Azole resistance in Aspergillus isolates by different types of patients and correlation with environment ‐ An Italian prospective multicentre study (ARiA study)

Abstract

Background A wide range of frequency of azole‐resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options. Objectives Estimate the prevalence of azole‐resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment. Methods Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole‐resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole‐resistant isolates from previous Italian studies. Results 425 Aspergillus isolates from 367 patients were analysed. The azole‐resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole‐resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR34/L98H. No correlation between the clinical resistant strains and environmental isolates from patients’ home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole‐resistant genotypes starting from a founder azole‐resistant genotype. Conclusions This study confirms the trend of azole‐resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

Azole resistance in Aspergillus fumigatus. The first 2‐year's Data from the Danish National Surveillance Study, 2018–2020

“…In comparison to other surveillance studies, our azole resistance prevalence was higher than the 3.2% found in 2009 to 2011 in a multicentre study with 19 countries, 31 but lower than the 11% in the more recent Dutch nationwide surveillance in 2017 and 2018 22 . Larger studies and surveillances on azole resistance in A. fumigatus are summarised in Table 3 22,25,32–39 . These studies show that the azole resistance prevalence in the present surveillance is in line with other European studies from 2011 to 2018 and the Netherlands from 2007 to 2009.…”

“…22 Larger studies and surveillances on azole resistance in A. fumigatus are summarised in Table 3. 22,25,[32][33][34][35][36][37][38][39] These studies show that the This study is associated with both strengths and limitations. The primary strength is that it is nationwide and thus population based.…”

Five‐year surveillance study of clinical and environmental Triazole‐ResistantAspergillus fumigatus isolates in Iran

“…14,15 In addition, the dispersal activity of ARAf spores leads to geographical transfer is an argument in support of the emergence of these cross-resistant isolates in different countries. 14,[16][17][18][19][20] One major mechanism of azole resistance in A. fumigatus is mutations in the target enzyme sterol demethylase (cyp51A) gene. The enzyme 14-sterol demethylase is the main target for triazoles encoded by the cyp51A gene.…”

“…There is a potential link between residues of azole fungicides with similar chemical structures to triazole medicines in soil and the emergence of triazole‐resistance 14,15 . In addition, the dispersal activity of ARA f spores leads to geographical transfer is an argument in support of the emergence of these cross‐resistant isolates in different countries 14,16–20 . One major mechanism of azole resistance in A. fumigatus is mutations in the target enzyme sterol demethylase ( cyp51A ) gene.…”

In Vitro Activity of Novel Lipopeptides against Triazole-Resistant Aspergillus fumigatus

“…Italian data showed that azole-resistant clinical/environmental Aspergillus spp. represented 7% of the isolates [ 6 ]. The resistance mechanisms included alteration in the cyp51A gene and promoter and upregulation of its expression [ 5 ].…”