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This case report describes the progressive wound infection in the left thigh of a 34-year-old man due to an old landmine explosion. The infection developed into rapidly spreading skin and soft tissue necrotising Saksenaea infection, despite antifungal therapy and surgical debridement. The report provides evidence that Saksenaea spp. should be added to the list of mucoralean fungi that can cause severe necrotising infection. It also highlights the need for improved early diagnostic procedures and enhanced understanding of Saksenaea virulence factors that contribute to necrotising infection.

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31

INTRODUCTION: Agricultural commodities contaminated by molds and mycotoxins can be considered as public health problems in less developed countries, particularly in Iran. Hence the main purpose of this study was to identify mold fungi and molecular analysis of the most important species of aflatoxin-B1-producing Aspergillus species in some dried nuts and grains in local markets in Tehran. MATERIALS AND METHODS: Two hundred fifty samples of wheat, rice, corn, pistachios, and peanuts were collected from the five different locations of Tehran between January 2018 and January 2019. The samples were analyzed by using direct seed inoculation method and grain crushing method. Fungal strains were identified as Aspergillus spp. on the basis of morphological characters and further confirmed by using of β-tubulin gene sequencing. To differentiate between aflatoxigenic and non-aflatoxigenic Aspergillus spp., the isolates were screened for the presence of aflatoxigenic genes (nor-1, ver-1, omtA, and aflR). RESULTS: One-handed forty-eight aflatoxigenic Aspergillus isolates (144 A. flavus and 4 A. parasiticus) were identified and aflR gene was the most frequent gene in these species. Five isolates (4 A. flavus, 1 A. parasiticus) had quadruplet pattern, 64 isolates (63 A. flavus, 1 A. parasiticus) had more than 1 gene and 39 isolates (38 A. flavus,1 A. parasiticus) did not have any genes. CONCLUSION: According to the contamination of dried nuts and grains by some aflatoxigenic fungi, an extensive surveillance is necessary to provide a wider view on these products. Moreover, effective and efficient aflatoxin control program requires identifying and managing key elements that are effective in reducing mycotoxin production at farm level or in storage conditions.

Candida parapsilosis is one of the main emerging non-Candida albicans species leading to superficial and systemic fungal infections in humans. Candida has the ability to produce biofilms associated with pathogenesis. The aim of the study was to estimate biofilm-producing ability of clinical isolates of C. parapsilosis sp. complex.Clinical samples of C. parapsilosis complex have been analyzed. Crystal violet (CV) staining and tetrazolium reduction assay (MTT) have been used to analyze the clinical isolates ability to produce biofilms. The biofilm's structural characteristics have been assessed by using scanning electron microscopy.All 65 isolates were able to form biofilm. In addition, no significant difference was found between biofilm quantification based on two assays at different time intervals (24h, 48h, 72h, 96h) (P0.05), with the exception of Candida orthopsilosis, which exhibited higher metabolic activity at 24h time point (P0.05). Moreover, metabolic activity and production of biofilm biomass demonstrated statistically significant correlation (r=0.685, P0.01). According to microscopic observations, the investigated clinical strains formed the similar surface topography with the slight differences in morphology; in addition, there was no statistically significant difference between efficiency of two assays to quantify biofilm.It was shown that, similar to C. parapsilosissensu stricto, two cryptic identified species (C. orthopsilosis and Candida metapsilosis) obtained from different clinical samples, were biofilm producers, while C. parapsilosissensu stricto exhibited the highest biofilm production.

This case report describes the progressive wound infection in the left thigh of a 34-year-old man due to an old landmine explosion. The infection developed into rapidly spreading skin and soft tissue necrotising

Background Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases despite the commencement of antifungal therapy. We investigated the molecular epidemiology, clinical characteristics, comorbidity risk factors, species distribution, antifungal susceptibility profile, and outcome of candidemia to provide appropriate perspectives in Tehran, Iran. Methods A prospective observational study of all patients diagnosed with candidemia was performed at two referral teaching hospitals in Tehran. Demographic characteristics, underlying diseases, risk factors, clinical symptoms, and laboratory analyses were mined. Results One-hundred and fifty-two Candida isolates from 89 patients with candidemia were recovered. The overall crude mortality was 47.2%. The most common underlying disease was sepsis (48.3%) followed by malignancy (46.1%), renal failure/ dialysis (43.8%), and Hypertension (40.0%). C. albicans (43.8%) was the most frequent causative agent followed by C. glabrata (21.3%), C. parapsilosis complex (15.7%), C. tropicalis (11.2%), and C. lusitaniae (3.4%). Result of antifungal susceptibility test show that activity of all the four azole antifungal agents was low against non-albicans Candida species, especially C. tropicalis. Conclusion Increase in non-albicans Candida species with reduced susceptibility to antifungal drugs might be alarming in high-risk patients. Therefore, accurate knowledge of predisposing factors and epidemiological patterns in candidemia are effective steps for managing and decreasing the mortality rate in candidemia.

Introduction Candida parapsilosis (C. parapsilosis) is a common non-albicans Candida species ranked as the second common cause of bloodstream infections. Azole resistance and elevated echinocandin MICs have been reported for these fungi. This study was conducted to determine the interactions between azoles and echinocandins against C. parapsilosis species complex. Materials and methods Fifteen fluconazole-resistant clinical isolates of C. parapsilosis complex were included: C. parapsilosis sensu stricto (n = 7), C. orthopsilosis (n = 5) and C. metapsilosis (n = 3). The activity of azoles (fluconazole, itraconazole) and echinocandins (anidulafungin, micafungin) alone and in combination was determined using checkerboard broth microdilution. The results were determined based on the fractional inhibitory concentration index (FICI). Results In vitro combination of fluconazole with anidulafungin was found to be synergistic (FICI 0.07–0.37) and decreased the MIC range from 4–64 μg/mL to 0.5–16 μg/mL for fluconazole and from 2–8 μg/mL to 0.125–1 μg/mL for anidulafungin. Similarly, interactions of fluconazole with micafungin (FICI 0.25–0.5), itraconazole with anidulafungin (FICI 0.15–0.37) and itraconazole with micafungin (FICI 0.09–0.37) were synergistic. Conclusion The combination of fluconazole and itraconazole with either anidulafungin or micafungin demonstrated synergistic interactions against C. parapsilosis species complex, especially against isolates with elevated MIC values. However, the use of these combinations in clinical practice and the clinical relevance of in vitro combination results remain unclear.

Agricultural commodities contaminated by molds and mycotoxins can be considered as public health problems in less developed countries, particularly in Iran. Hence the main purpose of this study was to identify mold fungi and molecular analysis of the most important species of aflatoxin-B1-producingTwo hundred fifty samples of wheat, rice, corn, pistachios, and peanuts were collected from the five different locations of Tehran between January 2018 and January 2019. The samples were analyzed by using direct seed inoculation method and grain crushing method. Fungal strains were identified asOne-handed forty-eight aflatoxigenicAccording to the contamination of dried nuts and grains by some aflatoxigenic fungi, an extensive surveillance is necessary to provide a wider view on these products. Moreover, effective and efficient aflatoxin control program requires identifying and managing key elements that are effective in reducing mycotoxin production at farm level or in storage conditions.

Background and Purpose: Aspergillosis is one of the most common opportunistic fungal infections in immunocompromised and neutropenic patients. Aspergillus fumigatus (A. fumigatus) is the most common causative agent of this infection. Due to variable CO2 concentrations that pathogens are exposed to during the infection process and to understand the role of CO2, we examined the effects of various CO2 concentrations as one of the environmental factors on morphological changes and induction of antifungal resistance in A. fumigatus. Materials and Methods: A. fumigatus strains were cultured and incubated under 1%, 3%, 5%, and 12% CO2 atmospheres, each time for one, two, and four weeks. The control culture was maintained for one week without CO2 atmosphere. Morphological changes were investigated and antifungal susceptibility test was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The results of different CO2 atmospheres were compared with that of the control sample. Results: We found that 1%, 3%, 5%, and 12% CO2 atmospheres were associated with morphological colony changes. Macroscopically, the colonies were shallow dark green, smooth, crisp to powdery with reduced growth; microscopic examination revealed the absence of conidiation. The induction of antifungal resistance in the susceptible strains to itraconazole, voriconazole, and amphotericin B increased after exposure to 12% CO2 atmosphere and four weeks of incubation. The MIC values for itraconazole, voriconazole, and amphotericin B were 16 g/ml, 1 g/ml, and 16 g/ml, respectively. These values for the control group were 0.125 g/ml, 0.125 g/ml, and 2 g/ml, respectively. Conclusion: Exposure to different CO2 atmospheres induced morphological changes in A. fumigatus, it seems to increase the MIC values, as well. In parallel, resistance to both itraconazole and voriconazole was also observed.

Objective Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis. Material and methods A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document. Results In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range = 0.0005–0.004 μg/mL), while fluconazole (MIC range = 0.4–64 μg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008 μg/mL), followed by lanoconazole (0.003 μg/mL), terbinafine (0.019 μg/mL), itraconazole (0.085 μg/mL), ketoconazole (0.089 μg/mL), econazole (0.097 μg/mL), griseofulvin (0.351 μg/mL), voriconazole (0.583 μg/mL) and fluconazole (11.58 μg/mL). Conclusion The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.

Background and Purpose: Formation of pseudohyphae is considered a virulence factor in Candida species. Generally, Candida glabrata grows as budding yeast cells; however, reports illustrated that C. glabrata could form pseudohyphal cells in response to some stimuli. In this study, we provided insight into the ability of C. glabrata in forming pseudohyphal cells under different levels of carbon dioxide (CO2). Materials and Methods: Candida glabrata reference strain (ATCC 90030) was used in this study. Yeast samples were cultured on Sabouraud dextrose broth (SDB) medium and incubated under 3%, 5%, and 10% CO2 levels for 24, 48 and72h.Control cultures were prepared without CO2 pressure for three days. The possibility of pseudohyphae and mycelium formation in C. glabrata was investigated. Results: The results of this study revealed that the most branching filament-like cells were obtained at high CO2 pressure (10%) after 72 h. After three days of low CO2 pressure (3%), only yeast and budding cells were observed without any pseudohyphae formation. Conclusion: CO2 could act as a stimulus and induced formation of pseudohyphae in Candida glabrata yeast cells. &nbsp

Aspergillus flavus is the second leading cause of invasive and non-invasive aspergillosis, as well as the most common cause of fungal sinusitis, cutaneous infections, and endophthalmitis in tropical countries. Since resistance to antifungal agents has been observed in patients, susceptibility testing is helpful in defining the activity spectrum of antifungals and determining the appropriate drug for treatment. A collection of 199 clinical and environmental strains of Aspergillus flavus consisted of clinical (n=171) and environmental (n=28) were verified by DNA sequencing of the partial b-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MEC of caspofungin were determined in accordance with the Clinical and Laboratory Standards Institute M38-A2 document. Caspofungin, followed by posaconazole, exhibited the lowest minimum inhibitory concentrations (MIC). All isolates had caspofungin MEC90 (0.063μg/ml) lower than the epidemiologic cutoff values, and 3.5% of the isolates had amphotericin B MIC higher than the epidemiologic cutoff values. However, their clinical effectiveness in the treatment of A. flavus infection remains to be determined.

Objective Candida parapsilosis species complex, an important set of non-albicans Candida species, is known to cause candidaemia particularly in neonates and infants. However, the incidence has increased in recent years, owing to higher numbers of at individuals at risk for these infections. Our objective was to evaluate the in vitro susceptibility of clinical isolates of C. parapsilosis complex isolates from Iran to seven antifungal drugs. Material and methods One hundred-one clinical isolates of C. parapsilosis species complex cultured from humans were included. Species identification had been previously confirmed by combined phenotypic characteristics, matrix-assisted laser desorption ionization-time of flight mass spectrometry-based assay and reconfirmed by DNA sequence analysis of the ITS rDNA region and D1/D2 gene. Minimum inhibitory concentrations (MICs) for amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, micafungin and anidulafungin were determined against well-characterized isolates by broth microdilution susceptibility testing according to the CLSI M27-A3 guideline. Results Species identifications were performed on 101 isolates, of which 88 (87.2%) C. parapsilosis sensu stricto and 13 (12.8%) C. orthopsilosis. Amphotericin B and posaconazole were the most active drugs with 100% of isolates being wild-type (WT). Voriconazole and micafungin, 99% of isolates were WT. The low activity was recorded for fluconazole and itraconazole with 93.1% and 89.1% of isolates being WT, respectively. At the species level, all Candida parapsilosis sensu stricto isolates were WT to amphotericin B and posaconazole and all Candida orthopsilosis isolates were WT to amphotericin B, voriconazole, posaconazole, anidulafungin and micafungin. In contrast, the highest rate of non-WT was observed in C. orthopsilosis to itraconazole (4 of 13, 30.8%). Conclusions Although almost all of the tested drugs demonstrated potent activity against C. parapsilosis species complex, it seems that more especially C. orthopsilosis isolates had decreased susceptibility to itraconazole. Further studies are needed to determine how these findings may switch into in vivo efficacy.

Echinococcosis is a zoonotic disease caused by Echinococcus granulosus sensu lato. The liver and lungs are the most commonly sites of infections, but involvements of other organs were also observed. Recently, the coinfection of pulmonary hydatid cyst with aspergilloma has been reported in the literature. Herein, we report a successful treatment of coinfection of cystic echinoccosis with aspergilloma due to Aspergillus flavus in a 34-year-old female. In vitro antifungal susceptibility tests revealed that the MIC values for antifungals employed in this case were posaconazole (0.031μg/ml), itraconazole (0.125μg/ml), voriconazole (0.25μg/ml), and amphotericin B (1μg/ml). The minimum effective concentration for caspofungin was 0.008μg/ml. This coexistence of active pulmonary echinococcosis and aspergillosis is being reported because of its rarity and clinical importance for its management.

Background: Aflatoxins are highly toxic secondary metabolites mainly produced by Aspergillus parasiticus. This species can contaminate a wide range of agricultural commodities, including cereals, peanuts, and crops in the field. In recent years, research on medicinal herbs, such as Pistacia atlantica subsp. kurdica, have led to reduced microbial growth, and these herbs also have a particular effect on the production of aflatoxins as carcinogenic compounds. Objectives: In this study, we to examine P. atlantica subsp. kurdica as a natural compound used to inhibit the growth of A. parasiticus and to act as an anti-mycotoxin. Materials and Methods: In vitro antifungal susceptibility testing of P. atlantica subsp. kurdica for A. parasiticus was performed according to CLSI document M38-A2. The rate of aflatoxin production was determined using the HPLC technique after exposure to different concentrations (62.5 - 125 mg/mL) of the gum. The changes in expression levels of the aflR gene were analyzed with a quantitative real-time PCR assay. Results: The results showed that P. atlantica subsp. kurdica can inhibit A. parasiticus growth at a concentration of 125 mg/mL. HPLC results revealed a significant decrease in aflatoxin production with 125 mg/mL of P. atlantica subsp. kurdica, and AFL-B1 production was entirely inhibited. Based on quantitative real-time PCR results, the rate of aflR gene expression was significantly decreased after treatment with P. atlantica subsp. kurdica. Conclusions: Pistacia atlantica subsp. kurdica has anti-toxic properties in addition to an inhibitory effect on A. parasiticus growth, and is able to decrease aflatoxin production effectively in a dose-dependent manner. Therefore, this herbal extract maybe considered a potential anti-mycotoxin agent in medicine or industrial agriculture.

Aspergillus flavus is the second most important Aspergillus species causing human infections in tropical countries. Despite an increasing number of infections of A. flavus in Iran, the molecular epidemiology of clinical and environmental strains has not been well studied. We used a panel of nine microsatellite markers to analyse the genetic relatedness of A. flavus. Microsatellite typing of 143 (n = 119 clinical and n = 24 environmental) isolates demonstrated 118 different genotypes. A possible outbreak at a pulmonary ward was discovered. The discriminatory power for the individual markers ranged from 0.4812 to 0.9457 and the panel of all nine markers combined yielded a diversity index of 0.9948. This high-resolution typing method assists in better understanding of the molecular epidemiology of A. flavus.

Aims. Biofilms formed byCandidaspecies which associated with drastically enhanced resistance against most antimicrobial agents. The aim of this study was to identify and determine the antifungal susceptibility pattern ofCandidaspecies isolated from endotracheal tubes from ICU patients.Methods. One hundred forty ICU patients with tracheal tubes who were intubated and mechanically ventilated were surveyed for endotracheal tube biofilms. Samples were processed for quantitative microbial culture. Yeast isolates were identified to the species level based on morphological characteristics and their identity was confirmed by PCR-RFLP. Antifungal susceptibility testing was determined according to CLSI document (M27-A3).Results.Ninety-five strains ofCandidawere obtained from endotracheal tubes of whichC. albicans(n=34; 35.7%) was the most frequently isolated species followed by other species which includedC. glabrata(n=24; 25.2%),C. parapsilosis(n=16; 16.8%),C. tropicalis(n=12; 12.6%), andC. krusei(n=9; 9.4%). The resulting MIC90for allCandidaspecies were in increasing order as follows: caspofungin (0.5 μg/mL); amphotericin B (2 μg/mL); voriconazole (8.8 μg/mL); itraconazole (16 μg/mL); and fluconazole (64 μg/mL).Conclusion.Candidaspecies recovered from endotracheal tube are the most susceptible to caspofungin.

Dermatophytes are a group of fungi able to invade keratinized tissues of humans and animals, causing dermatomycosis. Azole antifungal drugs are commonly used in the treatment of dermatomycosis. However, this group of chemicals is known to cause side effects in patients and due to increased use of these medications, azoles are known to cause drug resistance. Having said this, the purpose of the present study was to investigate an alternative anti dermatophyte which is plant based. In this study, allicin, which is a pure bioactive compound isolated from garlic, was tested for its potential as a treatment of dermatomycosis. The study evaluated the in vitro efficacy of pure allicin used alone against ten isolates of Trichophyton rubrum and it was found that the MIC50 and MIC90 ranged from 0.78–25.0 μg/ml, whereas the MIC values for ketoconazole and fluconazole ranged from 0.25–8.0 and 1.0–32.0 μg/ml, respectively, at 28°C for both 7 and 10 days incubation. On the other hand, time–kill studies revealed that the antifungicidal effect of allicin became active within 12–24 h of management in vitro and that it was as good as that of ketoconazole. Finally, most of the tested drug combinations demonstrated synergistic or additive interactions for all isolates for both 7 and 10 days incubation at 28°C. In conclusion, when used alone, allicin showed very good potential as an antifungal compound against mycoses-causing dermatophytes, performing better than the synthetic drug fluconazole and almost as good as ketoconazole. Furthermore, allicin in combination with ketoconazole or with fluconazole frequently showed synergistic or additive interactions against dermatomycosis.

Different studies illustrated that Trichophyton rubrum, among all species of Trichophyton, is the most prevalent and consequently the most important genus. T. rubrum as a worldwide filamentous pathogen fungus can infect human keratinized tissue (skin, nails and rarely hair), and causes dermatophytosis. Researchers use two general methods for the identification of dermatophytes namely, conventional methods on the basis of phenotype variations and molecular methods on the basis of molecular differences. Due to some limitations in traditional methods, in the recent years, molecular biological methods are regarded as useful in the exact and rapid recognition of dermatophytes. The present study identified nine clinical isolates and one ATCC as a control strain of T. rubrum by using both conventional and molecular methods. The molecular systematics method was used to elucidate genetic diversity among strains of T. rubrum and withinTrichophyton species. Morphological characteristics of all colonies T. rubrum quite varies among each other; we revealed that that conventional methods are generally prolonged and may be indecisive. However, molecular studies based on internal transcribed spacer(ITS) sequencing provides a very accurate result, which is more than 96% the similarity ofT. rubrum among all isolates, and more than 90% similarity within Trichophyton spp. Key words: Trichophyton rubrum, conventional method, internal transcribed spacer (ITS) regions, identification, dermatophytes.

Dermatophytosis is caused by a group of pathogenic fungi namely, dermatophytes, is among the most prevalent infectious diseases worldwide. Azole drugs are widely used in the treatment of dermatomycosis, but can cause various side effects and drug resistance to the patients. Hence, for solving this problem can be used from the plant extract as alternative for chemical drugs. Allicin is a pure bioactive compound isolated from garlic was tested for its potential as a treatment of dermatomycosis in this study. This study evaluated the in vitro efficacy of pure allicin against ten isolates of Trichophyton rubrum and the MIC50 and MIC90 ranged from 0.78-12.5 µg/ml for allicin. The results revealed that the order of efficacy based on the MICs values, all isolates showed almost comparable response to allicin and ketoconazole except for some isolates, at 28 ºC for both 7 and 10 days incubation. Mann-Whitney test indicate that MICs at 7 days incubation was not observed a significant difference between the effects of allicin and ketoconazole (p > 0.05), but MICs at 10 days incubation, a significant difference was observed (p < 0.05). On the other side, time kill studies revealed that allicin used its fungicidal activity within 12-24 h of management in vitro as well as ketoconazole. In conclusion, allicin showed very good potential as an antifungal compound against mycoses-causing dermatophytes, almost the same as the synthetic drug ketoconazole. Therefore, this antifungal agent appears to be effective, safe and suitable alternative for the treatment of dermatomycosis.

Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.

Aims: To compare the therapeutic effects of topical Artremisia sieberi 5% lotion with topical clotrimazole 1% lotion in the treatment of pityriasis versicolor. Materials and Methods: 100 patients with pityriasis versicolor and microscopic identification of Malassezia furfur were randomly assigned to treatment with either topical Artemisia sieberi 5% lotion (group 1) or topical clotrimazole 1% lotion (group 2) for 2 weeks. Group 1 and group 2 consisted of 51 and 49 patients respectively. The patients were evaluated both clinically and mycologically at baseline and every 2 weeks for a period of 4 weeks. Results: At the end of the second week, clinical cure rates were 86.3% and 65.3% for group 1 and group 2 respectively ( P