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In recent years, the widespread emergence of drug resistance in yeasts and filamentous fungi to existing antifungal armamentariums has become a severe threat to global health. There is also concern regarding increased rates of azole resistance in Aspergillus fumigatus and Terbinafine resistance in Trichophyton species. To overcome this concern of resistance to regular therapies, new antifungal drugs with novel and effective mechanisms are crucially needed. Herbal remedies may be promising strategies for the treatment of resistant infections. We aimed to investigate the in vitro and silico activity of piperlongumine against clinical azole susceptible/resistant A. fumigatus and terbinafine-susceptible/resistant Trichophyton species. In the current study, piperlongumine demonstrated potent antifungal activity, with minimum inhibitory concentrations (MICs) ranging from 0.016-4 μg/mL against Trichophyton isolates and 0.25-2 μg/mL for A. fumigatus isolates. Additionally, molecular docking studies indicated that piperlongumine has a strong binding affinity to the active sites of squalene epoxidase and sterol 14-alpha demethylase. However, further studies are warranted to correlate these findings with clinical outcomes and provide the basis for further investigations to pave the way for developing novel antifungal agents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Iman Haghani reports financial support was provided by Mazandaran University of Medical Sciences. This research was financially supported by grant number 17588 from Mazandaran University of Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Luliconazole (LCZ) is a topical imidazole antifungal agent with broad-spectrum activity. However, LCZ encounters challenges such as low aqueous solubility, skin retention, and penetration, which reduce its dermal bioavailability and hinder its efficacy in drug delivery. The aim of the present study was to formulate, characterize, and evaluate the in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains. The LCZ-NLCs were synthesized using a modified emulsification-solvent evaporation technique. Characterization involved assessing parameters such as poly-dispersity index (PDI), zeta potential, encapsulation efficiency (EE %), Field Emission Scanning Electron Microscopy (FESEM), Differential Scanning Calorimetry (DSC) analysis, and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR). Furthermore, in vitro drug release experiments, analysis of release kinetics, cytotoxicity assessments, and in vitro antifungal susceptibility tests were performed as part of the study. The findings indicated that LCZ-NLCs displayed nanoscale dimensions, uniform dispersion, and a favorable zeta potential. The encapsulation efficiency of LCZ in NLCs was approximately 90%. FESEM analysis revealed spherical nanoparticles with consistent shape. ATR-FTIR analysis indicated no chemical interaction between LCZ and excipients. In vitro drug release experiments demonstrated that LCZ-NLCs notably improved the drug's dissolution rate. The stability testing confirmed consistent colloidal nanometer ranges in the LCZ-NLCs samples. Additionally, cytotoxicity tests revealed no toxicity within the tested concentration. Moreover, in vitro antifungal susceptibility tests demonstrated potent antifungal activity of LCZ-NLCs against the tested resistant fungal isolates. The study findings suggest that the LCZ-NLCs formulation developed in this research could be a promising topical treatment for superficial fungal infections, especially in cases of resistant infections. However, the study needs further ex vivo and in vivo tests to ensure safety and efficacy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Burn patients are at high risk of developing secondary invasive fungal infections due to their compromised skin barrier, extensive use of antibiotics, and immunosuppression., Objectives: We investigated demographic characteristics and clinical factors associated with Candida infections in intensive care unit (ICU) burn patients, and the in vitro antifungal susceptibility of species of isolates., Methods: A total of 353 burn patients admitted to three major ICUs of burn centers in Iran were evaluated between 2021 and 2023. Patients were considered as colonisation and candidemia. Demographic characteristics, burn-related factors, and clinical conditions were compared among the groups. Furthermore, we identified fungi at the species level and performed antifungal susceptibility testing according to CLSI guidelines., Results: Overall, 46.2% of patients were colonised with a Candida species, leading to candidemia in 15.3%. The most frequently isolated species from candidemia and burn wound colonisation were Candida parapsilosis (37.0%) and Candida albicans (31.9%), respectively. Risk factors linked to candidemia included larger total body surface area (TBSA) (>50%), older patients, indwelling catheters, diabetes, and an extended ICU stay. Mortality rate was higher among candidemia patients (82.5%) compared to colonised patients (7.3%). The resistance rate of the strains isolated from candidemia to fluconazole and voriconazole was 28% and 18.2%, respectively., Conclusion: We found that a higher percentage of TBSA burn injuries, longer hospital stays, and catheterization are important predictors of candidemia. The mortality rate was significantly higher in people infected with non-albicans Candida species. Prevention and treatment strategies for candidemia should be based on updated, regional epidemiological data., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Candidiasis is a common fungal infection caused by Candida species, with Candida albicans being the most prevalent. Resistance to azole drugs, commonly used to treat Candida infections, poses a significant challenge. Transcriptional activator candidate 1 ( TAC1 ) gene has emerged as a key player in regulating drug resistance in C. albicans . This review explores the structure and function of the TAC1 gene and its role in azole resistance. This gene encodes a transcription factor that controls the expression of genes involved in drug resistance, such as efflux pump genes ( CDR1, CDR2, and MDR1 ) and ERG11 . Mutations in TAC1 can increase these genes' expression and confer resistance to azoles. Various TAC1 gene mutations, mostly gain-of-function mutations, have been identified, which upregulate CDR1 and CDR2 expression, resulting in azole resistance. Understanding the mechanisms of azole resistance mediated by the TAC1 gene is crucial for the strategies in the effective antifungal development pipeline.

Treatment-resistant dermatophytosis caused by the members of the Trichophyton mentagrophytes/Trichophyton interdigitale species group (TMTISG) is increasing worldwide. We aimed to determine the prevalence of TMTISG in patients with dermatophytosis in two centers from north of Iran and detect the possible mutations in the squalene epoxidase (SQLE) gene in relevant terbinafine (TRB) resistant pathogenic isolates. From November 2021 to December 2022, 1960 patients suspected to dermatophytosis and referred to two mycology referral laboratories in the north of Iran were included in the study. Identification of all dermatophyte isolates was confirmed by RFLP of rDNA internal transcribed spacer (ITS) regions. Antifungal susceptibility testing against five common antifungals using the CLSI-M38-A3 protocol was performed. The TMTISG isolates resistant to TRB, were further analyzed to determine the possible mutations in the SQLE gene. Totally, 647 cases (33%) were positive for dermatophytosis of which 280 cases (43.3%) were identified as members of TMTISG. These were more frequently isolated from tinea corporis 131 (44.56%) and tinea cruris 116 (39.46%). Of 280 TMTISG isolates, 40 (14.3%) were resistant to TRB (MIC ≥ 4 µg/mL), all found to be T. indotineae in ITS sequencing. In SQLE sequencing 34 (85%) of TRB-resistant isolates had coincident mutations of Phe 397 Leu and Ala 448 Thr whereas four and two isolates had single mutations of Phe 397 Leu and Leu 393 Ser, respectively. Overall, the resistance of Iranian TMTISG isolates to TRB greatly occurred by a mutation of Phe 397 Leu in the SQLE gene as alone or in combination with Ala 448 Thr. Nevertheless, for the occurrence of in vitro resistance, only the presence of Phe 397 Leu mutation seems to be decisive., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The current study aimed to identify Iranian Nakaseomyces (Candida) glabrata complex species in the clinical isolates and determine their antifungal susceptibility profile., Methods: In total, 320 N. glabrata clinical isolates were collected from patients hospitalized in different geographical regions of Iran. The initial screening was performed by morphological characteristics on CHROMagar Candida. Each isolate was identified by targeting the D1/D2 rDNA using a multiplex-PCR method. To validate the mPCR method and determine genetic diversity, the ITS-rDNA region was randomly sequenced in 40 isolates. Additionally, antifungal susceptibility was evaluated against nine antifungal agents following the CLSI M27-A4 guidelines., Results: All clinical isolates from Iran were identified as N. glabrata. The analysis of ITS-rDNA sequence data revealed the presence of eight distinct ITS clades and 10 haplotypes among the 40 isolates of N. glabrata. The predominant clades identified were Clades VII, V, and IV, which respectively accounted for 22.5%, 17.5%, and 17.5% isolates. The widest MIC ranges were observed for voriconazole (0.016-8 μg/mL) and isavuconazole (0.016-2 μg/mL), whereas the narrowest ranges were seen with itraconazole and amphotericin B (0.25-2 μg/mL)., Conclusion: Haplotype diversity can be a valuable approach for studying the genetic diversity, transmission patterns, and epidemiology of the N. glabrata complex., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aims: Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis., Methods and Results: First, an antimicrobial assay via microdilution sensitivity test was performed. Then, twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The β-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of β-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1)., Conclusion: Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Miltefosine, an alkylphosphocholine, has been approved recently for the treatment of visceral leishmaniasis. Miltefosine has shown promise as a treatment for paracoccidioidomycosis, and has mixed activity against other fungi and yeast. There are limited data on the in-vitro activity of miltefosine against azole-resistant and -susceptible Aspergillus spp. As such, the aim of this study was to determine the in-vitro activity of miltefosine against Aspergillus strains. Miltefosine was tested against 108 azole-susceptible and -resistant Aspergillus strains isolated from Iran and other countries using the broth microdilution method. Miltefosine was found to be effective against azole-resistant Aspergillus isolates, with minimum inhibitory concentrations (MICs) ranging from 1.562 to 6.25 µg/mL. MIC 50 and MIC 90 were 1.562 and 3.125 µg/mL, respectively. Miltefosine had a higher geometric mean MIC (2.459 µg/mL) for wild-type Aspergillus isolates than itraconazole (0.220 µg/mL) and voriconazole (0.298 µg/mL). No significant difference was found between miltefosine MICs for azole-resistant Aspergillus isolates and azole-susceptible Aspergillus isolates (P>0.05). Miltefosine appears to have good in-vitro activity against azole-resistant Aspergillus strains, according to these findings. Furthermore, the findings suggest that miltefosine could be used to treat infections caused by azole-resistant Aspergillus spp., Competing Interests: Competing interests None declared., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Invasive aspergillosis is one of the most common fungal infections and azole resistance in Aspergillus fumigatus (ARAf) is a growing medical concern in high-risk patients. To our knowledge, there is no comprehensive epidemiological surveillance study on the prevalence and incidence of ARAf isolates available in Iran., Objectives: The study aimed to report a five-year survey of triazole phenotypes and genotype patterns concerning the resistance in clinical and environmental A. fumigatus in Iran., Methods: During the study time frame (2016-2021), a total of 1208 clinical and environmental Aspergillus species were collected. Isolates were examined and characterised by in vitro antifungal susceptibility testing (CLSI M38 broth microdilution) and cyp51A sequencing., Results: In total, 485 Aspergillus section Fumigati strains were recovered (clinical, n = 23; 4.74% and environment, n = 462; 95.26%). Of which A. fumigatus isolates were the most prevalent species (n = 483; 99.59%). Amphotericin B and the echinocandins demonstrated good in vitro activity against the majority of isolates in comparison to triazole. Overall, 16.15% (n = 78) of isolates were phenotypically resistant to at least one of the azoles. However, 9.73% of A. fumigatus isolates for voriconazole were classified as resistant, 89.03% were susceptible, and 1.24% were intermediate. While, for itraconazole and posaconazole, using the epidemiological cut-off value 16.15% and 6.83% of isolates were non-wild types, respectively. Remarkably, in 21.79% (n = 17) phenotypically resistant isolates, no mutations were detected within the cyp51A gene., Conclusion: Although the incidence of ARAf varies from country to country, in Iran the rate has ranged from 3.3% to 18%, significantly increasing from 2013 to 2021. Strikingly, a quarter of the phenotypically resistant isolates harboured no mutations in the cyp51A gene. It seems that other mechanisms of resistance are importantly increasing. To fill a gap in our understanding of the mechanism for azole resistance in the non-cyp51A strains, we highly recommend further and more extensive monitoring of the soil with or without exposure to fungicides in agricultural and hospital areas., (© 2022 Wiley-VCH GmbH.)

The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38-A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001 μg/ml), followed by anidulafungin (0.104 μg/ml), posaconazole (0.15 μg/ml), itraconazole (0.37 μg/ml), efinaconazole (0.5 μg/ml), voriconazole (0.51 μg/ml), tavaborole (0.72 μg/ml), and amphotericin B (0.79 μg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy., (© 2022 Wiley-VCH GmbH.)

Introduction. Aspergillus sections Flavi and Nigri comprise clinically relevant and cryptic species that differ significantly in drug susceptibility, meaning that effective treatment depends on correct species identification. Hypothesis/Gap Statement. There are no comprehensive data for molecular identification and antifungal susceptibility testing (AFST) of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri as the main agents of invasive and non-invasive aspergillosis in Iran. We aimed to perform molecular identification and AFST of 213 clinical Aspergillus isolates belonging to sections Flavi and Nigri . Molecular identification of isolates was performed using sequencing of the β-tubulin gene and in vitro AFST was conducted according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 guidelines. Results. The most common isolates in sections Flavi and Nigri were Aspergillus flavus (110/113, 97.3 %) and Aspergillus tubingensis (49/100, 49.0 %), respectively. A total of 62/213 (29.1 %) isolates belonging to cryptic species were identified; among them, A. tubingensis was the most prevalent (49/62, 79.0%). Aspergillus flavus and A. niger isolates that responded to the minimum inhibitory concentrations (MICs) of itraconazole above the epidemiological cutoff values were the most frequently detected: 8/110 (7.3 %) and 3/41 (7.3 %), respectively. In section Flavi , Aspergillus alliaceus responded to amphotericin B at a high MIC (>16 µg mL -1 ) and in section Nigri , one of the three Aspergillus luchuensis/awamori isolates responded to itraconazole at an MIC >16 µg ml -1 . Interestingly, for all Aspergillus welwitschiae isolates, the MIC 50 and MIC 90 of itraconazole were both 16 µg ml -1 . Conclusion. A considerable presence of A. flavus and A. niger isolates showing non-wild-type responses to azoles in clinical cases of aspergillosis indicates the importance of classifying clinical Aspergillus isolates at the species level and performing antifungal susceptibility testing on the isolates, which would ensure appropriate treatment.

The fungus genus Neoscytalidium is mainly distributed in (sub) tropical regions of the world and has been essentially considered as a phytopathogen. There are however several reports of human infection caused by Neoscytalidium spp. through direct or indirect contact with contaminated plants or soil. Reliable and accurate identification to species level is critical for implementing proper therapeutic strategies. In the present study we investigated the genotypes and in vitro antifungal susceptibility patterns of Neoscytalidium species identified from respiratory tracts of patients with various underlying diseases. The identity and diversity of the isolates were done using PCR and sequencing of five different loci (the ITS region, D1/D2 domains of 28S rRNA gene, and part of the beta tubulin, elongation factor 1α and chitin synthase genes). The in-vitro antifungal susceptibility was also performed using the Clinical and Laboratory Standards Institute (CLSI) M38-Ed3-2017 guidelines. Overall, 13 isolates were identified as Neoscytalidium species (eight N. dimidiatum and five N. novaehollandiae). Two sequence types (STs) were identified by the alignment of 1846 combined base pairs among 13 clinical isolates. All isolates classified as N. dimidiatum were clustered in ST6 (61.5%) and those of N. novaehollandiae were in ST7 (38.5%). Luliconazole was the most active antifungal in vitro against species. This is the first report of N. novaehollandiae isolation from respiratory tracts samples. Further study from other regions of the world with a larger set of clinical specimens is required to provide additional insight into diversity of Neoscytalidium species., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Onychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated., Methods: In this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts., Results: 594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi., Conclusions: The prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Halvaee, Daie-Ghazvini, Hashemi, Khodavaisy, Rahimi-Foroushani, Bakhshi, Rafat, Ardi, Abastabar, Zareei, Borjian-Boroujeni and Kamali Sarvestani.)

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.

Background: Trichophyton tonsurans is the most common agent causing tinea gladiatorum in wrestlers, and limited data on susceptibility profiles of Trichophyton tonsurans are available., Objectives: We aimed to assess the in vitro activity of the common antifungal drug against a large collection of T tonsurans., Materials/methods: The in vitro activities to eight common antifungal drugs (sertaconazole, itraconazole, clotrimazole, fluconazole, butenafine, tolnaftate, terbinafine and griseofulvin) against 128 clinical isolates of T tonsurans strains, obtained from wrestlers with dermatophytosis, were performed according to CLSI M38-A2 broth microdilution document., Results: The geometric mean minimum inhibitory concentration was the lowest for tolnaftate (0.022 µg/mL), followed by itraconazole (0.026 µg/mL), terbinafine (0.033 µg/mL), butenafine (0.088 µg/mL), griseofulvin (0.566 µg/mL), sertaconazole (2.875 µg/mL), clotrimazole (3.419 µg/mL) and fluconazole (12.540 µg/mL)., Conclusions: Evaluation of antifungal susceptibility of dermatophytes showed that tolnaftate and itraconazole were the most effective drugs against T tonsurans and fluconazole had the least effect., (© 2020 Wiley-VCH GmbH.)

A series of indole-derived methoxylated chalcones were described as anti-dermatophyte agents. The in vitro antifungal susceptibility testing against different dermatophytes revealed that most of compounds had potent activity against the dermatophyte strains. In particular, the 4-ethoxy derivative 4d with MIC values of 0.25-2 μg/ml was the most potent compound against Trichophyton interdigitale, Trichophyton veruccosum and Microsporum fulvum. Moreover, the 4-butoxy analog 4i displaying MIC values in the range of 1-16 μg/ml had the highest inhibitory activity against Trichophyton mentagrophytes, Microsporum canis, and Arthroderma benhamiae. To predict whether the synthesized compounds interact with tubulin binding site of dermatophytes, the 3D-structure of target protein was modeled by homology modeling and then used for molecular docking and molecular dynamics (MD) simulation studies. Docking simulation revealed that the promising compound 4d can properly bind with tubulin. The molecular dynamics analysis showed that interactions of compound 4d with the active site of target protein have binding stability throughout MD simulation. The results of this study could utilize in the design of more effective antifungal drugs with tubulin inhibition mechanism against keratinophilic fungi., Competing Interests: Declaration of Competing Interest The authors report that they have no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction. Limited data regarding the epidemiology and susceptibility profiles of cryptococcosis are available in the Middle East. Aim. Our study aimed to evaluate the molecular diversity, mating types and antifungal susceptibility pattern of Cryptococcus species ( n =14) isolated from 320 suspected patients with cryptococcosis. Methodology. The URA5 gene was subjected to restriction fragment length polymorphism and sequence analysis. In addition, in vitro antifungal susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) M27-A4 and M59 guidelines. Results. Overall, 14 (4.4 %) patients were confirmed as cryptococcosis. Based on molecular type, 85.7 and 14.3 % of the isolates were C. neoformans VN I and VN II, respectively. Phylogenetic analysis of URA5 gene sequences revealed clustering of VN I and VN II isolates into two distinct clades with a substantial difference within each molecular type. Voriconazole and 5-fluorocytosine, respectively, had the lowest (0.031 μg ml -1 ) and highest (8 µg ml -1 ) MICs. The epidemiological cutoff values (ECVs) for amphotericin B, fluconazole, voriconazole and 5-fluorocytosine encompassed ≥97 % of all 14 C . neoformans VN I species. However, according to the CLSI document M59, ECVs for itraconazole (7; 50 % of the isolates) and for posaconazole (1; 7.1 % of the isolate), were one log2 dilution higher than the wild type range. Combinations of amphotericin B with 5-fluorocytosine, amphotericin B with fluconazole and fluconazole with 5-fluorocytosine exhibited synergistic effects against 37, 31 and 12.5 % of the isolates, respectively. Conclusion. Our findings may significantly contribute to the development of management strategies for patients at a higher risk of cryptococcosis, particularly HIV-positive individuals.

Background: Microsporum canis is a zoophilic species, found to be the most frequently isolated species in animals. M. canis causes sporadic outbreaks of infections in humans, such as the one that occurred in Canada, where more than 1000 human cases were detected over an 8-year period. Despite the medical importance of M. canis infections, there are limited in vitro data on the antifungal susceptibility to antifungal drugs, including new generation triazoles and imidazoles., Objective: The aim of the current study was to comprehensively evaluate the in vitro activity of new azoles and comparator drugs against a large panel of M. canis isolates using a microdilution assay., Methods: The in vitro susceptibility to novel triazoles and imidazoles was compared to that of other antifungal drugs using a large collection of M. canis clinical isolates (n = 208) obtained from patients and animals with dermatophytosis in Iran, France and Turkey., Results: All isolates exhibited high susceptibility to the majority of the tested antifungal agents. However, luliconazole, lanoconazole and efinaconazole, as well as econazole, demonstrated superior activity against all strains in comparis on with the other drugs., Conclusion: FDA-approved antifungal drugs, that is luliconazole, efinaconazole and lanoconazole, showed the highest antifungal activity and should be promising candidates for the treatment of dermatophytosis caused by M canis. However, their therapeutic effectiveness remains to be determined in clinical settings., (© 2019 Blackwell Verlag GmbH.)

Aspergillus clavatus is a common environmental species known to cause occupational allergic disease in grain handlers. We have recently observed azole-resistant isolates of this fungus as a cause of onychomycosis. To further characterize the cause of resistance, the genes encoding 14 α-sterol demethylase enzyme ( cyp51A and cyp51B ) were characterized and analyzed in 9 ITC-susceptible isolates and 6 isolates with high minimum inhibitory concentrations (MICs) of clinical (nail and sputum) and environmental A. clavatus strains. We found that six isolates with itraconazole MIC >16 mg/L demonstrated nonsynonymous mutations, including V51I, L378P, E483K, and E506G, and synonymous mutations, including F53F, A186A, Q276Q, and H359H. Moreover, P486S was detected in five strains with ITR MIC >16 mg/L. One mutation, F324S, was detected in an isolate with posaconazole MIC >16 mg/L. The effect of E483K and P486S mutations of CYP51A on azole resistance was further investigated using homology modeling and molecular dynamics. We found that E483K and P486S mutations were located near the ligand access channel of CYP51A that could partly lead to narrowing the entry of the ligand access channels. Therefore, we concluded that E483K and P486S mutations may potentially contribute to the limited access of inhibitors to the binding pocket and therefore confer resistance to azole agents.

Introduction: The incidence of Aspergillus infections has recently increased remarkably in certain tropical and sub-tropical countries, with Aspergillus flavus being identified as the leading cause of infections after A. fumigatus. Lanoconazole (LAN) and luliconazole (LUL) are currently approved for topical treatment of cutaneous fungal infections. We aimed the in-vitro antifungal susceptibility testing of two imidazole, LAN and LUL against A. flavus., Methods: One hundred and eighty-seven clinical and environmental A. flavus were tested originating from different climate zones of Iran between 2008 and 2015. The identification of all isolates was confirmed by using PCR-sequencing of β-tubuline ribosomal DNA gene. In-vitro antifungal susceptibility test was performed using CLSI guidelines against LAN, LUL, itraconazole (ITC), voriconazole (VRC), posaconazole (POS), Isavuconazole (ISA), amphotericin B (AMB), 5-flucytosine (5FC), caspofungin (CAS) and anidulafungin (AFG). The minimum inhibitory concentration (MIC) and minimum effect concentration (MEC) values were evaluated according to CLSI M38-A2 guidelines., Results: The geometric mean MICs for tested antifungals, in increasing order, were: 0.009 μg/mL for LUL (ranging from 0.004 to 0.062), 0.02 μg/mL for LAN (ranging from 0.004 to 0.125), POS (0.10), ISA (0.16), ITC (0.24), VRC (0.27), AMB (1.8) and 5FC (63.06) μg/mL. The mean value of MECs for AFG and CAS were 0.06 and 0.07, respectively., Conclusion: Overall, LUL and LAN showed the lowest MIC against all isolates of A. flavus. Further studies are required to evaluate the in-vivo efficacy of these agents, and the possibility of using these agents in systemic infections., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The in vitro activity of tavaborole, an FDA-approved antifungal drug, was compared to that of four antifungal agents against 170 clinical fungal isolates originating from patients with onychomycosis. Tavaborole had low activity against all isolates compared to itraconazole, terbinafine, and fluconazole, the principal choices for treatment of onychomycosis. Thus, it appears that tavaborole is not a candidate for the treatment of onychomycosis due to Candida species, Aspergillus species, and dermatophytes., (Copyright © 2018 American Society for Microbiology.)

A collection of clinical ( n = 47) and environmental ( n = 79) Fusarium isolates were tested against 10 antifungal drugs, including 2 novel imidazoles. Luliconazole and lanoconazole demonstrated very low geometric mean MIC values of 0.005 and 0.013 μg/ml, respectively, compared with 0.51 μg/ml for micafungin, 0.85 μg/ml for efinaconazole, 1.12 μg/ml for natamycin, 1.18 μg/ml for anidulafungin, 1.31 μg/ml for voriconazole, 1.35 μg/ml for caspofungin, 1.9 μg/ml for amphotericin B, and 4.08 μg/ml for itraconazole. Results show that these drugs are potential candidates for (topical) treatment of skin and nail infections due to Fusarium species., (Copyright © 2018 American Society for Microbiology.)

The objective of this study was to assess the in vitro activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole, and fluconazole) against a large collection of Trichophyton interdigitale and Trichophyton rubrum clinical isolates. The geometric mean MICs were the lowest for luliconazole (0.0005 μg/ml), followed by lanoconazole (0.002 μg/ml), efinaconazole (0.007 μg/ml), terbinafine (0.011 μg/ml), itraconazole (0.095 μg/ml), and fluconazole (12.77 μg/ml). It appears that efinaconazole, lanoconazole, and luliconazole are promising candidates for the treatment of dermatophytosis due to T. interdigitale and T. rubrum ., (Copyright © 2018 American Society for Microbiology.)

Aspergillus fumigatus is the leading cause of mortality in severely immunocompromised individuals. Understanding pathogen dispersion and relatedness is essential for determining the epidemiology of nosocomial infections. Therefore, the aim of this study was to investigate the diversity and putative origins of clinical and environmental azole-susceptible and -resistant A. fumigatus isolates from Iran. In all, 79 isolates, including 64 azole-susceptible and 15 -resistant isolates, were genotyped using the cell surface protein (CSP) gene. Seven distinct repeat types (r01, r02, r03, r04, r05, r06 and r07) and 11 different CSP variants (t01, t02, t03, t04A, t06A, t06B, t08, t10, t18A, t18B and t22) were observed. Interestingly, t06B, t18A and t18B were exclusively present in azole-resistant isolates. The Simpson's index of diversity (D) was calculated at 0.78. Resistant isolates were genetically less diverse than azole-susceptible isolates. However, azole-resistant A. fumigatus without TR 34 /L98H were more diverse than with TR 34 /L98H. The limited CSP type diversity of the TR 34 /L98H isolates versus azole-susceptible isolates suggests that repeated independent emergence of the TR 34 /L98H mechanism is unlikely. It has been suggested that CSP types might have a common ancestor that developed locally and subsequently migrated worldwide., (© 2017 Blackwell Verlag GmbH.)

A collection of azole-susceptible (n = 141) and azole-resistant (n = 27) Aspergillus fumigatus isolates was tested against seven antifungal drugs, including the new imidazoles lanoconazole and luliconazole. The luliconazole and lanoconazole MIC 90 values for the azole-susceptible strains were 0.001 μg/ml and 0.008 μg/ml, and those for the azole-resistant strains were 0.016 μg/ml and 0.032 μg/ml., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

In vitro susceptibilities of 100 clinical dermatophyte isolates belonging to five species from Iran toward lanoconazole and luliconazole were compared with ten other antifungal agents including econazole, itraconazole, miconazole, fluconazole, griseofulvin, butenafine, terbinafine, caspofungin, anidulafungin and tolnaftate. MIC and MEC values were analyzed according to CLSI M38-A2 document. The isolates were previously identified to the species level using PCR-RFLP on ITS rDNA region. The range of luliconazole and lanoconazole minimum inhibitory concentrations (MICs) was 0.016-0.032 and 0.063-1 μg/ml, respectively for dermatophyte species. Luliconazole and lanoconazole revealed potent activity against all dermatophyte isolates. Anidulafungin, caspofungin, and luliconazole showed the best activity with the lowest geometric mean 0.01, 0.016, and 0.018 μg/ml, respectively, followed by tolnaftate (0.06 μg/ml), terbinafine (0.07 μg/ml), itraconazole (0.183 μg/ml), butenafine (0.188 μg/ml), econazole (0.20 μg/ml), lanoconazole (0.24 μg/ml), griseofulvin (1.28 μg/ml), miconazole (2.34 μg/ml) and fluconazole (15.34 μg/ml). The current study demonstrated luliconazole and lanoconazole displayed excellent activity against all dermatophyte isolates, although the majority of dermatophyte isolates showed low susceptibility to griseofulvin and very low to miconazole, and fluconazole., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Onychomycosis is a common fungal infection of nails which is mainly caused by dermatophyte species and less often by yeasts and non-dermatophyte molds. We present a case of onychomycosis due to Aspergillus clavatus for the first time worldwide. The patient was an immunocompetent 32-year-old woman who identified with Psoriasis of the nail. The presence of A. clavatus in a nail sample was confirmed using microscopic and culture analysis followed by PCR of the β-tubulin gene. After antifungal susceptibility test, it is revealed that the isolate was resistant to the majority of common antifungal drugs, but finally the patient was treated with itraconazole 200 mg daily. A. clavatus and drug-resistant A. clavatus have not previously been reported from onychomycosis.

Introduction: Wrestling, considered the national sport of Iran, has gained immense popularity among Iranians. Wrestlers frequently encounter skin conditions, with dermatophyte fungal infections, particularly tinea gladiatorum (TG), being a common issue. TG, caused by the Trichophyton genus, has emerged as a major health concern for wrestlers and other contact sport athletes worldwide. This study aimed to assess the genotypic diversity and antifungal susceptibility of Trichophyton tonsurans isolates responsible for TG in Iranian wrestlers from Mazandaran province, northern Iran. Materials and Methods: A total of 60 clinical T. tonsurans isolates collected from various cities in Mazandaran, were included in the study. The isolates were identified through PCR-restriction fragment length polymorphism and sequencing methods. Genomic DNA was extracted from these isolates, and the non-transcribed spacer (NTS) region of ribosomal RNA (rRNA) was targeted for genotyping using newly designed primers. Haplotype analysis was performed to explore genetic diversity, and antifungal susceptibility to terbinafine (TRB) and itraconazole (ITC) was assessed. Results: The results revealed five distinct NTS types: NTS-I, NTS-II, NTS-III, NTS-IV and NTS-V, with NTS-IV being the most prevalent. The distribution of NTS types varied across different cities, suggesting potential transmission patterns among wrestlers. Antifungal susceptibility testing showed that all isolates were susceptible to TRB, while one isolate demonstrated resistance to ITC. Genotypic diversity was not correlated with antifungal susceptibility, emphasising the importance of monitoring susceptibility to ensure effective treatment. Haplotype analysis highlighted significant genetic diversity among the T. tonsurans isolates. This diversity may be attributed to factors such as human-to-human transmission, geographic location and lifestyle changes. The study's findings underscore the need for comprehensive genotypic analysis to understand the epidemiology and evolution of T. tonsurans infections in athletes. Conclusion: In conclusion, this study provides valuable insights into the genotypic diversity and antifungal susceptibility of T. tonsurans isolates causing TG in Iranian wrestlers. The presence of multiple NTS types and varying susceptibility patterns highlights the complexity of T. tonsurans infections in this population. Further research is warranted to track the transmission routes and genetic evolution of T. tonsurans strains among wrestlers and develop effective control measures. [ABSTRACT FROM AUTHOR]

Objective: Opportunistic fungal infections by Candida species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal agents have developed the resistance of Candida spp. to antifungals. Accurate identification of yeasts and susceptibility patterns are main concerns that can directly effect on the treatment of patients. Methods: Over a period of three years, 325 cancer patients suspected to Candida infections were included in the current investigation. The clinical isolates were molecularly identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All strains, were examined for in vitro susceptibility to the amphotericin B, itraconazole, fluconazole, and anidulafungin according to the CLSI M27 document. Results: Seventy-four cancer patients had Candida infections (22.7%). Candida albicans was the most common species (83.8%). Antifungal susceptibility results indicated that 100% of the Candida isolates were sensitive to amphotericin B; however, 17.6%, 9.4%, and 5.4% of clinical isolates were resistant to anidulafungin, fluconazole, and itraconazole, respectively. Conclusion: The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection. [ABSTRACT FROM AUTHOR]

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063–0.5 µg/mL and 0.125–0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy. [ABSTRACT FROM AUTHOR]

Background: Fusarium species are opportunistic human pathogens that remarkably cause fungal infections ranging from superficial to fatal invasive disseminated infections. Fusarium species are notoriously resistant to the majority of antifungal agents. Objectives: Therefore, detailed studies regarding in vitro susceptibility are required and may lead to a better prognosis of severe infections. Methods: We evaluated 25 antifungal drugs in vitro against 282 clinical and environmental Fusarium isolates. Results: Fusarium species demonstrated high MICs/MECs values to the most commonly used antifungal drugs in clinical practice. The geometric mean (GM) MICs for luliconazole (0.004 μg/ml) and lanoconazole (0.012 μg/ml) were the lowest, followed by efinaconazole (0.98 μg/ml) and amphotericin B (1.04 μg/ml). Conclusions: Efinaconazole, a novel triazole, may be a promising candidate for the treatment of superficial Fusarium infections. Furthermore, the development of systemic formulations of these drugs as well as further in vitro and in vivo investigations could aid in the treatment of systemic fusariosis. [ABSTRACT FROM AUTHOR]

Background: Otomycosis is considered a recurring fungal ear infection. The external auditory canal provides an appropriate and optimal situation for fungal growth. Objectives: The study aimed to identify the causative agents of otomycosis and determine corresponding antifungal drug susceptibility patterns in north‐western Iran. Methods: From October 2020 until November 2021, 200 patients attended an otolaryngology referral centre with otitis externa, and their ear discharge and debris were examined and cultured. The identification of the fungal agents was implemented by polymerase chain reaction‐restriction fragment length polymorphism and sequencing. In vitro antifungal susceptibility testing of the isolates was conducted in accordance with the CLSI broth microdilution protocols. Results: The prevalence of otomycosis was measured 50.5% (n = 101/200). The majority of patients were in their forties (n = 35, 34.6%) and female (n = 57, 56.4%), and the most prevalent symptom was otalgia (56.4%). The most underlying factor was remarked manipulation employing a cotton swab (65.3%). Regarding fungus, Aspergillus section Nigri (58.57%) was the foremost isolate, followed by Aspergillus section Flavi (19.23%) and Candida parapsilosis (14.96%). The predominance of Aspergillus isolates had minimal in vitro sensitivity to tioconazole and nystatin. Candida species represented higher geometric mean minimum inhibitory concentrations (MIC) against nystatin. The MIC of three Aspergillus species isolates shown above the epidemiologic cut‐off values (ECV) against itraconazole. Conclusions: Otomycosis incidence surpassed in comparison with the previous study as the most common cause of otitis externa. The MIC distribution of Aspergillus species isolates against triazole antifungals is close to the defined ECVs and likely outrun it over time. [ABSTRACT FROM AUTHOR]

Introduction: Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open‐source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents. Materials and methods: Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole. Results: Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008–2 µg/ml, 0.001–0.064 µg/ml and 0.001–0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles. Conclusion: The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma. [ABSTRACT FROM AUTHOR]

Background: Opportunistic infections due to Candida species occur frequently in cancer patients because of their inherent immunosuppression. The aim of the present study was to investigate the epidemiology of yeast species from the oral cavity of patients during treatment for oncological and haematological malignancies.Methods: MALDI-TOF was performed to identify yeasts isolated from the oral cavity of 350 cancer patients. Moreover, antifungal susceptibility testing was performed in according to CLSI guidelines (M27-A3).Results: Among 162 yeasts and yeast-like fungi isolated from the oral cavity of cancer patients, Candida albicans was the most common species (50.6%), followed by Candida glabrata (24.7%), Pichia kudriavzevii (Candida krusei (9.9%)), Candida tropicalis (4.3%), Candida dubliniensis (3.7%), Kluyveromyces marxianus (Candida kefyr (3.7%)) and Candida parapsilosis (1%). In addition, uncommon yeast species i.e., Saprochaete capitata, Saccharomyces cerevisiae, Clavispora lusitaniae (C. lusitaniae) and Pichia kluyveri (C. eremophila) were recovered from oral lesions. Oral colonization by C. albicans, non-albicans Candida species and uncommon yeasts were as follow; 55%, 44% and 1%, whereas oral infection due to C. albicans was 33.3%, non-albicans Candida species 60.6%, and uncommon yeasts 6.1%. Poor oral hygiene and xerostomia were identified as independent risk factors associated with oral yeast colonization. The overall resistance to fluconazole was 11.7% (19/162). Low MIC values were observed for anidulafungin for all Candida and uncommon yeast species.Conclusions: This current study provides insight into the prevalence and susceptibility profiles of Candida species, including emerging Candida species and uncommon yeasts, isolated from the oral cavity of Iranian cancer patients. The incidence of oral candidiasis was higher amongst patients with hematological malignancies. The majority of oral infections were caused by non-albicans Candida species which were often more resistant to anti-fungal agents. Our findings suggest that anidulafungin should be used as antifungal of choice for prophylaxis in clinically high-risk patients with documented oral colonization or infection. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is one of the most important agents of invasive and non-invasive aspergillosis, especially in tropical and subtropical regions of the world, including Iran. Aspergillus oryzae is closely related to A. flavus, and it is known for its economic importance in traditional fermentation industries. Reports of infection due to A. oryzae are scarce. Several studies reported that differentiating these two species in clinical laboratories is not possible using MALDI-TOF or by targeting fungal barcode genes, such as Internal Transcribed Spacer (ITS) and β-tubulin (benA). The species-level identification of causative agents and the determination of antifungal susceptibility patterns can play significant roles in the outcome of aspergillosis. Here, we aimed to investigate the discriminatory potential of cyp51A PCR-sequencing versus that of the ITS, benA and calmodulin (CaM) genes for the differentiation of A. flavus from A. oryzae. In a prospective study investigating the molecular epidemiology of A. flavus in Iran between 2008 and 2018, out of 200 clinical isolates of A. flavus, 10 isolates showed >99% similarity to both A. flavus and A. oryzae. Overall, the ITS, β-tubulin and CaM genes did not fulfil the criteria for differentiating these 10 isolates. However, the cyp51A gene showed promising results, which warrants further studies using a larger set of isolates from more diverse epidemiological regions of the world. [ABSTRACT FROM AUTHOR]

An essential oil derived from the evergreen plant Thymus vulgaris acts as an antifungal agent with strong antimicrobial activity, but it has low water solubility. The current study therefore aimed to enhance the solubility of thyme essential oil by formulating it into a nanoemulsion and investigating its effectiveness on a broad range of fungi. The identification of the compositions of essential oils was performed using GC–MS. Thyme essential oil nanoemulsion (TV EO-NE) was prepared by using a high-pressure homogenization method. Both viability and cytotoxicity outcomes on Human fetal foreskin fibroblast cells were gauged by different concentrations of Thymus vulgaris essential oils and TV EO-NE after 24 and 48 h. Antifungal susceptibility tests were carried out based on the modified CLSI M60 document for yeasts and CLSI M28-A3 documents for filamentous fungi. Thyme essential oil was mainly composed of thymol (22.10 %), p-cymene (21.31 %), carvacrol (13.02 %), carvacrol acetate (6.72 %), and linalool (5.58 %). The TV EO-NEs were spherical with a mean diameter of 127.6 ± 62.52 nm and zeta potential of −9.82 ± 6.07 mV. The MIC90 for C. albicans and C. glabrata isolates was 0.031 μg/mL and 0.0625 μg/mL for C. parapsilosis. Also, MIC90 for both dermatophytes and Aspergillus fumigatus isolates was determined to be 0.016 μg/mL. For yeasts and filamentous fungi, a significant reduction in MIC values was observed using TV EO-NE (p < 0.05). The study highlighted T. vulgaris and thymol to be promising alternatives for the treatment of cutaneous mycoses especially when the etiological agents are resistant to conventional antifungal drugs. [ABSTRACT FROM AUTHOR]

Abstract In this present study, for the first time, we evaluated the cystic fibrosis (CF) patients for the Scedosporium species and their antifungal susceptibility against eight antifungal agents. During one-year period, 90 Sputum samples were collected from Iranian CF patients. All samples were evaluated by direct microscopic examination, culture onto four different media including Malt extract agar, Inhibitory mold agar, Brain Heart Infusion and Scedo-Select III. The mold isolated fungi were identified by PCR-Sequencing of ITS and β-tubulin genes. In-vitro antifungal susceptibility was performed according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 guidelines. Out of 90 CF patients, 47 (52.2%) were male. The age of the patients ranged from 1 to 34 years (median of 15.84 ± 7.41 years). Overall, 3 (3.3%) cases were positive for Scedosporium spp. of which two isolates were characterized as Scedosporium boydii and one isolate as S. ellipsoideum. Among Aspergillus genus, A. flavus (29.4%) was the most prevalent species followed by A. tubingensis (24.7%), A. niger (17.0%) and A. fumigatus (14.5%). The minimum effective concentration ranges of micafungin, anidulafungin, and caspofungin were 0.008–0.031 μg/mL, 0.0625–0.25 μg/mL, and 0.0625–0.25 μg/mL, respectively. All isolates of Scedosporium species showed high minimum inhibitory concentration to the triazoles tested, except voriconazole. Our results showed that A. flavus and Scedosporium species are the most prevalent molds isolated from CF patient populations in Iran. Our findings have also showed that Scedo-Select III can be used as a reliable culture media for isolation of Scedosporium spp. in clinical samples. Highlights • The prevalence of Scedosporium species In Iranian patients with cystic fibrosis was 3.3%. • A. flavus was the most common species within the Aspergillus genus. • Scedo-Select III can optimize the growth of Scedosporium species within a mixed samples. • Scedosporium species showed an increased MIC against the main antifungal agents. [ABSTRACT FROM AUTHOR]