Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection

Voriconazole is the recommended agent for invasive aspergillosis, with lipid amphotericin B or caspofungin as second line treatment choices. Being the only agents available in oral formulation, azoles are used in chronic infections and often over longer time periods. In addition to being used in clinical medicine, azoles are employed extensively in agriculture. Azole-resistant Aspergillus has been isolated in azole naive patients, in azole exposed patients and in the environment. The primary underlying mechanism of resistance is as a result of alterations in the cyp51A target gene, with a variety of mutations found in clinical isolates but just one identified in a environmental strain (a point mutation at codon 98 accompanied by a tandem repeat in the promoter region). Much less is currently known about echinocandin resistance in Aspergillus, in part because susceptibility testing is not routinely performed and because the methods suffer from technical difficulties and suboptimal reproducibility. Clinical breakthrough cases have been reported however, and resistance has been confirmed in vivo. In this paper we review the current knowledge on epidemiology, susceptibility testing and underlying mechanisms involved in azole and echinocandin resistance in Aspergillus