Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The
triazole antifungal agents itraconazole,
voriconazole,
isavuconazole and
posaconazole are treatment options against diseases caused by Aspergillus However, resistance to
azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo
azole resistance occurs occasionally in patients during
azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of
azole-based fungicides. Although ubiquitously distributed, A. fumigatus is not a phytopathogen. However, agricultural fungicides deployed against plant pathogenic moulds such as Fusarium, Mycospaerella and A. flavus also show activity against A. fumigatus in the environment and exposure of non-target fungi is inevitable. Further, similarity in molecule structure between
azole fungicides and antifungal drugs results in cross-resistance of A. fumigatus to medical
azoles. Clinical studies have shown that two-thirds of patients with
azole-resistant
infections had no previous history of
azole therapy and high mortality rates between 50% and 100% are reported in
azole-resistant invasive
aspergillosis. The resistance phenotype is associated with key mutations in the cyp51A gene, including TR34/L98H, TR53 and TR46/Y121F/T289A resistance mechanisms. Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis,
azole monotherapy should be avoided.
Liposomal amphotericin B or a combination of
voriconazole and an
echinocandin are recomended for
azole-resistant
aspergillosis.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.