Background: Chronic pulmonary aspergillosis (CPA) patients often require long-term antifungal therapy. Resistance to at least one of the triazole antifungal drugs has been found in 28% of clinical isolates of Aspergillus fumigatus causing exacerbations, yet their origin is uncertain. The high discriminatory power of genotyping methods (based on tandem repeats) may be helpful for discerning the source of A. fumigatus infections and may reflect antifungal resistance patterns.
Methods: The performance of two genotyping methods: nSTRAf  and TRESP was compared to determine the relationship among isolates from the same patient, and whether genotypes with different resistance patterns could be distinguished. We identified distinct genotypes in 31 clinical isolates from 14 CPA patients located in different geographical regions in the UK and compared them to two reference isolates (ATCC46645,  AF293).
Results: A wide distribution of A. fumigatus isolates was found across the UK: 23 genotypes according to nSTRAf and 18 according to TRESP. The Simpson index of discriminatory power for nSTRAf  and TRESP was 0.9699 and 0.9398, respectively. The relationship between genotype and susceptibility patterns was variable: in some patients, resistance developed in one genotype over time, while in others, the same susceptibility patterns was reflected in different genotypes, suggesting the causal organisms were different. Isolates were not discriminated geographically.
Future work: I. Analysis of a greater number of isolates is required to decipher whether nSTRAf and TRESP typing reflects triazole resistance in the UK.  II. Although technically challenging, nSTRAf may be more representative of relatedness, although addition of TRESP ERG4b data may allow better discrimination of these isolates.   III. An expanded set of NAC CPA patient isolates, including those with verified TR34/L98H mutations, analysed by next generation sequencing will allow further discrimination of these relationships.

Comparison of two genotyping methods reveals clusters of resistant Aspergillus fumigatus from chronic pulmonary aspergillosis patients in the UK