Aspergillus fumigatus and pan-azole resistance: who should be concerned?

Although clinical outcomes in the treatment of aspergillosis have markedly improved with the availability of newer triazoles, the development of resistance to these antifungals, especially in Aspergillus fumigatus, is a growing concern. The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis.

Resistance may develop through either patient or environmental azole exposure. Environmental exposure is the most prevalent means of resistance development, and these isolates can cause disease in various at-risk groups, which now include those with influenza, and potentially COVID-19. Although current treatment options are limited, newer therapies are in clinical development. These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus.

Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. Certain geographic regions and patient populations appear to be at increased risk for this pathogen. As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. While treatment options are currently limited, new agents under clinical development may offer hope.