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Background: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast‐like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole‐resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene. Methods: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI‐M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance. Results: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast‐like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single‐nucleotide polymorphisms (I242V and D490E). Conclusions: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients. [ABSTRACT FROM AUTHOR]

Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary aspergillosis (IPA) is a leading cause of death in immunocompromised patients, particularly those receiving chemotherapy and among bone marrow transplant recipients. Aspergillus fumigatus is the most prevalent causative agent and voriconazole is the first-line therapy for IPA. In this study, we report the first isolation of voriconazole-resistant A. fumigatus carrying TR46/Y121F/T289A mutations from an immunocompromised pregnant lady in Kuwait. The patient was successfully treated for a probable respiratory infection with caspofungin and voriconazole. The literature review from PubMed has identified itraconazole-resistant clinical and environmental A. fumigatus isolates with TR34/L98H mutations in the cyp51A from several Middle Eastern countries including Kuwait. However, clinical A. fumigatus isolates with cyp51A TR46/Y121F/T289A mutations have not been reported previously from any country in the region while environmental isolates have been reported only from Iran. The source of voriconazole-resistant A. fumigatus CYP51A TR46/Y121F/T289A mutant in our patient remained unknown. Surveillance for azole resistance among clinical and environmental isolates of A. fumigatus is warranted in Kuwait. [ABSTRACT FROM AUTHOR]

Background: Azole-resistant Aspergillus fumigatus (ARAf), reported as a global public health concern, has been unexpectedly observed in different countries., Aim: To identify ARAf and detect azole resistance related to the CYP51A mutation in different hospital environmental samples., Methods: In this multi-centre study from Iran, surfaces of electronic equipment and appliances from different hospitals in Iran were sampled using cotton swabs. All samples were cultured using azole-containing agar plates (ACAPs). Recovered Aspergillus isolates were identified at the species level using partial DNA sequencing of the β-tubulin gene. The azole susceptibility testing of A. fumigatus isolates was performed using the Clinical and Laboratory Standards Institute M38-A3 guideline. The sequencing of the CYP51A gene was also performed to detect mutations related to resistance., Findings: Out of the 693 collected samples, 89 (12.8%) Aspergillus species were recovered from ACAPs. Aspergillus fumigatus (41.6%) was the most prevalent, followed by A. tubingensis (23.6%) and A. niger (15.6%). Among 37 isolates of A. fumigatus, 19 (51.3%) showed high minimum inhibitory concentration (MIC) values to at least one of the three azoles, voriconazole, itraconazole, and posaconazole. CYP51A polymorphisms were detected in all 19 isolates, of which 52.6% showed the TR 34 /L98H mutation. Other detected mutations were G432C, G448S, G54E/G138C, F46Y, and Y121F/M220I/D255E. T289F and G432C were the first reported mutations in ARAf., Conclusion: There was a considerable level of azole resistance in hospital environmental samples, a serious warning for patients vulnerable to aspergillosis. Our findings have also revealed a different mutation pattern in the CYP51A gene., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Azole resistance in Aspergillus is emerging in European and Asian countries. As azoles are mainstay of therapy in the management of aspergillosis, azole resistance has serious implications in patient management. We report the emergence of resistance to triazoles in environmental Aspergillus fumigatus isolates in Iran. The TR34/L98H mutation was the only resistance mechanism. Overall 3.3% of the A. fumigatus isolates from hospital surroundings in Sari and Tehran had the same TR34/L98H STR Af genotype and were related to some resistant clinical and environmental TR34/L98H isolates from the Netherlands and India. It is emphasised that routine resistance surveillance studies focusing on environmental and clinical samples are warranted to yield the true prevalence of azole resistance in A. fumigatus in Iran. [ABSTRACT FROM AUTHOR]

Tricyclazole as a common fungicide wildly used to control rice blast disease in the Asian country may induce azole resistance in Aspergillus fumigatus isolates. The main reason of the acquired azole resistance is probably environmental exposure through wide fungicide use in agriculture. The present study was conducted with the aim of investigating the current status of the azole-resistant A. fumigatus obtained from the paddy fields with exposure to tricyclazole. A total of 108 soil samples were collected from four different locations of paddy fields in Mazandaran Province, Iran. Pure fungal colonies were initially identified based on the conventional tools, and then reconfirmed by using DNA sequencing of the partial ß-tubulin gene. In addition, the in vitro antifungal susceptibility was determined using the Clinical and Laboratory Standards Institute document (CLSI) M38-A2. The identification of the mutations in the CYP51A gene was accomplished by the implementation of the polymerase chain reaction amplification assay on the selected isolates. Overall, 31 of 108 (28.7%) isolates were identified as A. fumigatus, four (3.7%) of which were recognized as azole-resistant with MICs of itraconazole ≥8μg/ml and voriconazole ≥4μg/ml. Only two out of the four azole-resistant A. fumigatus isolates harboured TR34/L98H variant and the other two isolates were identified as azole-resistant without any CYP51A gene mutations. However, other point mutations (TR46/Y121F/T289A) were not detected in the CYP51A gene. The high molecular structure similarity between environmental and medical triazoles may result in the selection of resistance mechanisms. Nonetheless, one might conclude that tricyclazole with different molecular structures against medical azoles induces azole-resistance in A. fumigatus isolates. The behavior of such pesticides as tricyclazole in the rice paddy fields would have an effective role in the development of azole-resistance that requires detailed information., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)