High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates in a specialist cardiothoracic centre

Abdolrasouli, Alireza; Scourfield, Andrew; Rhodes, Johanna; Elborn, J. Stuart; Fisher, Matthew C.; Schelenz, Silke; Armstrong‐James, Darius

doi:10.1016/j.ijantimicag.2018.08.004

Cited by 43 publications

(42 citation statements)

References 26 publications

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“…In Australia where the incidence of azole resistance is low (< 3%), 2/3 azole resistant isolates had the G54R mutation associated with high MICs to itraconazole and posaconazole (Talbot et al, 2018). A recent study from the United Kingdom employing the AsperGenius assay R (PathoNostics BV) showed that 16/22 (73%) isolates with the resistant phenotype harbored no mutations detected by this test (Abdolrasouli et al, 2018). The FungiplexR Aspergillus Azole-R IVD real-time PCR platform is also now available.…”

Section: Molecular Methods To Detect Azole Resistance In Aspergillus mentioning

confidence: 99%

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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Section: Molecular Methods To Detect Azole Resistance In Aspergillus mentioning

confidence: 99%

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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“…Studies have shown that AR Af isolates harbouring resistance-associated cyp51A variants are globally distributed, and are often found alongside wild-type A. fumigatus in a diverse set of environmental substrates, including: agricultural soil (13, 14), flower beds (13, 15–17) and timber mills (18). Moreover, clinical cases of aspergillosis with AR Af isolates harbouring either TR 34 /L98H or TR 46 /Y121F/T289A continue to emerge (19, 20), with one study specifically linking a fatal case of aspergillosis to a genotypically indistinguishable isolate sourced from the patients own home (21). Retrospective studies of patients with invasive aspergillosis (IA) and infected with azole-resistant genotypes of A. fumigatus show an excess mortality of 25% at day 90 when compared against patients with wild-type-infections (22).…”

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confidence: 99%

Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom

Sewell¹,

Zhang²,

Brackin³

et al. 2019

Preprint

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8Azole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily 9 by two environmentally-associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. Using an 10 environmental sampling strategy across the South of England we assess the prevalence of azole resistant 11 A. fumigatus (ARAf) in soil samples collected in both urban and rural locations. We characterise the 12 susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic 13 basis of resistance and investigate their genetic relationships. ARAf was detected in 6.7% of the soil 14 samples, with a higher prevalence in urban (13.8%) compared to rural (1.1%) locations. Nineteen 15 isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical 16 azoles, with 18 isolates exhibiting resistance to itraconazole, four to voriconazole, with two also showing 17 additional elevated minimum inhibitory concentration to posaconazole. Thirteen of the resistant isolates 18 harboured the TR34/L98H resistance allele and six isolates carried TR46/Y121F/T289A allele. The 19 azole-19 resistant isolates were spread across five csp1 genetic subtypes, t01, t02, t04B, t09 and t18 with t02 the 20 predominant subtype. Our study demonstrates that ARAf can be easily isolated in the South of England, 21 especially in urban city centres, which appear to play an important role in the epidemiology of 22 environmentally-linked drug resistant A. fumigatus. 23 24

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“…Studies have shown that ARAf isolates harboring resistance-associated cyp51A variants are globally distributed and are often found alongside wild-type (WT) A. fumigatus in a diverse set of environmental substrates, including agricultural soil (14,15), flower beds (14,(16)(17)(18), and timber mills (19). Moreover, clinical cases of aspergillosis with ARAf isolates harboring either TR 34 /L98H or TR 46 /Y121F/T289A continue to emerge (20,21), with one study specifically linking a fatal case of aspergillosis to a genotypically indistinguishable isolate sourced from the patient's own home (22). Retrospective studies of patients with invasive aspergillosis (IA) and infected with azole-resistant genotypes of A. fumigatus show an excess mortality of 25% at day 90 when compared with that of patients with wild-type infections, suggesting a growing clinical impact caused by the emergence of ARAf (23).…”

mentioning

confidence: 99%

Elevated Prevalence of Azole-Resistant Aspergillus fumigatus in Urban versus Rural Environments in the United Kingdom

Sewell

Zhang

Brackin

et al. 2019

Antimicrob Agents Chemother

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Azole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily by the following two environmentally associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. By sampling soils across the South of England, we assess the prevalence of azole-resistant A. fumigatus (ARAf) in samples collected in both urban and rural locations. We characterize the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance, and investigate their genetic relationships. ARAf was detected in 6.7% of the soil samples, with a higher prevalence in urban (13.8%) than rural (1.1%) locations. Twenty isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical azoles, with 18 isolates exhibiting resistance to itraconazole, 6 to voriconazole, and 2 showing elevated minimum inhibitory concentrations to posaconazole. Thirteen of the resistant isolates harbored the TR34/L98H resistance allele, and six isolates carried the TR46/Y121F/T289A allele. The 20 azole-resistant isolates were spread across five csp1 genetic subtypes, t01, t02, t04B, t09, and t18 with t02 being the predominant subtype. Our study demonstrates that ARAf can be easily isolated in the South of England, especially in urban city centers, which appear to play an important role in the epidemiology of environmentally linked drug-resistant A. fumigatus.

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High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates in a specialist cardiothoracic centre

Cited by 43 publications

References 26 publications

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom

Elevated Prevalence of Azole-Resistant Aspergillus fumigatus in Urban versus Rural Environments in the United Kingdom

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