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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 TR46 /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 TR46 /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.

Summary 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 TR46/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 TR46/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.

Cystic fibrosis (CF) is associated with increased rates of morbidity and mortality due to fungal and bacterial colonisation of the airways or respiratory infections. The prevalence of fungi in Iranian CF population has been underestimated. Therefore, the current study was conducted to define the frequency of fungi in respiratory specimens obtained from Iranian CF patients based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed on the obtained isolates according to the guidelines from the Clinical and Laboratory Standards Institute. A cohort of 42 CF patients, including 29 males and 13 females, were categorised according to the referenced diagnostic criteria. Candida albicans (n = 24, 80%), C. dubliniensis (n = 2, 6.6%), C. parapsilosis (n = 2, 6.6%), C. tropicalis (n = 1, 3.3%), C. glabrata (n = 1, 3.3%) and Meyerozyma caribbica (n = 1, 3.3%) were isolated from 73.8% of the CF patients. Aspergillus terreus (n = 3, 42.8%) was identified as the most common Aspergillus species, followed by A. fumigatus (n = 2, 28.5%), A. oryzae (n = 1, 14.2%) and A. flavus (n = 1, 14.2%). Bacterial and fungal co-colonisation was detected in 7 (16.6%) and 22 (52.3%) samples that were positive for Aspergillus and Candida species, respectively. However, Scedosporium species and Exophiala dermatitidis never were detected. In terms of geometric mean (GM) minimum inhibitory concentrations (MICs), posaconazole (0.018 μg/mL) and caspofungin (0.083 μg/mL) exhibited the highest antifungal activities against all Candida species. In addition, posaconazole exhibited the lowest MIC range (0.008-0.063 μg/mL) against all Aspergillus species, followed by caspofungin (0.016-0.125 μg/mL) and voriconazole (0.125-0.25 μg/mL). To conclude, it is essential to adopt a consistent method for the implementation of primary diagnosis and determination of treatment regimen for the CF patients. However, further studies are still needed to better define the epidemiology of fungal organisms in CF patients from the Middle East and the clinical significance of their isolation.

In recent decades the incidence of Candida endocarditis has increased dramatically. Despite the application of surgery and antifungal therapy, Candida endocarditis remains a life-threatening infection with significant morbidity and mortality. We report a 37-year-old male drug abuser presenting with high fever, chest pain, loss of appetite and cardiac failure. His echocardiography revealed mobile large tricuspid valve vegetations. Fungal endocarditis was confirmed by culturing of the resected vegetation showing mixed growth of Candida albicans and Candida tropicalis, although three consecutive blood cultures were negative for Candida species. Phenotypic identification was reconfirmed by sequencing of the internal transcribed spacer (ITS rDNA) region. The patient was initially treated with intravenous fluconazole (6 mg kg−1 per day), followed by 2 weeks of intravenous amphotericin B deoxycholate (1 mg kg−1 per day). Although MICs were low for both drugs, the patient’s antifungal therapy combined with valve replacement failed, and he died due to respiratory failure.