Publications by authors named "Mahdi Abastabar"

49 Publications

Diversity of Geophilic Dermatophytes Species in the Soils of Iran; The Significant Preponderance of .

J Fungi (Basel) 2021 Apr 28;7(5). Epub 2021 Apr 28.

Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 61357-15794, Iran.

A molecular epidemiology study was conducted between 2016 and 2017 by a network of collaborators from 12 provinces in the Islamic Republic of Iran. A total of 1484 soil samples from different habitats were screened for the presence of dermatophytes by using the hair baiting technique. The primary identification of isolates was carried out by amplification and I restriction fragment length polymorphism (RFLP) of the internal transcribed spacers regions of ribosomal DNA (ITS-rDNA). The identifications, especially in the cases of isolates with unknown RFLP patterns, were confirmed by sequencing of the ITS-rDNA region. As a result, 256 isolates were recovered. The isolation rate was higher in soils with pH range 7.1-8.0, collected from animal habitats ( = 78; 34%) and parks and gardens ( = 75; 32%), geographically from Mazandaran Province ( = 115; 49.5%) and seasonally in the spring ( = 129; 50.4%), all of which were statistically significant ( < 0.05). The dermatophytes comprising five species of the two genera, viz., ( = 214), ( = 34), ( = 5), ( = 2) and ( = 1), were isolated. The geophilic dermatophytes occurred in various soils from different parts of Iran; however, surprisingly, emerged as the dominant species, outnumbering the common geophilic species of . For the definitive identification of soil inhabitant dermatophytes, DNA-based identification is strongly recommended.
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http://dx.doi.org/10.3390/jof7050345DOI Listing
April 2021

Molecular Identification and Antifungal Susceptibility of Yeasts and Molds Isolated from Patients with Otomycosis.

Mycopathologia 2021 Mar 15. Epub 2021 Mar 15.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

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.
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http://dx.doi.org/10.1007/s11046-021-00537-1DOI Listing
March 2021

In vitro activities of antifungal drugs against a large collection of Trichophyton tonsurans isolated from wrestlers.

Mycoses 2020 Dec 13;63(12):1321-1330. Epub 2020 Sep 13.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

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.
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http://dx.doi.org/10.1111/myc.13172DOI Listing
December 2020

Phylogenetic Analysis of Clinically Relevant Fusarium Species in Iran.

Mycopathologia 2020 Jun 6;185(3):515-525. Epub 2020 Jun 6.

Center of Expertise in Mycology of Radboud University Medical Center, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Fungi of the genus Fusarium are well known as major plant pathogens but also cause a broad spectrum of human infections. Sixty-three clinical isolates, collected during 2014-2017, were identified using a part of the TEF1 gene as barcoding marker. Fusarium fujikuroi species complex (FFSC, n = 41, 65%) showed to be the dominant etiological agent, followed by F. solani species complex (FSSC, n = 14, 22%) and F. oxysporum species complex (FOSC, n = 7, 11%). There was one strain belonging to F. lateritium species complex (FLSC, n = 1, 1.5%). For final identification, a phylogenetic tree was constructed including the type strains of each species complex. Most cases of fusariosis were due to nail infection (n = 38, 60.3%), followed by keratitis (n = 22, 34%). Fusarium infections are difficult to be treated due to their intrinsic resistance to different azoles; however, accurate and fast identification of etiological agents may enhance management of the infection. We present the first phylogenetic study on clinical Fusarium spp. from Iran.
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http://dx.doi.org/10.1007/s11046-020-00460-xDOI Listing
June 2020

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

Mycoses 2020 Jul 24;63(7):755-761. Epub 2020 May 24.

Invasive Fungi Research Center/Department of Medical mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Several previous studies have shown cavitary lung lesions in old pulmonary tuberculosis (PTB) increase the risk of fungus ball. Detection of galactomannan (GM) in bronchoalveolar lavage (BAL) is also proposed as a diagnostic approach for the fungus ball.

Objectives: We evaluated the diagnosis of fungus balls and GM levels in BAL samples in PTB patients.

Methods: A total of 110 PTB patients were evaluated for fungus ball during 2017-2019. The patients were evaluated for radiological, histopathological results and mycological findings of BAL including GM detection and culture. The sensitivity, specificity and positive and negative predictive value for GM test were calculated. The optimal cut-off for BAL GM testing was determined by receiver operating characteristic (ROC).

Results: Of 110 PTB patients, nine (8.18%) showed fungus ball, all with old PTB. The molecularly confirmed Aspergillus species were A. flavus, A. fumigatus and A. ochraceus. The sensitivity and specificity of BAL GM ≥ 0.5 in old PTB patients with fungus ball were 100%, 41.5%, respectively. The statistical analysis of the mean ± SEM of BAL GM levels was demonstrated a higher levels of GM in patients with fungus ball/aspergilloma compared to old PTB patients without fungus ball/aspergilloma. The optimal cut-off value for BAL GM was determined as 0.50 by ROC curve analysis.

Conclusion: According to our results, we can recommend the detection of GM in BAL samples as a diagnostic approach for fungus ball in PTB patients.
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http://dx.doi.org/10.1111/myc.13099DOI Listing
July 2020

Relationship between spirometry results and colonisation of Aspergillus species in allergic asthma.

Clin Respir J 2020 Mar 26. Epub 2020 Mar 26.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Introduction And Objectives: Exposure to fungi in patients with asthma leads to the release of various fungal antigens, which can increase the severity of asthma. Regarding this, the present study was conducted to evaluate the relationship between the colonisation of Aspergillus species and spirometry results in allergic asthma.

Materials And Methods: Two hundred sixteen patients with mild to severe asthma and 30 healthy controls were included. All participants underwent pulmonary function tests. Furthermore, sputum samples were collected from each subject. Each sputum sample was subjected to direct microscopic examination and fungal culture. All cultured Aspergillus colonies were identified at species level by molecular methods. Finally, all available data from sputum culture and spirometry test were analysed.

Results: Out of 216 sputum samples, 145 (67.1%) were positive for fungal growth. Furthermore, out of 264 grown fungal colonies, 137 (51.9%) were Aspergillus species. Among the Aspergillus isolates, A. flavus (29.2%) was the most prevalent species, followed by A. fumigatus (27.7%). The mean forced expiratory volume in one second (FEV1) in the mild, moderate and severe asthmatic patients with a positive sputum culture for fungi were obtained as 90.0 ± 11.1, 71.1 ± 15.9 and 54.9 ± 16.4, respectively. In general, Aspergillus species colonisation had no statistically significant effect on spirometry results of study patients.

Conclusion: Our results showed that there is no difference in the FEV1 and forced vital capacity between Aspergillus positive and negative patients in any asthma severity group.
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http://dx.doi.org/10.1111/crj.13192DOI Listing
March 2020

Emergence of Terbinafine Resistant in Iran, Harboring Mutations in the Squalene Epoxidase () Gene.

Infect Drug Resist 2020 13;13:845-850. Epub 2020 Mar 13.

Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Introduction: and are important causative agents of superficial mycoses, demonstrating emergent antifungal drug resistance. We studied the antifungal susceptibility profiles in Iranian isolates of these two species.

Methods: A total of 96 and 45 isolates were subjected to molecular typing by ribosomal ITS region. Antifungal susceptibility profiles for terbinafine, griseofulvin, clotrimazole, efinaconazole, luliconazole, amorolfine and ciclopirox were obtained by CLSI broth microdilution method. The squalene epoxidase () gene was subjected to sequencing for mutations, if any, in isolates exhibiting elevated MICs for terbinafine.

Results: Luliconazole and efinaconazole showed the lowest MIC values against and isolates. There were five isolates with terbinafine MICs ≥32 µg/mL in our sample. They belonged to type VIII and harbored two alternative gene sequence variants, leading to Phe397Leu and Ala448Thr or Leu393Ser and Ala448Thr substitutions in the enzyme. All terbinafine resistant strains could be inhibited by luliconazole and efinaconazole.

Conclusion: This study documented a step in the global spread of resistance mechanisms in . However, treatment alternatives for resistant isolates were available.
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http://dx.doi.org/10.2147/IDR.S246025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078656PMC
March 2020

Antifungal Activity of a Novel Triazole, Efinaconazole and Nine Comparators against 354 Molecularly Identified Aspergillus Isolates.

Mycopathologia 2020 Apr 28;185(2):357-365. Epub 2020 Feb 28.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Management of superficial aspergillosis is a major challenge owing to the frequent relapses and treatment failure, which may pose a potential risk, thereby gradually developing resistant species. Therefore, necessitating the development of new antifungals with higher potency should be considered as alternative strategies for efficient management of infections. We aimed to investigate the susceptibility of Aspergillus isolates toward a novel triazole, efinaconazole, in comparison with various classes of antifungal drugs. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. Efinaconazole exhibited poor activity against mutant A. fumigatus strains, A. niger sensu stricto, and A. tubingensis with GM MIC values of 3.62, 1.62, and 2 μg/ml, respectively; however, surprisingly, it efficiently inhibited the growth of A. terreus sensu stricto, followed by wild-type A. fumigatus and A. flavus with GM MIC values of 0.29, 0.42, and 0.52 μg/ml, respectively. Presumably, efinaconazole is inefficient in aspergillosis treatment due to the low susceptibility of A. niger sensu stricto, A. tubingensis, and mutant A. fumigatus; however, it may be effective in treating superficial aspergillosis caused by wild-type A. fumigatus, A. terreus sensu stricto, and A. flavus. Further studies are needed to determine how these findings may translate into in vivo efficacy.
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http://dx.doi.org/10.1007/s11046-020-00434-zDOI Listing
April 2020

Species distribution and susceptibility profiles of Candida species isolated from vulvovaginal candidiasis, emergence of C. lusitaniae.

Curr Med Mycol 2019 ;5(4):26-34

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: The aim of the current study was to investigate the epidemiology of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC), as well as the antifungal susceptibility patterns of species isolates.

Materials And Methods: A cross-sectional study was carried out on 260 women suspected of VVC from February 2017 to January 2018. In order to identify species isolated from the genital tracts, the isolates were subjected to polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using enzymes and sequencing. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guidelines (M27-A3).

Results: Out of 250 subjects, 75 (28.8%) patients were affected by VVC, out of whom 15 (20%) cases had RVVC. Among the species, was the most common species (42/95; 44.21%), followed by (18/95; 18.95%), (13/95; 13.69%), (8/95; 8.42%), (6/95; 6.31%), (5/95; 5.26%), (2/95; 2.11%), and (1/95; 1.05%), respectively. Multiple species were observed in 28% (21/75) of the patients. Nystatin showed the narrowest range of minimum inhibitory concentration (MIC) (0.25-16 μg/ml) against all strains, whereas fluconazole (0.063-64 μg/ml) demonstrated the widest MIC range. In the current study, as the second most common causative agent of VVC, was susceptible to all antifungal agents. Furthermore, 61.1% of isolates were inhibited at a concentration of ≤ 2 μg/ml while 38.9% (n=7) of them exhibited fluconazole MICs above the epidemiologic cutoff values (ECV). species showed the highest overall resistance against fluconazole (61.3%), followed by itraconazole (45.2%) and caspofungin (23.7%). All of strains were resistant to itraconazole with a MIC value of ≥ 1 μg/ml; in addition, 87.5% of them were resistant to fluconazole. Moreover, 100% and 87.5% of strains were resistant to caspofungin and fluconazole, respectively.

Conclusion: As the findings revealed, the majority of VVC cases were caused by non- species which were often more resistant to antifungal agents. generally had fluconazole MICs above the ECV. Given the propensity of to develop resistance under drug pressure, antifungals should be administered with caution. The emergence of these species justify the epidemiological surveillance surveys to watch out the distribution of yeast species.
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http://dx.doi.org/10.18502/cmm.5.4.2062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034787PMC
January 2019

Molecular epidemiology of Tinea gladiatorum in contact sports in northern Iran.

Mycoses 2020 May 13;63(5):509-516. Epub 2020 Mar 13.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Tinea gladiatorum as the major health concern among combat athletes and the most common cause of a decrease in the quality of their sports activities.

Objectives: This study aimed to determine the molecular epidemiology of tinea gladiatorum in contact sports in Mazandaran Province, Northern Iran.

Materials/methods: In total, 631 suspected athletes out of 4240 ones were screened for tinea gladiatorum in this cross-sectional study from May 2018 to February 2019. The infection was confirmed by direct microscopy and culture tests. The causative agents were identified by polymerase chain reaction-restriction fragment length polymorphism method on ITS rDNA region. The indoor environmental factors were evaluated in 81 sports halls in terms of temperature (°C), humidity (%), density (m /athletes) and the number of ventilators.

Results: Tinea gladiatorum was confirmed in 6.5% (278/4240) of the athletes. Tinea corporis was the most common type of tinea (192/278; 69.0%), and 175 cases (27.7%) had more than one type of tinea. Moreover, Trichophyton tonsurans (192/203; 94.5%) was the most aetiological agent in all athletes followed by Microsporum canis (6/203; 2.9%), Trichophyton rubrum (2/203; 0.9%) and Trichophyton interdigitale (1/203; 0.4%). There was no significant association between the prevalence of tinea gladiatorum and the indoor environmental factors.

Conclusion: T. tonsurans is the most common agent of tinea gladiatorum in Northern Iran. Since no positive culture of dermatophyte was obtained from mats, it seems that skin-to-skin contact would be the most probable mode of transmission among wrestlers. Accordingly, periodical checkups should be considered by health care providers.
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http://dx.doi.org/10.1111/myc.13069DOI Listing
May 2020

Indole-derived chalcones as anti-dermatophyte agents: In vitro evaluation and in silico study.

Comput Biol Chem 2020 Feb 23;84:107189. Epub 2019 Dec 23.

Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.compbiolchem.2019.107189DOI Listing
February 2020

A multi-centered study of colonization in patients with respiratory disorders: Is there a colonization trend in the elderly?

Curr Med Mycol 2019 Sep;5(3):19-25

Department of Molecular Pathology, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Purpose: colonization plays a key role in the progression of pulmonary infection. However, there are limited data regarding the colonization of these fungi in the patients residing in different regions of Iran. Regarding this, the present study was conducted to evaluate the prevalence of colonization in non-HIV-infected patients with respiratory failure introduced by physicians using nested polymerase chain reaction (PCR).

Materials And Methods: This study was conducted on 136 samples obtained from 136 patients with respiratory disorders referring to different hospitals in the capital and north of Iran during 2013-2015. The samples were collected using bronchoalveolar lavage (BAL; n=121) and sputum induction (n=15). Nested PCR method targeting mtLSU rRNA gene was used for the detection of DNA in the specimens.

Results: The nested PCR analysis resulted in the detection of DNA in 32 (23.5%) patients. The mean age of the participants was 49.04±11.94 years (age range: 14-90 years). The results revealed no correlation between colonization and gender. The studied patients were divided into two groups of immunocompromised and immunocompetent patients. In the regard, 25.4% of the patients with detectable DNA were immunocompromised and had cancer, organ transplantation, asthma, sarcoidosis, dermatomyositis, chronic obstructive pulmonary disease, bronchiectasis, and pulmonary vasculitis. On the other hand, DNA was detected in 21.8% of the immunocompetent patients. Frequencies of DNA detection in the patients with tuberculosis, hydatid cyst, and unknown underlying diseases were obtained as 20.8%, 25%, and 22%, respectively. The prevalence of colonization varied based on age. In this regard, colonization was more prevalent in patients aged above 70 years.

Conclusion: As the findings indicated, non-HIV-infected patients, especially the elderly, had a high prevalence of colonization. Therefore, these patients are probably a potential source of infection for others. Regarding this, it is of paramount importance to adopt monitoring and prophylactic measures to reduce this infection.
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http://dx.doi.org/10.18502/cmm.5.3.1742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910707PMC
September 2019

Molecular epidemiology and antifungal susceptibility profiles of clinical species complex.

J Med Microbiol 2020 Jan;69(1):72-81

Center of Expertise in Microbiology, Infection Biology, and Antimicrobial Pharmacology, Tehran, Iran.

Limited data regarding the epidemiology and susceptibility profiles of cryptococcosis are available in the Middle East. Our study aimed to evaluate the molecular diversity, mating types and antifungal susceptibility pattern of species (=14) isolated from 320 suspected patients with cryptococcosis. The gene was subjected to restriction fragment length polymorphism and sequence analysis. In addition, antifungal susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) M27-A4 and M59 guidelines. Overall, 14 (4.4 %) patients were confirmed as cryptococcosis. Based on molecular type, 85.7 and 14.3 % of the isolates were VN I and VN II, respectively. Phylogenetic analysis of 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) and highest (8 µg ml) MICs. The epidemiological cutoff values (ECVs) for amphotericin B, fluconazole, voriconazole and 5-fluorocytosine encompassed ≥97 % of all 14 . 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. Our findings may significantly contribute to the development of management strategies for patients at a higher risk of cryptococcosis, particularly HIV-positive individuals.
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http://dx.doi.org/10.1099/jmm.0.001101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137767PMC
January 2020

Genetic diversity and antifungal susceptibility patterns of Aspergillus nidulans complex obtained from clinical and environmental sources.

Mycoses 2020 Jan 3;63(1):78-88. Epub 2019 Nov 3.

Medical Mycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

The molecular epidemiology and antifungal susceptibility of Aspergillus nidulans species complex has not been well studied. To evaluate the genetic diversity and antifungal susceptibility patterns of clinical and environmental isolates of A. nidulans complex. Sixty clinical and environmental isolates of Aspergillus section Nidulantes were collected from five countries (Iran, The Netherlands, Spain, Portugal and Greece). The species were molecularly identified by sequencing of β-tubulin gene. The genetic diversity of A nidulans complex isolates (n = 54) was determined with a microsatellite genotyping assay. Antifungal susceptibility profile was determined using EUCAST method. The isolates were classified as A nidulans (46.7%), A spinulosporus (26.6%), A quadrilineatus (10%), A pachycristatus (3.3%), A rugulosus (3.3%), A unguis (5%), A creber, (1.7%), A olivicola (1.7%) and A sydowii (1.7%). Thirty-four sequence types (STs) were identified among the 54 A nidulans complex isolates. A high level of genetic diversity was found among A nidulans sensu stricto strains but low diversity was found among A spinulosporus strains. Amphotericin B showed high MICs to all species. The most active azole was posaconazole (GM = 0.64 mg/L), while itraconazole showed the highest MICs among azoles (GM = 2.95 mg/L). A spinulosporus showed higher MICs than A nidulans sensu stricto for all antifungals except for micafungin and anidulafungin. Interspecies variations may result in differences in antifungal susceptibility patterns and challenge antifungal therapy in infections caused by A nidulans. Differences in the distribution of STs or persistence of multiple STs might be related to the sources of isolation and niche specialisation.
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http://dx.doi.org/10.1111/myc.13019DOI Listing
January 2020

Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry.

Mycoses 2019 Dec 15;62(12):1182-1188. Epub 2019 Oct 15.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Aspergillus flavus is a major cause of severe non-invasive fungal infections in the Middle Eastern countries. However, it is difficult to distinguish A flavus from A oryzae.

Objectives: To assess the potential of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in discriminating between A flavus and A oryzae and compare it with β-tubulin gene sequencing.

Methods: We used the Bruker Daltonik MALDI-TOF MS system to analyse 200 clinical and environmental A flavus isolates and one A pseudonomius and one A alliaceus (Aspergillus section Flavi) isolate a priori identified as such by sequencing of the β-tubulin gene.

Results: All 200 A flavus isolates were identified at the genus level and 176 (88%) at the species levels by MALDI-TOF MS based on the spectral log-scores (≥2.0 and 1.7-1.99, respectively); among them, only 18 (10.2%) were confirmed as A flavus, whereas 35 (19.9%) were identified as A oryzae and 123 (69.9%) as A flavus/A oryzae. Aspergillus pseudonomius and A alliaceus were misidentified as A flavus and A parasiticus with log-score values of 1.39 and 1.09, respectively.

Conclusions: The results indicate that the commercially available Bruker Daltonik MALDI-TOF MS score database cannot separate A flavus and A oryzae species. We also showed that establishment of an in-house library is a useful tool to discriminate closely related Aspergillus species, including A flavus and A oryzae.
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http://dx.doi.org/10.1111/myc.13010DOI Listing
December 2019

Trichophyton mentagrophytes and T interdigitale genotypes are associated with particular geographic areas and clinical manifestations.

Mycoses 2019 Nov 9;62(11):1084-1091. Epub 2019 Sep 9.

Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

The fungi Trichophyton mentagrophytes and T interdigitale account for significant amount of dermatophytosis cases worldwide. These two dermatophytes form a species complex and have a number of ribosomal internal transcribed spacer (ITS) region genotypes, allowing simultaneous species identification and strain typing. Our aim was to describe the geographic distribution of T mentagrophytes/T interdigitale ITS region genotypes and find an association between the genotypes and clinical presentations of respective infections. We performed rDNA ITS region sequencing in 397 Iranian T mentagrophytes/T interdigitale isolates and analysed all available in GenBank entries with sequences of this kind. For the study, 515 clinical annotations were available. Statistical analysis was performed by chi-squared test and Spearman rank correlation analysis. A total of 971 sequences belonged to genotypes with at least 10 geographic annotations and were classified on the basis of exclusive occurrence in a particular region or high relative contribution to a regional sample. We discerned Asian and Oceanian ("KU496915" Type V, "KT192500" Type VIII, "KU315316"), European ("FM986750" Type III, "MF926358" Type III*, "KT285210" Type VI) and cosmopolitan ("FM986691" Type I, "JX122216" Type II, "KP132819" Type II* and "AF170453" Type XXIV) genotypes. There was statistically significant difference in the ITS genotype distribution between different affected body sites. Trichophyton mentagrophytes "KT192500" Type VIII correlated with tinea cruris, T mentagrophytes "KU496915" Type V correlated with tinea corporis, T interdigitale "JX122216" Type II correlated with tinea pedis and onychomycosis. Trichophyton mentagrophytes and T interdigitale genotypes can be associated with distinct geographic locations and particular clinical presentations.
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http://dx.doi.org/10.1111/myc.12993DOI Listing
November 2019

In vitro activities of 15 antifungal drugs against a large collection of clinical isolates of Microsporum canis.

Mycoses 2019 Nov 1;62(11):1069-1078. Epub 2019 Oct 1.

Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences.

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.
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http://dx.doi.org/10.1111/myc.12986DOI Listing
November 2019

Identification of clinical dermatophyte isolates obtained from Iran by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Curr Med Mycol 2019 Jun;5(2):22-26

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used to discriminate among pathogenic microorganisms in clinical laboratories. The aim of this study was to assess the utility of MALDI-TOF MS in the routine identification of clinical dermatophyte isolates obtained from various geographical regions of Iran.

Materials And Methods: A total of 94 isolates, including (n=44), (n=40), (n=4), (n=4), and (=1), were analyzed in this study. The identity of each isolate was determined by polymerase chani reaction amplification and sequencing of the internal transcribed spacer (ITS) region of nuclear-encoded ribosomal DNA and also MALDI-TOF MS. The obtained data by molecular approach were compared with MALDI-TOF MS.

Results: The MALDI-TOF MS led to the identification of 44 (47%) isolates at the species level by generating the spectral score values of ≥ 2.0. However, there was not sufficient agreement between the results of the molecular-based ITS identification methods and MALDI-TOF MS in the species identification of 16 (17%) isolates. The Bruker Daltonics database was also not able to identify protein spectra related to 12 isolates (13%), including . (n=5), . (n=4), . (n=2), and . (n=1).

Conclusion: According to the results, the utility of MALDI-TOF MS as a routine diagnostic tool for the accurate and reliable identification of dermatophytes can be justified whenever the protein spectra of a large set of worldwide clinical isolates are included in the commercial libraries. In addition, MALDI-TOF MS can be alternatively used to construct an in-house reference database.
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http://dx.doi.org/10.18502/cmm.5.2.1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626716PMC
June 2019

Potential Fifth Clade of Candida auris, Iran, 2018.

Emerg Infect Dis 2019 09 17;25(9):1780-1781. Epub 2019 Sep 17.

Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.
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http://dx.doi.org/10.3201/eid2509.190686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711235PMC
September 2019

Niosome-loaded antifungal drugs as an effective nanocarrier system: A mini review.

Curr Med Mycol 2018 Dec;4(4):31-36

The Health of Plant and Livestock Products Research Center, Department of Medical Nanotechnology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Skin is an important organ of the body due to offering an accessible and convenient site for drug administration. One of the disadvantages of transdermal drug delivery is the low penetration rate of drugs through the skin. Over the past decades, nanoparticles have been used as drug delivery systems to increase therapeutic effects or reduce toxicity. Encapsulation of drugs in nanoparticulate vesicles simplifies the transports of drugs into and across the skin. Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). In recent years, there has been much research on the use of niosomal systems for the delivery of fungal drugs. A review of the literature investigating the advantages of niosomes in antifungal drug delivery can elucidate the efficiency and superiority of this nanocarrier over other nanocarriers.
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http://dx.doi.org/10.18502/cmm.4.4.384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386503PMC
December 2018

Prevalence of specific immunoglobulin E and G against in patients with asthma.

Curr Med Mycol 2018 Dec;4(4):7-11

Invasive Fungi Research Centre, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: as a ubiquitous fungus can be found in the respiratory tract of the asthmatic and healthy people. The inhalation of spores leads to an immune response in individuals with asthma and results in the aggravation of the clinical symptoms. The present study aimed to investigate the prevalence of specific immunoglobulin E and G IgE and IgG) against in asthmatic patients.

Materials And Methods: This study was conducted on 200 consecutive patients with moderate to severe asthma referring to Masih Daneshvari hospital Tehran, Iran, from January 2016 to February 2018. Skin prick test (SPT) was performed in all subjects with allergens. Moreover, all patients underwent specific IgE testing for using Hycor method. Enzyme immune assay was applied to measure total IgE and specific IgG.

Results: According to the results, the mean age of the patients was 45.8 years (age range: 18-78 years). The mean levels of total IgE and specific IgE in asthmatic patients were obtained as 316.3 (range: 6-1300 IU/ml) and 1.5 (range: 0.1-61.3 IU/ml), respectively. Out of 200 patients, 27 (13.5%), 65 (32.5%), 22 (11.0%), and 86 (43.0%) cases had positive SPT, total IgE of > 417 IU/ml, specific IgE, and IgG, respectively. The level of these variables in patients with severe asthma were 16 (16.5%), 36 (37.1%), 15 (15.5%), and 46 (47.4%), respectively.

Conclusion: As the findings indicated, reactivity to is a remarkable phenomenon in asthmatic patients. It is also emphasised that the climatic condition may affect the positive rate of hypersensitivity to .
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http://dx.doi.org/10.18502/cmm.4.4.380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386509PMC
December 2018

Fungal epidemiology in cystic fibrosis patients with a special focus on Scedosporium species complex.

Microb Pathog 2019 Apr 8;129:168-175. Epub 2019 Feb 8.

Center of Expertise in Microbiology, Infection Biology and Antimicrobial Pharmacology, Tehran, Iran.

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.
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http://dx.doi.org/10.1016/j.micpath.2019.02.009DOI Listing
April 2019

Novel Point Mutations in and Genes Associated with Itraconazole and Posaconazole Resistance in Isolates.

Microb Drug Resist 2019 Jun 18;25(5):652-662. Epub 2019 Jan 18.

1 Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

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 ( and ) 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 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.
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http://dx.doi.org/10.1089/mdr.2018.0300DOI Listing
June 2019

Prosthetic valve endocarditis caused by multidrug-resistant in a patient with myelodysplasia syndrome: A case report and literature review.

Curr Med Mycol 2018 Sep;4(3):23-27

Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: endocarditis is an infrequent disease with a high mortality rate, which commonly occurs in immunosuppressed patients with cardiac valve replacement. We reported a 70-year-old woman diagnosed with prosthetic valve endocarditis (PVE). This study also involved a review of all published cases of PVE from 1970.

Case Report: Herein, we reported a 70-year-old woman with the history of severe mitral stenosis and myelodysplasia syndrome. She underwent mitral valve replacement for two times. The blood cultures were positive, and phenotypic identification of the isolates at the species level was performed based on microscopic and macroscopic characteristics. In the second prosthetic valve replacement, huge fungal white and creamy vegetation was observed which was identified as based on the conventional and molecular methods. Despite the administration of antifungal treatments, the patient passed away probably due to the multidrug-resistant PVE.

Conclusion: As PVE is a late consequence of prosthetic valve replacement, extended follow-up visits, early diagnosis, repeating valve replacement surgeries, and timely selective antifungal treatments are warranted.
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http://dx.doi.org/10.18502/cmm.4.3.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315203PMC
September 2018

Candida auris otomycosis in Iran and review of recent literature.

Mycoses 2019 Feb;62(2):101-105

Department of Medical Mycology/Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Candida auris is a multidrug-resistant yeast emerging in immunocompromised and in otherwise healthy individuals. Due to difficulties in microbiological identification of C. auris because of the lack of available laboratory technology in developing countries, the number of patients affected is most likely underestimated. We report the first case of C. auris otitis which now adds Iran as the fifth country around the Persian Gulf, in addition to Kuwait, Oman, United Arab Emirates and Saudi Arabia. Candida auris is an unknown pathogen in routine laboratories in Iran because most Candida isolates are probably misdiagnosed. Otomycosis seems to be a different clinical presentation of C. auris mainly involving isolates from the East-Asian clade. We compared the mycological and clinical details of the Iranian patient with other cases of otitis reported since the last review of C. auris otomycosis in 2017.
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http://dx.doi.org/10.1111/myc.12886DOI Listing
February 2019

In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis.

J Infect Chemother 2019 Feb 18;25(2):157-160. Epub 2018 Sep 18.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Middle East Center of Excellence for Infection Biology and Antimicrobial Pharmacology, Tehran, Iran; Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1016/j.jiac.2018.07.018DOI Listing
February 2019

Low Antifungal Activity of Tavaborole against Yeasts and Molds from Onychomycosis.

Antimicrob Agents Chemother 2018 12 26;62(12). Epub 2018 Nov 26.

Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

The 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 species, species, and dermatophytes.
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http://dx.doi.org/10.1128/AAC.01632-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256807PMC
December 2018

Promising antileishmanial activity of novel imidazole antifungal drug luliconazole against Leishmania major: In vitro and in silico studies.

J Glob Antimicrob Resist 2018 09 21;14:260-265. Epub 2018 May 21.

Pharmaceutical Sciences Research Center, Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Objectives: Pentavalent antimonials have been used for the treatment of leishmaniasis for over 70 years, however they are limited by their toxicity. Unfortunately, the efficacy of first-line drugs for the treatment of leishmaniasis has decreased and resistance is noticeable. Luliconazole is a new azole with unique effects on fungi that has not yet been tested on Leishmania parasites.

Methods: In this study, the cytotoxicity and antileishmanial activity of luliconazole were evaluated in vitro against promastigotes and intracellular amastigotes of Leishmania major. The docking simulation with the target enzyme, sterol 14α-demethylase (CYP51) was performed using AutoDock 4.2 program.

Results: The IC (concentration of test compound required for 50% inhibition) against promastigotes revealed that luliconazole (IC=0.19μM) has greater potency than ketoconazole (KET), meglumine antimoniate (MA) and amphotericin B (AmB) (IC values of 135, 538 and 2.52μM, respectively). Against the amastigote stage, luliconazole at a concentration of 0.07μM decreased the mean infection rate and the mean number of amastigotes per macrophage more effectively than MA (P<0.004) and KET (P<0.043), but there was no difference compared with AmB (P>0.05). A docking study of luliconazole with the cytochrome P450 enzyme sterol 14α-demethylase (CYP51) revealed that this azole drug can properly interact with the target enzyme in Leishmania mainly via coordination with heme and multiple hydrophobic interactions.

Conclusion: These results show the potent activity of luliconazole at extremely low concentrations against L. major. It may therefore be considered as a new candidate for treatment of leishmaniasis in the near future.
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http://dx.doi.org/10.1016/j.jgar.2018.05.007DOI Listing
September 2018

Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates.

Antimicrob Agents Chemother 2018 05 26;62(5). Epub 2018 Apr 26.

Department of Medical Mycology/Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

The objective of this study was to assess the activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole, and fluconazole) against a large collection of and 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 and .
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http://dx.doi.org/10.1128/AAC.02423-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923135PMC
May 2018

Potent Activities of Luliconazole, Lanoconazole, and Eight Comparators against Molecularly Characterized Fusarium Species.

Antimicrob Agents Chemother 2018 05 26;62(5). Epub 2018 Apr 26.

Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

A collection of clinical ( = 47) and environmental ( = 79) 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 species.
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http://dx.doi.org/10.1128/AAC.00009-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923147PMC
May 2018