Since the mid-1990ies, a steady increase in the occurrence of itraconazole resistant Aspergillus fumigatus isolates has been observed in clinical contexts leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele, termed ‘TR34/L98H’ which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of azole resistant A. fumigatus and underlying cyp51A-mutations in clinical and environmental samples in Germany. From a total of 522 clincial samples, 2.9% showed elevated MIC values for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. Among resistant isolates, the TR34/L98H cyp51A allele was most prevalent, but also isolates with other substitutions were found. For six isolates no mutations in cyp51A were found indicating the presence of other mechanisms. Out of 455 environmental samples 12% were positive for azole resistant A. fumigatus. The most prevalent resistance alleles were TR34/L98H and TR46/Y121F/T289A, dispersed along a West-East corridor across Northern Germany. Genotyping showed that strains with either allele formed distinct and potentially clonal groups, while other resistances correlated with genotypes also highly prevalent in susceptible strains. In conclusion, the prevalence of azole resistant A. fumigatus is lower in our clinical test set than previously reported for other countries. Although the TR34/L98H mutation frequently occurs among azole resistant strains in Germany, it is not the only resistance mechanism present. The similar geographical distribution of the major resistance alleles and genotypes in the German environment and in clinical samples suggests that occurrence of resistant A. fumigatus strains in patients is a direct consequence of environmental exposure.
1. O Bader, M Weig, U Reichard, R Lugert, M Kuhns, M Christner, J Held, S Peter, U Schumacher, D Buchheidt, K Tintelnot, U Groß, and MykoLabNet-D Partner (2013). cyp51A-based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. Antimicrob Agents Chemother 57(8):3513-7.
Full conference title:
- ISHAM 19th (2015)