Azole Resistance in Moulds—Approach to Detection in a Clinical Laboratory

The multitude of factors has contributed to the increasing number of fungal infections caused by species of difficult-to-treat opportunistic moulds, such as Fusarium, Scedosporium, and cryptic Aspergilli. Also, rare fungi sporadically encountered, such as Rasamsonia argillacea, Penicillium oxalicum, and melanized fungi, are now well recognized. The high mortality associated with these rare and uncommon fungi is primarily linked to the difficulty in diagnosis and limited therapeutic options, as many of them exhibit resistance to antifungals including azoles. Azole resistance in Aspergillus fumigatus has been increasingly reported because standardized methods for susceptibility testing and associated clinical breakpoints and epidemiological cutoff values became available. However, such advances in antifungal susceptibility testing (AFST) in non-Aspergillus moulds barring mucorales have been lacking. Notwithstanding the fact that the true incidence of these non-Aspergillus filamentous moulds in clinical settings is hitherto unknown, also data on AFST by standardized methods is largely lacking. Determination of minimum inhibitory concentration (MIC) by reference techniques is the gold standard to detect azole resistance in filamentous fungi. In recent years, some progress has been made toward the description of resistance mechanisms at molecular level especially in Aspergillus. This paper reviews the present state of azole resistance in Aspergillus and other filamentous mould species and discusses their relevance to clinical practice.