Azole antifungal resistance today: focus on Aspergillus

Abstract

Oral triazole therapy is well established for the treatment of invasive aspergillosis (IPA), allergic aspergillosis (ABPA), and chronic pulmonary aspergillosis (CPA), and is often long-term. Resistance to triazole azole antifungal drugs in Aspergillus fumigatus is now a major clinical problem in a number of European locations, in China, Canada and the USA with particularly high frequencies from the north-west of the UK, and The Netherlands. A number of centers are reporting the continuing increasing frequency and evolution of resistance mechanisms in A. fumigatus, in both azole-naïve and patients treated with azoles. The increasing rate of resistance is of concern. A number of resistance mechanisms have been found. The biofilm modality of Aspergillus growth may have a number of therapeutic implications for aspergillosis, including antifungal resistance. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance. Direct resistance testing in culture-negative clinical samples may add additional insights into the prevalence of azole resistance in A. fumigatus.