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

ABSTRACT

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.