Épidémiologie de la résistance des champignons : impact de nos prescriptions d'antifongiques

Antifungal treatments intrinsequely harbors the risk of modifications of fungal infection epidemiology with occurrence of resistance. The YEASTS program is an active epidemiological and mycological surveillance program of yeast fungemia in the Paris area since 10 years. Until now, no major modification of the Candida species distribution and their susceptibility profile to antifungals has been observed. However, pre-exposure to antifungal drugs before the onset of fungemia deeply modifies species distribution (Candida glabrata and Candida krusei emergence with fluconazole; Candida parapsilosis, Candida glabrata and Candida krusei with caspofungin). If empirical or prophylactic antifungal treatments were generalized, one could fear a persistant increase of species with lower susceptibilities to antifungal drugs. For Aspergillus fumigatus, some countries report a 5-6% frequency of triazole-resistant isolates. The main mechanism is a mutation in cyp51A coding for the 14-alpha-demethylase enzyme, target for the azole drugs. This mutation has been observed in Europe, North America, and Asia. The principal hypothesis for its occurrence and dispersal is the massive agricultural use of azole drugs. The risk is then to inhale azole-resistant spores. If the phenomenon increased, this would threaten the use of azole for first line therapy and for prophylaxis. This would also threaten the only antifungal class orally available. Each hospital caring after patients at risk for aspergillosis should monitor the antifungal susceptibility of Aspergillus fumigatus and initiate a reflexion on the good usage of antifungal drugs.