Ecdc Issues Risk Assessment On Azole Resistance In Aspergillus From Environmental Azole Fungicide.

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Today the European Centre for Disease Prevention and Control (ECDC) issued a risk assessment report on azole resistance in Aspergillus spp. and its possible link to environmental usage of azole fungicides. An increase of strains of Aspergillus causing serious human infection showing resistance to azole antifungals has been detected in several European countries although the number of studies is small. However, a high rate of therapy failures has been reported in patients having Aspergillusisolates resistant to triazole antifungals. The majority of resistant isolates are multi-azole-resistant and therefore, triazole drugs would be marginalised in the management of azole resistant aspergillosis. Although the environmental link of the resistance has not been fully proven, there are several findings that point at a relationship:

1. The presence of azole-resistant Aspergillus isolates in patients that had not previously received azole antifungals;

2. The presence of a tandem repeat in the promoter of the target gene cyp51A, which is a genomic change not found in any of the A. fumigatus isolates that have become resistant through patient therapy, but has been found in azole-resistant phytopathogenic moulds;

3. The recovery of A. fumigatus isolates from the environment in Europe which genetically cluster to patient A. fumigatus with the tandem repeat and are distinct from wild type, susceptible A. fumigatusisolates;

4. The fact that medical azole-resistant A. fumigatus isolates are also cross-resistant to five triazole fungicides used as pesticides;

5. The molecule alignment and docking of these five triazole fungicides into the active site of the Cyp51A enzyme is identical to that of the medical azoles.

Two meetings with experts from Europe and the USA were organized by ECDC in order to analyse the potential implications for human health of the resistance of Aspergillus to antifungal drugs as well as the possible link of the resistance with the environmental use of azole fungicides in agriculture. This report is the product of those meetings.View report

The report estimates that in the European region 2,100,00 and 240,000 patients suffer from allergic and chronic aspergillosis, respectively. The annual incidence of invasive aspergillosis has been estimated at 63,250 cases. In summary, the overall burden of aspergillosis in Europe has been estimated at around 2,400,000 individuals annually. Currently triazole antifungals are the first line therapy of invasive aspergillosis but they are also widely used to treat chronic pulmonary aspergillosis and allergic aspergillosis. Therefore the emerging issue of resistance is significant both for human health and for the agricultural community.

In summary, resistance of Aspergillus to azole antifungals is a matter of concern. The reports concludes about the need to improve surveillance to get good and reliable data about resistance in A. fumigatus. It all recommends accelerating progress on direct molecular detection of resistance from clinical specimens, even if culture negative. It also identifies the need for further research into the causes for the development of triazole resistance, in particular to investigate the environmental origin of azole resistance, and how reversible this with alternative fungicide treatments.