study biology Middle Aged biology.organism_classification medicine.disease Infectious Diseases Female Microsatellite Repeats |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 58:5096-5101 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.02855-14 |
| Popis: | Azole-resistant Aspergillus fumigatus harboring the TR 34 /L98H or TR 46 /Y121F/T289A alterations is increasingly found in Europe and Asia. Here, we present the first clinical cases of TR 46 /Y121/T289A and three cases of TR 34 /L98H outside the cystic fibrosis (CF) population in Denmark and the results of environmental surveys. Four patients (2012 to 2014) with 11 A. fumigatus and 4 Rhizomucor pusillus isolates and 239 soil samples (spring 2010 and autumn 2013, respectively) with a total of 113 A. fumigatus isolates were examined. Aspergillus isolates were screened for azole resistance using azole-containing agar. Confirmatory susceptibility testing was done using the EUCAST microbroth dilution EDEF 9.1 reference method. For relevant A. fumigatus isolates, CYP51A sequencing and microsatellite genotyping were performed. Three patients harbored TR 34 /L98H isolates. Two were azole naive at the time of acquisition and two were coinfected with wild-type A. fumigatus or R. pusillus isolates, complicating and delaying diagnosis. The TR 46 /Y121F/T289A strain was isolated in 2014 from a lung transplant patient. Genotyping indicated that susceptible and resistant Aspergillus isolates were unrelated and that no transmission between patients occurred. Azole resistance was not detected in any of the 113 soil isolates. TR 34 /L98H and TR 46 /Y121F/T289A alterations appear to be emerging in the clinical setting in Denmark and now involve azole-naive patients. Two recent soil-sampling surveys in Denmark were unable to indicate any increased prevalence of azole-resistant A. fumigatus in the environment. These findings further support the demand for real-time susceptibility testing of all clinically relevant isolates and for studies investigating the seasonal variation and ecological niches for azole-resistant environmental A. fumigatus . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|