In vitro antifungal susceptibility of Cladophialophora carrionii, an agent of human chromoblastomycosis.

A global collection of Cladophialophora carrionii strains (n = 81) was tested against nine antifungal drugs. MIC90s of all strains were as follows in increasing order: itraconazole and posaconazole, 0.063 µg/ml; terbinafine, 0.125 µg/ml; isavuconazole and voriconazole, 0.25 µg/ml; caspofungin, 2 µg/ml; micafungin, 4 µg/ml; amphotericin B, 8 µg/ml; and fluconazole, 64 µg/ml.

Microdilution in vitro antifungal susceptibility of Exophiala dermatitidis, a systemic opportunist.

The in vitro activities of eight antifungal agents were determined against clinical (n = 63 genotype A, n = 3 genotype B) and environmental (n = 2 genotype A, n = 13 genotype B) strains of Exophiala dermatitidis. The resulting MIC(90)s for all strains (N = 81) were, in increasing order, as follows: posaconazole, 0.125 µg/ml; itraconazole, 0.25 µg/ml; voriconazole, 0.5 µg/ml; amphotericin B, 0.5 µg/ml; isavuconazole, 1 µ/ml; caspofungin, 8 µg/ml; anidulafungin, 8 µg/ml and fluconazole, 16 µg/ml. There were no significant differences in the patterns of susceptibility between genotypes A and B, environmental and clinical strains, isolates recovered from cutaneous and deep locations and strains from different geographical areas (P > 0.05). The difference in the MIC(90)s between each of these groups was not more than one dilution. The present study demonstrated that, based on in vitro activity, posaconazole and itraconazole have the highest activity against this fungus. In addition, voriconazole and the experimental broad-spectrum antifungal triazole, isavuconazole, both of which are available as intravenous preparations, have adequate activity against E. dermatitidis. However, in vivo efficacy remains to be determined.

Exophiala oligosperma involved in a refractory chronic rhinosinusitis.

Fungal rhinosinusitis refers to a wide variety of conditions caused by fungal infections of the paranasal sinuses. Allergic fungal rhinosinusitis and sinus fungus balls are mostly noted in healthy individuals. Aspergillus species are supposed to be the most common etiologic agents of the disorder, but melanized fungi also occur, and these potentially are able to lead to fatal dissemination into brain parenchyma. We report on a case of fungus ball in a 20-year-old female with refractory chronic rhinosinusitis (RCRS) and bronchial asthma due to the black yeast Exophiala oligosperma which was confirmed by mycological and molecular (sequences of ITS rDNA) investigations. Exophiala oligosperma has previously not been reported to cause fungus balls or invasive fungal rhinosinusitis. Patient underwent functional endoscopic sinusitis surgery and the hypertrophic mucosa was removed completely. Without antifungal therapy, successful cure was achieved after spray therapy with corticosteroids for 1 month, without any relapse after a 6 month-follow up.

Subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.

Pyrenochaeta romeroi is a rare agent of chronic, suppurative subcutaneous infections which ultimately lead to mycetoma. It has only rarely been reported from deep, non-mycetomatous infections. We describe a case of a subcutaneous phaeohyphomycotic cyst in a 45-year-old Indian female who suffered from verrucous plaque and a swelling (30 mm in diameter) on the right forearm that gradually increased in size over a period of 3 months. Direct microscopic examination with 10% KOH and histopathological investigation of exudates revealed septate hyphae without granules, the hallmark of mycetoma. The lesion appeared to be a subcutaneous phaeohyphomycotic cyst caused by P. romeroi. The suspected agent was recovered in culture, identified on the basis of morphologic features and its identification confirmed by sequencing of the internal transcribed spacer regions of rDNA. Treatment consisted of surgical excising of the cyst without any antifungal therapy. There was no relapse during a one-year follow-up and the patient was successfully cured. In vitro antifungal susceptibility tests demonstrated that itraconazole (0.5 microg/ml), isavuconazole (0.125 microg/ml) and posaconazole (0.5 microg/ml) had potent activity against this isolate of P. romeroi. High MICs were found with amphotericin B (4 microg/ml), fluconazole (>64 microg/ ml), voriconazole (4 microg/ml) and caspofungin (8 microg/ml). However, their clinical effectiveness in the treatment of P. romeroi infections remains to be evaluated.

The clinical spectrum of Exophiala jeanselmei, with a case report and in vitro antifungal susceptibility of the species.

Exophiala jeanselmei is clinically redefined as a rare agent of subcutaneous lesions of traumatic origin, eventually causing eumycetoma. Mycetoma is a localized, chronic, suppurative subcutaneous infection of tissue and contiguous bone after a traumatic inoculation of the causative organism. In advanced stages of the infection, one finds tumefaction, abscess formation and draining sinuses. The species has been described as being common in the environment, but molecular methods have only confirmed its occurrence in clinical samples. Current diagnostics of E. jeanselmei is based on sequence data of the Internal Transcribed Spacer (ITS) region of ribosomal DNA (rDNA), which sufficiently reflects the taxonomy of this group. The first purpose of this study was the re-identification of all clinical (n=11) and environmental strains (n=6) maintained under the name E. jeanselmei, and to establish clinical preference of the species in its restricted sense. Given the high incidence of eumycetoma in endemic areas, the second goal of this investigation was the evaluation of in vitro susceptibility of E.jeanselmei to eight conventional and new generations of antifungal drugs to improve antifungal therapy in patients. As an example, we describe a case of black grain mycetoma in a 43-year-old Thai male with several draining sinuses involving the left foot. The disease required extensive surgical excision coupled with intense antifungal chemotherapy to achieve cure. In vitro studies demonstrated that posaconazole and itraconazole had the highest antifungal activity against E. jeanselmei and E. oligosperma for which high MICs were found for caspofungin. However, their clinical effectiveness in the treatment of Exophiala infections remains to be determined.

Successful treatment of chromoblastomycosis of 36 years duration caused by Fonsecaea monophora.

We report a case of chromoblastomycosis in a 67-year-old female farmer, which involved a large (20 x 30 cm) cicatricial erythematous plaque on the inner side of her right thigh. The lesion was initially a small nodule which gradually extended over 36 years. Direct microscopic examination revealed a granulomatous lesion with muriform cells surrounded by giant cells. The mould recovered in cultures was dark olivaceous and identified as Fonsecaea monophora by ribosomal internal transcribe spacer (ITS) sequence data. The lesion was successfully cured after 4 months treatment with itraconazole, but there was a relapse.

Rhinocladiella aquaspersa, proven agent of verrucous skin infection and a novel type of chromoblastomycosis.

We report a case of chromoblastomycosis which resembled sporotrichosis due to the presence of warty nodules and lymphatic distribution on the forearm in a 56-year-old male. Mycological and histopathological investigation of exudates and biopsy tissue samples revealed a granulomatous lesion with muriform cells, the hallmark of chromoblastomycosis. The infection showed only localized expansion with verrucous plaques suggesting a new clinical type of the disease. The causative agent was identified as Rhinocladiella aquaspersa. This case prompted a study of the clinical spectrum of R. aquaspersa, through which we identified a second case caused by this fungus in a 62-year-old Brazilian female. The case was unusual in that R. aquaspersa exhibited hyphae rather than muriform cells in tissue. Given the difficulties treating chromoblastomycosis and other infections caused by melanized fungi, we evaluated the in vitro activities of extended-spectrum triazoles, amphotericin B, and echinocandins against these clinical isolates of R. aquaspersa. Itraconazole (MIC; 0.063 mg/l) and posaconazole (MIC; 0.125 mg/l) had the highest in vitro activities, while voriconazole and isavuconazole had somewhat lower activities (MICs; 2 mg/l) against the isolates. Amphotericin B and anidulafungin each had an MIC of 1 mg/l, whereas the MIC of caspofungin was 8 mg/l.

Potent in vitro activity of curcumin and quercetin co-encapsulated in nanovesicles without hyaluronan against Aspergillus and Candida isolates.

The rapid emergence of resistance to classical antifungals has increased the interest in novel antifungal compounds. Curcumin and quercetin are two natural plant-derived bioactive molecules shown to promote wound healing in injured tissues. In this study, we investigated the in vitro susceptibility of several Aspergillus and Candida isolates to curcumin and quercetin encapsulated in nanovesicles with and without hyaluronan and elucidated the efficacy of these nanovesicles as topical drug delivery systems. Antifungal susceptibility testing performed according to the CLSI guidelines indicated that curcumin-quercetin co-encapsulated in nanovesicles without hyaluronan (CUR-QUE-NV-WH) had stronger activity against Candida isolates than fluconazole. Furthermore, CUR-QUE-NV-WH showed efficacy against fluconazole-resistant Candida isolates as evidenced by MICs at least two times lower than those of fluconazole. Examination of skin permeation profiles using an in vitro Franz diffusion cell system revealed that curcumin and quercetin delivered by nanovesicles were released and accumulated in the skin; however, only quercetin could penetrate through the skin layers. Collectively, our results demonstrate that CUR-QUE-NV-WH has potent antifungal activity against Candida isolates and might be a topical treatment, which warrants its further investigation as a novel antifungal agent.

Candida africana vulvovaginitis: Prevalence and geographical distribution.

Candida africana has been recovered principally as a causative agent of vulvovaginal candidiasis (VVC) from different countries, which is likely to be misidentified as the typical Candida albicans or Candida dubliniensis. The current study aimed to characterize C. albicans species complex obtained from VVC based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed based on CLSI documents. Additionally, due to low knowledge concerning C. africana infections, we reviewed all published papers from 1991 to 2019. One hundred forty-four out of 287 patients were identified with Candida infection, among whom 151 isolates of Candida were obtained. Candida albicans 109 (72.1%), Candida glabrata 21 (13.9%), Candida krusei 8 (5.2%), Candida tropicalis 5 (3.3%), Candida africana 3 (1.9%), Candida parapsilosis 3 (1.9%) and C. dubliniensis 2 (1.3%) were isolated from patients. MIC results showed that C. africana isolates were susceptible to all tested antifungal drugs. Candida africana infections were more prevalent in Africa. One hundred fifteen (40.6%) of patients with C. africana candidiasis were from seven African countries, and Madagascar and Angola had the majority of cases. The epidemiological data, phenotypic, clinical features, ecologic similarity, and antifungal susceptibility profiles for better understanding of the pathogenic mechanisms and optimal treatment underlying non-CandidaalbicansCandida vulvovaginitis are highly recommended.

Comparison of in vitro antifungal activity of novel triazoles with available antifungal agents against dermatophyte species caused tinea pedis.

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=0.0005-0.004µg/mL), while fluconazole (MIC range=0.4-64µg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008µg/mL), followed by lanoconazole (0.003µg/mL), terbinafine (0.019µg/mL), itraconazole (0.085 µg/mL), ketoconazole (0.089µg/mL), econazole (0.097µg/mL), griseofulvin (0.351 µg/mL), voriconazole (0.583µg/mL) and fluconazole (11.58µg/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.

Comparative in vitro activities of seven antifungal drugs against clinical isolates of Candida parapsilosis complex.

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.

An unusual case of gastrointestinal basidiobolomycosis mimicking colon cancer; literature and review.

Gastrointestinal basidiobolomycosis (GIB), a rare fungal infection associated with high mortality, has been reported worldwide mainly from tropical and subtropical regions of Asia, USA, and Latin America. The clinical manifestations are highly diverse and non-specific depending on the underlying disease, but fever, abdominal pain, weight loss, diarrhea, constipation and chills have been observed. There are no prominent risk factors for GIB but climatic conditions and life style are related to this infection in arid and semi-arid regions. Therefore timely diagnosis and early treatment is a challenge. Herein, we present an unusual case of gastrointestinal basidiobolomycosis in a 54-year-old male, initially misdiagnosed as colon cancer. After follow-up, no evidence of relapse and the patient was successfully cured by liposomal amphotericin B. In addition, the differential diagnosis and histopathological findings are discussed with a review of the literature.

Tinea nigra by Hortaea werneckii, a report of 22 cases from Mexico.

Tinea nigra is a superficial mycosis caused by Hortaea werneckii. It is an infrequent asymptomatic infection that affects human palms and soles, and is mostly observed in tropical countries. We evaluate retrospectively twenty-two confirmed cases of tinea nigra from a total of eleven yr (1997-2007) and discuss the epidemiology, clinical features and treatment of this disease. In twelve cases, adults were involved, in 10, children. In nineteen cases the disorder was located on palms of hands and in three on soles of feet. In all cases, the obtained isolates were morphologically identified as Hortaea werneckii and the identification of ten isolates was retrospectively confirmed with the help of sequences of the internal transcribed spacer regions of the ribosomal DNA. The patients received topical treatment with Whitfield ointment, ketoconazole, bifonazole, or terbinafine. Treatment with keratolytic agents and topical antifungals was effective.

Biodiversity of the genus Cladophialophora.

Cladophialophora is a genus of black yeast-like fungi comprising a number of clinically highly significant species in addition to environmental taxa. The genus has previously been characterized by branched chains of ellipsoidal to fusiform conidia. However, this character was shown to have evolved several times independently in the order Chaetothyriales. On the basis of a multigene phylogeny (nucLSU, nucSSU, RPB1), most of the species of Cladophialophora (including its generic type C. carrionii) belong to a monophyletic group comprising two main clades (carrionii- and bantiana-clades). The genus includes species causing chromoblastomycosis and other skin infections, as well as disseminated and cerebral infections, often in immunocompetent individuals. In the present study, multilocus phylogenetic analyses were combined to a morphological study to characterize phenetically similar Cladophialophora strains. Sequences of the ITS region, partial Translation Elongation Factor 1-alpha and beta-Tubulin genes were analysed for a set of 48 strains. Four novel species were discovered, originating from soft drinks, alkylbenzene-polluted soil, and infected patients. Membership of the both carrionii and bantiana clades might be indicative of potential virulence to humans.

Evaluation of PCR-reverse line blot hybridization assay for simultaneous identification of medically important saprophytic fungi.

BACKGROUND: In immunocompromised patients suffering from invasive fungal infections, rapid identification of fungal species is important since the appropriate treatment is usually related to the responsible species. We describe here, an assay based on combination of PCR and reverse line blot hybridization (PCR/RLB) for differentiation causative agent of fungal infections. MATERIALS AND METHODS: We performed PCR/RLB assay on 10 reference strains, which include Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, and A. clavatus), Mucor circnelloides, Rhizopus oryzae, Alternaria alternata, Cladosporium herbarum, and Fusarium solani. Besides, twenty-two clinical specimens from patients with proven fungal infections were analyzed for the identification of species. The obtained results were then compared with the results of culture and sequence analysis. RESULTS: The fungal species-specific oligonucleotide probes were able to distinguish between all species represented in this study with the exception of cross-reactivity between A. niger and A. fumigatus species. Two specimens, which were represented as mixed fungi in culture, were identified properly by this method. Results of the RLB assay were concordant with the culture and ITS sequencing results. CONCLUSION: Our result demonstrate that the RLB assay potentially is suitable for rapid and simultaneous identification of variety fungal pathogens directly from culture as well as from clinical specimens.

Pesticide behavior in paddy fields and development of azole-resistant Aspergillus fumigatus: Should we be concerned?

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

Molecular epidemiology of environmental Cryptococcus species isolates based on amplified fragment length polymorphism.

OBJECTIVE: Cryptococcosis is a major opportunistic fungal infection caused by members of the genus Cryptococcus, mainly those belonging to the Cryptococcus neoformans/Cryptococcus gattii species complexes. Here, we report a comprehensive molecular epidemiological study of the environmental distribution of Cryptococcus isolates in Shiraz, Iran with review of litreature. METHOD: A total of 406 samples were obtained from Eucalyptus trees and 139 samples from pigeon droppings. Cryptococcus species identification and genotyping were performed by amplified fragment length polymorphism (AFLP) fingerprinting sequencing and sequencing of the ITS rDNA region. RESULTS: Majority of the isolates belonged to the Naganishia taxon (n=69) including N. albida (formerly C. albidus, n=62), N. globosa (formerly C. saitoi, n=4), N. adeliensis (formerly C. adeliensis, n=2), N. diffluens (formerly C. diffluens, n=1), and the identified C. neoformans isolates (n=25) belonged to genotype AFLP1/VNI (n=22) and AFLP1B/VNII (n=3). CONCLUSION: More research efforts should be employed to isolate C. gattii species complex from environmental niches in Iran and provide additional evidence related to novel molecular types.

Molecular analysis and pathogenicity of the Cladophialophora carrionii complex, with the description of a novel species.

Cladophialophora carrionii is one of the four major etiologic agents of human chromoblastomycosis in semi-arid climates. This species was studied using sequence data of the internal transcribed spacer region of rDNA, the partial beta-tubulin gene and an intron in the translation elongation factor 1-alpha gene, in addition to morphology. With all genes a clear bipartition was observed, which corresponded with minute differences in conidiophore morphology. A new species, C. yegresii, was introduced, which appeared to be, in contrast to C. carrionii, associated with living cactus plants. All strains from humans, and a few isolates from dead cactus debris, belonged to C. carrionii, for which a lectotype was designated. Artificial inoculation of cactus plants grown from seeds in the greenhouse showed that both fungi are able to persist in cactus tissue. When reaching the spines they produce cells that morphologically resemble the muriform cells known as the "invasive form" in chromoblastomycosis. The tested clinical strain of C. carrionii proved to be more virulent in cactus than the environmental strain of C. yegresii that originated from the same species of cactus, Stenocereus griseus. The muriform cell expressed in cactus spines can be regarded as the extremotolerant survival phase, and is likely to play an essential role in the natural life cycle of these organisms.

Epidemiological and mycological characteristics of candidemia in Iran: A systematic review and meta-analysis.

To date, there has been no comprehensive review of the epidemiology, risk factors, species distribution, and outcomes of candidemia in Iran. This study aimed to perform a systematic review and meta-analysis of all reported candidemia cases in Iran until December 2015. The review process occurred in three steps, namely a literature search, data extraction and statistical analyses. After a comprehensive literature search, we identified 55 cases. The mean age of patients was 46.80±24.30 years (range 1-81 years). The main risk factors for candidemia were surgery and burns (23.6%), followed by malignancies (20%), use of broad-spectrum antibiotics (18.2%), and diabetes (7.3%). Candida parapsilosis (n=17, 30.8%) was the leading agent, followed by Candida albicans (n=15, 27.3%), Candida glabrata (n=10, 18.2%), and Candida tropicalis (n=8, 14.5%). The frequencies of candidemia cases due to C. glabrata, C. parapsilosis, and C. albicans were significantly higher among patients aged>60, 21-40, and 41-60 years, respectively. Comparison of risk factors for candidemia by multiple logistic regression showed that one of the most important risk factors was surgery (OR: 4.245; 95% CI: 1.141-15.789; P=0.031). The outcome was recorded in only 19 cases and 13 of those patients (68.4%) expired. This study confirms that knowledge of the local epidemiology is important when conducting surveillance studies to prevent and control candidemia and will be of interest for antifungal stewardship.

Consistent high prevalence of Exophiala dermatitidis, a neurotropic opportunist, on railway sleepers.

Environmental isolation of black yeasts potentially causing human disorders is essential for understanding ecology and routes of infection. Several Exophiala species show prevalence for man-made environments rich in monoaromatic compounds, such as creosote-treated or petroleum-stained railway sleepers. Ambient climatic conditions play a role in species composition in suitable habitats. Therefore, the aim of the present study was to establish the composition of Exophiala species in railway stations as a potential source of human infections in a subtropical region with evaluation of their antifungal susceptibility profiles. We examined 150 railway samples using cotton swabs moistened with sterile physiological saline. Black yeasts and relatives were selected on theirs colony morphology and identified based on ITS rDNA sequencing. Overall, 36 (24%) of samples were positive for black yeast-like fungi, i.e., Exophiala dermatitidis (n=20, 55.6%) was predominant, followed by E. phaeomuriformis (n=9, 25%), E. heteromorpha (n=5, 13.9%), and E. xenobiotica (n=2, 5.6%). Massive contaminations of E. dermatitidis were seen on railway sleepers on creosoted oak wood at the region close to the sea level, while in cold climates were primarily contaminated with clinically insignificant or rare human opportunists (E. crusticola). It seems that, high temperature and humidity are significant effect on species diversity. Moreover, the MIC results for all E. dermatitidis and E. phaeomuriformis strains revealed the widest range and the highest MICs to caspofungin (range 1-16mg/L, Geometric mean 4.912mg/L), and the lowest MIC for posaconazole (0.016-0.031mg/L, G mean 0.061mg/L). However, their clinical effectiveness in the treatment of Exophiala infections remains to be determined.