The emergence of azole resistance in Aspergillus fumigatus complex in New Zealand.

Background: Azole resistance in Aspergillus fumigatus (A. fumigatus) is increasing globally. A pan-azole-resistant isolate prompted genetic analysis of local azole-resistant isolates to determine resistance genotypes.

Methods: All A. fumigatus complex isolates were tested by the broth colorimetric micro-dilution method, Sensititre® YeastOne® (SYO) (TREK Diagnostic Systems, West Sussex, England). Epidemiological cutoff values derived from the Clinical & Laboratory Standards Institute method were used to determine the proportion of non-wild-type (non-WT) isolates (ie, those with an increased likelihood to harbour acquired mechanisms of resistance). Non-WT isolates were identified by ß-tubulin gene sequencing and the genotype for azole resistance was determined. The history of the patient with the first pan-resistant isolate was reviewed along with the treatment history of patients with azole-resistant strains.

Results: From January 2001 to August 2020, antifungal susceptibility testing was performed on 260 A. fumigatus complex isolates: six isolates were non-WT for one or more azole agent, two A. fumigatus sensu stricto and four other members within the species complex: two A. fischeri and two A. lentulus. There were three non-WT isolates for amphotericin B, three for itraconazole, five for posaconazole and five for voriconazole. All six non-WT strains were isolated in the past nine years (P<0.01), and four in the past three years. Azole-resistance genotyping for the A. fumigatus sensu stricto isolates detected amino acid changes at hot spots in the cyp51A gene: one at G54E and one at G138C. All six isolates were WT for caspofungin. Five of the six patients with azole-resistant strains had previous azole treatment, and the patient with the pan-azole-resistant strain had been on continuous azole treatment for 42 months preceding strain isolation.

Conclusions: New Zealand can be added to the growing list of countries with azole-resistant A. fumigatus complex isolates, including pan-azole resistance in A. fumigatus sensu stricto. While uncommon and mostly found in cryptic species within the complex, azole resistance is increasing. The results provide a baseline for monitoring this emerging antifungal resistance trend in A. fumigatus in New Zealand.