Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany

Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar.Phenotypic MICs were obtained from selected, molecularly confirmed isolates.cyp51A gene sequencing and genotyping of azole-resistant isolates were done.Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR 46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.Conclusion: This is the first report of A fumigatus with TR 46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region. K E Y W O R D SAspergillus fumigatus, azole resistance, compost, TR 34 /L98H, TR46/Y121F/T289A | 431 AHANGARKANI et Al.

Section: Discussionmentioning

confidence: 73%

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

Ahangarkani

Puts

Nabili

et al. 2020

“…Until now, few studies have evaluated azole‐resistant A. fumigatus in CF patients, whose prevalence varied greatly between centres and countries, and in all cases were <10% 14,15,22‐24 …”

Section: Discussionmentioning

confidence: 99%

“…Only limited data are available regarding the prevalence of azole‐resistant A. fumigatus isolates in CF subjects. The two largest studies investigating azole‐resistant A. fumigatus in CF patients were from the Netherlands 14 and Germany 15 . The Dutch multicentre study reported that 7.1% of A. fumigatus isolates were azole‐resistant with TR34/L98H (80%) being the dominating resistance mechanism followed by TR46/T289A/Y121F (16.4%), M220 (1.8%) and G54W (1.8%) 14 .…”

Section: Introductionmentioning

confidence: 99%

“…The Dutch multicentre study reported that 7.1% of A. fumigatus isolates were azole‐resistant with TR34/L98H (80%) being the dominating resistance mechanism followed by TR46/T289A/Y121F (16.4%), M220 (1.8%) and G54W (1.8%) 14 . The German multicentre study reported that the overall prevalence of azole resistance per patient was 5.3% with the TR34/L98H mutation being the most prevalent (88%) 15 . Since data from Argentina, and particularly from patients with CF are limited, this study aimed to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus in a cohort of Argentinean patients with CF.…”

Section: Introductionmentioning

confidence: 99%

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High prevalence of triazole‐resistant Aspergillus fumigatus sensu stricto in an Argentinean cohort of patients with cystic fibrosis

Devoto

Hermida‐Alva

Posse

et al. 2020

Summary Background Triazole resistance in Aspergillus fumigatus sensu stricto due to mutations in the cyp51A gene has been widely reported. Data from Argentina, and particularly from cystic fibrosis (CF) patients, are limited. Objectives To investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus sensu stricto recovered from this population. Methods Ninety‐three A. fumigatus isolates from 50 CF patients were retrospectively analysed for azole resistance using the standard microbroth dilution method according to CLSI M38‐A2 guidelines. Sequencing analysis of the cyp51A gene and its promoter region was conducted in those isolates displaying high MIC values to itraconazole, voriconazole and/or posaconazole. Results Overall, 14% of isolates displayed high MIC values to at least one azole. Of them, 30.7% had the mutation TR34‐L98H. No mutations in the cyp51A gene or its promoter were found in the remaining non–wild‐type strains. Therefore, other mechanisms associated with azole resistance can be highly prevalent in these isolates. Conclusions To the best of our knowledge, this is the first study in Latin America reporting azole‐resistant A. fumigatus strains recovered from respiratory secretions of CF patients. Noteworthy, the prevalence of azole resistance in A. fumigatus sensu stricto in the studied Argentinean CF population is alarmingly high.

“…All C. bertholletiae isolates were further tested using broth microdilution according to the EUCAST 9.3 standard as described elsewhere . Susceptibility was assessed for amphotericin B, itraconazole, voriconazole, caspofungin (Sigma‐Aldrich Life Sciences, Taufkirchen, Germany), posaconazole, micafungin, anidulafungin (mcePharma, Bilovec, Tschechien) and isavuconazole (Basilea Pharmaceutica, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Comparison of genotyping methods for Cunninghamella bertholletiae

Verhasselt

Radke

Schmidt

et al. 2019

Summary Background Invasive fungal infections caused by filamentous fungi of the order Mucorales are serious complications in immunocompromised patients and often associated with fatal outcome. As a member of this order, Cunninghamella bertholletiae is a saprophytic fungus with naturally exhibited high minimum inhibitory concentrations against common antifungal drugs and with the potential for outbreaks in clinical settings. Objectives and methods In a proof‐of‐principle study, we evaluated the performance of microsatellite markers for the discrimination of thirteen C. bertholletiae isolates from various sources in comparison with a repetitive sequence‐based PCR (rep‐PCR) and random amplification of polymorphic DNA (RAPD). Based on the higher discriminatory power of the microsatellite PCR with five separate primer pairs (Simpson's index of 1 vs 0 [RAPD] and 0 [rep‐PCR]), the novel method was applied to eight additional isolates, including four well‐characterised isolates from a cluster of infections in a next step. Results In total, microsatellite PCR identified 21 separate genotypes. A probable epidemiological association of the cluster isolates could be demonstrated by microsatellite genotyping. Conclusion In conclusion, our findings demonstrate the value of microsatellite PCR in genotyping Cunninghamella bertholletiae and its potential for future applications with other species of the order Mucorales.