Fungi in the order Mucorales cause acute, invasive and frequently fatal infections in susceptible patients. This study aimed to perform a systematic review of all reported mucormycosis cases during the last 25 years in Iran. After a comprehensive literature search, we identified 98 cases in Iran from 1990-2015. The mean patient age was 39.8 ± 19.2 years. Diabetes was the most common underlying condition (47.9%), and 22.4% of the patients underwent solid organ or bone marrow transplantation. The most common clinical forms of mucormycosis were rhinocerebral (48.9%), pulmonary (9.2%) and cutaneous (9.2%). Eight cases of disseminated disease were identified. Overall mortality in the identified cases was 40.8%, with the highest mortality rate in patients diagnosed with disseminated infection (75%). The mortality rate in rhinocerebral infection patients was significantly lower (45.8%). Rhinocerebral infection was the most common clinical manifestation in diabetes patients (72.9%). Patients were diagnosed using various methods including histopathology (85.7%), microscopy (12.3%) and culture (2.0%). Rhizopus species were the most prevalent (51.7%), followed by Mucor species (17.2%). Sixty-nine patients were treated with a combination of surgery and antifungal therapy (resulting survival rate, 66.7%). Owing to the high mortality rate of advanced mucormycosis, early diagnosis and treatment may significantly improve survival rates. Therefore, increased monitoring and awareness of this life-threatening disease is critical.

Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l À1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR 34 /L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

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.

Onychomycosis is a common nail disorder resulting from the invasion of the nail plate by a dermatophyte, yeast or mould species and gives rise to some diverse clinical presentations. The purpose of the present study was to isolate and identify the causative fungi of onychomycosis in the population of Tehran, Iran. Nail samples from 504 patients with prediagnosis of onychomycosis during 2005 were examined both by direct microscopical observation of fungal elements in KOH preparations and in culture for the identification of the causative agent. All samples were inoculated on (i) Sabouraud dextrose agar (SDA, Merck), (ii) SDA with 5% chloramphenicol and cycloheximide in duplicate for dermatophyte and (iii) SDA with 5% chloramphenicol in triplicate for mould isolation. The criteria for the diagnosis of onychomycosis caused by non-dermatophytic moulds were based on microscopical observation of fungal elements, growth of the same mould in all triplicate culture and no growth of a dermatophyte or yeast in all the cultures. Of 504 cases examined, 216 (42.8%) were mycologically proven cases of onychomycosis (144 fingernails, 72 toenails). Among the positive results, dermatophytes were diagnosed in 46 (21.3%), yeasts in 129 (59.7%) and non-dermatophytic moulds in 41 (19%). Trichophyton mentagrophytes was the most common causative agent (n = 22), followed by Trichophyton rubrum (n = 13), Candida albicans (n = 42), Candida spp. (n = 56) and Aspergillus spp. (n = 21). Nearly half of the clinically suspected fungal nail infections are onychomycosis and yeast is responsible for most of the infections in Iran.

Background: Recent studies from multiple countries have shown a high prevalence of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) among severely ill patients. Despite providing valuable insight into the clinical management of CAPA, large-scale prospective studies are limited. Here, we report on one of the largest multicenter epidemiological studies to explore the clinical features and prevalence of COVID-19-associated pulmonary mold infections (CAPMIs) among mechanically ventilated patients.Methods: Bronchoalveolar lavage (BAL) and serum samples were collected for culture, galactomannan (GM), and β-D-glucan (BDG) testing. Patients were classified as probable CAPMI based on the presence of host factors, radiological findings, and mycological criteria.Results: During the study period, 302 COVID-19 patients were admitted to intensive care units (ICUs), among whom 105 were mechanically ventilated for ≥4 days. Probable CAPMI was observed among 38% of patients (40/105), among whom BAL culture of 29 patients turned positive for molds, while galactomannan testing on BAL (GM index ≥1) and serum (GM index >0.5) samples were positive for 60% (24/40) and 37.5% (15/39) of patients, respectively. Aspergillus (22/29; 75.8%) and Fusarium (6/29; 20.6%) constituted 96.5% of the molds isolated. Diaporthe foeniculina was isolated from a COVID-19 patient. None of the patients who presented with CAPMI were treated with antifungal drugs.Conclusion: Despite being prevalent, the absence of appropriate antifungal treatment highlights that CAPMI is a neglected complication among mechanically ventilated COVID-19 patients admitted to ICUs. CAPMI can be caused by species other than Aspergillus.