Antifungal Susceptibility Testing for Systemic Mycoses

Introduction Compared to antibacterial drugs, antimicrobial agents available for treatment of invasive fungal infections are sparse. Amphotericin B (polyene) was the first drug introduced in the 1950s, followed by flucytosine (pyrimidine) in the 1970s, and first-generations azoles (fluconazole, itraconazole) in the 1990s. Triazoles (voriconazole, posaconalzole) and echinocandins (caspofungin, micafungin, anidulafungin) became available more recently, with isavuconazole added in 2015. Although most fungi remain susceptible to many of these drugs, expanding use of antifungal therapy due to a steadily growing immunocompromized population and potentially the use of azoles in agriculture, has led to elevated resistance rates among clinical isolates [1]. Important examples of increasingly observed resistance-patterns include fluconazole resistance in Candida glabrata and triazole cross-resistance in Aspergillus fumigatus. In addition, co-resistance has been described for C. glabrata strains displaying resistance to both azoles and echinocandins [1]. Therefore, antimicrobial susceptibility testing (AST) may be important to predict the probable outcome of therapy in patients infected with unusual fungal isolates for which susceptibility patterns cannot be predicted, or in those patients that do not respond to therapy. In order to determine drug susceptibilities for yeasts and moulds, two methodologies that are based on broth microdilution (BMD) are widely accepted: one was established by the Clinical and Laboratory Standards Institute (CLSI) [2-5] and the other by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Although minor differences remain, both BMD techniques have been harmonized in recent years and overall produce comparable results. In addition to BMD, disk diffusion methods for Candida spp. and some moulds have been release by CLSI, but are more limited and less frequently used.