The first case of isolation of Magnusiomyces capitatus from the oral cavity of an addicted patient.

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast, rarely found as a causal agent of invasive fungal infection. In this study, we report a 31-year-old man infected with M. capitatus in the oral cavity, with a history of heroin and amphetamine abuse. M. capitatus was isolated through culture and microscopic analysis and identified by PCR amplification of the ITS DNA region. Based on the in vitro antifungal susceptibility test, the lowest MICs for M. capitatus were recorded for nystatin, itraconazole, and amphotericin, while higher MICs were observed for caspofungin and fluconazole. Treatment with nystatin successfully eliminated M. capitatus and relieved the clinical symptoms. This study presents the first case of M. capitatus in a patient with substance use disorder, manifesting as a plaque-like ulcer in the oral cavity.

Sheep serve as a reservoir of Trichophyton mentagrophytes genotype V infection.

Human infections by Trichophyton mentagrophytes occur mainly due to contact with diseased animals. In Iran, T. mentagrophytes genotype V is the most prevalent variant of the fungus. We aimed to determine the animal reservoir of T. mentagrophytes genotype V infection. The study was done on a total of 577 dermatophyte strains obtained from animals with signs of dermatophytosis and human patients. The list of extensively sampled animals included sheep, cows, cats and dogs. For human cases, epidemiological data were collected. All dermatophyte isolates from animals along with 70 human isolates morphologically similar to T. verrucosum and T. mentagrophytes genotype V were identified by rDNA internal transcribed spacer region restriction fragment length polymorphism analysis and DNA sequencing. A total of 334 animal dermatophyte strains were identified as Microsporum canis, T. mentagrophytes genotype V, T. verrucosum, Nannizzia gypsea, T. mentagrophytes genotype II*, T. mentagrophytes genotype VII, T. quinckeanum, and N. fulva. All clinical isolates identified as T. mentagrophytes genotype V originated from skin and scalp infections. Almost all veterinary isolates of T. mentagrophytes genotype V were cultured from sheep, but epidemiological data on animal-to-human transmission of T. mentagrophytes genotype V infection were limited and we found evidence in favor of interhuman transmission. In Iran, sheep maintain T. mentagrophytes genotype V population and therefore serve as animal reservoir of respective infections. The role of sheep as the source of human dermatophytosis due to T. mentagrophytes genotype V isolates is yet to be proven.

In this study, we sampled a variety of animals to determine a reservoir of Trichophyton mentagrophytes genotype V infection. With the use of molecular identification techniques, we show that this infection reservoir is represented by sheep.

Low level of antifungal resistance in Candida species recovered from Iranian HIV-associated oral infection.

Oral candidiasis (OC) is the most frequent opportunistic fungal infection, which is a predictive indicator of immunosuppression and disease progression among people living with HIV/AIDS (PLWHA). In the present study, 109 Candida isolates were collected from 94 PLWHA afflicted with oral Candida infection (OCI) following highly active antiretroviral therapy (HAART). The susceptibility profiles of Candidaspp. to six antifungal agents were evaluated using CLSI broth microdilution. The prevalence of OCI was 34.06%. The susceptibility profile of Candidaspp. revealed 100% sensitivity to caspofungin, while 6.4%, 5.4%, 24.5%, and 2.8% of Candida isolates showed resistance or nonwild-type MICs to fluconazole, itraconazole, posaconazole, and amphotericin B, respectively. Notably, 15.9% of patients and 3.7% of isolates showed mixed Candida infections and multidrug resistance, respectively. The low-level resistance to antifungal agents observed in the present study may be explained by the fact that none of the participants had prior and prolonged exposure to these antifungals. However, more focus should be placed on the mechanisms of reduced susceptibility and low-level resistance in Candida species since they can serve as stepping stones to developing clinical resistance. Alongside this, it seems a must to understand the local epidemiology of Candida spp. and their susceptibility pattern.

Epidemiology and Antifungal Susceptibility of Candida Species Isolated from 10 Tertiary Care Hospitals in Iran.

In recent decades, the incidence of Candida infections has increased in immunocompromised patients. This multicenter study aimed to evaluate in vitro antifungal activities of 8 antifungal agents against the Candida species isolated from 10 university hospitals in Iran. During the period from Dec 2019 to Dec 2021, Candida species were collected from clinical samples of patients. The isolates were identified by PCR restriction fragment length polymorphism and sequencing methods. The antifungal susceptibility tests of each isolate to eight antifungal agents were performed according to the microdilution CLSI M27, M59, and M60 standard methods. A total of 598 Candida strains were isolated from clinical samples. The most commonly isolated Candida species was C. albicans, followed by C. glabrata, C. parapsilosis, Debaryomyces hansenii (Candida famata), C. tropicalis, Pichia kudriavzevii (Candida krusei), C. orthopsilosis, Meyerozyma guilliermondii (Candida guilliermondii), Kluyveromyces marxianus (Candida kefyr), and Clavispora lusitaniae (Candida lusitaniae). MIC90 values in all Candida species were as follows: 0.25 µg/mL for caspofungin and voriconazole; 0.5 µg/mL for amphotericin B and isavuconazole; 2 µg/mL for itraconazole, luliconazole, and posaconazole; and 16 µg/mL for fluconazole. Although 30/285 C. albicans, 15/31 C. hansenii, 3/12 M. guilliermondii, 67/125 C. glabrata, 5/15 P. kudriavzevii, 6/60 C. parapsilosis, and 5/23 C. tropicalis isolates were multiazole resistant with resistance to 2 to 4 azoles, pan-azole resistance was not observed. According to our data, Candida albicans and C. glabrata were the most frequent species isolated from clinical samples in Iran. Caspofungin and voriconazole, with lower MIC90 values, are the most effective than other antifungal agents for the treatment of Candida infections in this region. IMPORTANCE Candida species cause severe invasive infections of the heart, brain, eyes, bones, and other parts of the body. Knowledge of regional distributions of causative Candida agents and their antifungal susceptibility patterns can help to monitor resistance to antifungal agents of various species and support local and national surveillance programs. In the present study, C. albicans and C. glabrata were the most frequently isolated species from clinical samples in Iran. Increasing rates of non-albicans Candida isolates from the Iranian population should be looked at as alarming due to various levels of intrinsic MIC values or resistance to various antifungal drugs. Caspofungin and voriconazole are recommended over fluconazole for the treatment of Candida infections in the study region. However, amphotericin B and isavuconazole are also active against the most common Candida species isolated from patients. Pan azole-resistant Candida species were not observed in the present study.

Phenotype, genotype, and mating type determination in oral Candida albicans isolates from pediatric patients with neutropenia.

BACKGROUND: The most frequent species of Candida to infect and colonize patients with neutropenia is still Candida albicans. This study aimed to provide detailed information on the phenotype, genotype, and mating type of oral C. albicans isolated from neutropenic pediatric patients, and to investigate how these characteristics are related. METHODS: Two hundred fifty-four oral samples from patients under 18 years old with neutropenia and malignancies were collected from January to October 2021. Samples were cultured on CHROMagar Candida. Isolates of C. albicans were identified with the germ tube test, chlamydospore production on cornmeal agar, and PCR-RFLP. Genotyping of C. albicans isolates was carried out by amplifying the 25S rDNA gene with specific CAINT-L and CA-INT-R primers. MTLa1 and MTLα1 primers were used to identify each mating type. Yeast peptone dextrose supplemented with phloxine B was used to identify different phenotypes. RESULTS: Ninety-two (36%) patients were positive for C. albicans. The mean age of patients was 7.85. Fifty-three (58.9%) isolates demonstrated type A, 15 (16.7%) type B, 15 (16.7%) types D/E, and 7 (7.7%) type C. Three isolates each (3.3%) were homozygous for MTLa or homozygous for MTLα. All of the MTL-homozygous isolates were genotype A. There was a significant correlation between patients' underlying disease and genotype (p = 0.036). There was a significant correlation between mating type and genotype (p = 0.000). CONCLUSION: Most of the isolates exhibited a white phenotype, noted in the literature as the most virulent. Moreover, heterozygous strains were frequent and may play a role in Candida colonization.

Epidemiology, prevalence, and associated factors of oral candidiasis in HIV patients from southwest Iran in post-highly active antiretroviral therapy era.

Background: Oral candidiasis (OC) is one of the most common opportunistic fungal infections among people living with HIV/AIDS (PLWHA). The prevalence of OC and Candida profiles among HIV-infected patients might be changing in the era of Highly Active Antiretroviral Therapy (HAART). This study aimed to identify Candida spp., determine OC prevalence and associated risk factors for PLWHA. Materials and methods: Oral candidiasis prevalence was explored in oral swabs of 276 patients who referred for consultation at Behavioral Diseases Counseling Center (BDCC). Clinical symptoms, culture and molecular assays were used for OC detection. In statistical analysis, we assessed socio-demographic characteristics, clinical information and treatment history of some infections. Results: The overall prevalence of OC was 41%. Candida albicans (64.6%) was the most common species, followed by C. glabrata (26.5%) and C. dubliniensis (19.5%). Candida famata, C. africana, and C. stellatoidea as the first fungi isolated from OC in PLWHA from southwest Iran. In 36.3% of patients, mixed cultures of more than one species were observed. Body mass index (BMI) (OR = 0.947; CI = 0.89-0.99; p = 0.045) and CD4 count ≤ 200 cells/mm3 (OR = 4.365; CI = 1.73-10.98; p = 0.002) were the predictors of OC in the final model of multiple logistic regression analysis. Education level, addiction status, sexual behaviors, chest X-ray, other infections and WHO clinical stage were other important risk factors for OC. Conclusion: Oral candidiasis remains a significant opportunistic infection in post-HAART era among PLWHA. Despite the increasing prevalence of NAC species, C. albicans (64.6%) was still the predominant species. Our results showed that low BMI with OC indicates treatment failure (i.e., failure to increase CD4 count or suppress viral load). Also, low CD4 counts (≤200 cells/mm3) in HIV patients show an impaired immune status, and our findings emphasize that OC can be a clinical indicator of HIV infection in individuals who do not know their HIV status or have failed treatment.

Evaluation of catalase activity of clinical and environmental isolates of Aspergillus species.

Background and Objectives: Catalases are a good scavenger of H2O2 which degrades hydrogen peroxide into water and oxygen. They are considered as a virulence factor that are present in both spores and hypha of fungi. There is limited data regarding catalase activity in Aspergillus species. This study aimed to assess the mycelial catalase activity of clinical and environmental isolates of Aspergillus niger, A. tubingensis, A. flavus, A. luchuensis, A. piperis and A. terreus. Materials and Methods: Briefly, clinical and environmental Aspergillus species were used in the current study. Catalase activity was assessed for both groups of isolates including 13 A. flavus (12 clinical, 1 environmental), 13 A. terreus (8 clinical, 5 environmental), 26 A. tubingensis (13 clinical, 13 environmental), and 44 A. niger (25 environmental, 19 clinical) species. Fungal balls of mycelia were separated from the liquid culture and were crushed using homogenizer. The supernatants were collected and used for a catalase activity assay. Results: Totally, in our study 98 Aspergillus including 45 environmental and 53 clinical isolates were assessed for catalase activity. High catalase activity was detected among environmental Aspergillus species (Mean= 1.62 mU/ml) and the mean of mycelial catalase activity among clinical A. terreus isolates was higher than environmental strains. Conclusion: In summary, mycelial catalase activity varied among species and environmental isolates demonstrated higher catalase activity. Totally a significant difference was found between clinical and environmental Aspergillus isolates.

Multicenter Study of Susceptibility of Aspergillus Species Isolated from Iranian University Hospitals to Seven Antifungal Agents.

Aspergillus species are a major cause of life-threatening invasive infections and noninvasive diseases. This study seeks to investigate the frequency of Aspergillus species among Iranian patients and their susceptibility to seven antifungals. In a cross-sectional study, 233 Aspergillus isolates were collected from 11 university hospitals in Iran between 2018 and 2021. Aspergillus isolates were identified based on colony morphology, microscopic characteristics, PCR-restriction fragment length polymorphism (RFLP), and sequencing of the beta-tubulin gene. The CLSI M38-A2 reference methodology was used for antifungal susceptibility testing of amphotericin B, voriconazole, posaconazole, itraconazole, luliconazole, isavuconazole, and caspofungin. Members of Aspergillus section Flavi (117/233, 50.2%), Aspergillus section Nigri (77/233, 33.1%), Aspergillus section Fumigati (21/233, 9%), Aspergillus section Terrei (14/233, 6%), Aspergillus pseudodeflectus (2/233, 0.85%), and Aspergillus melleus (2/233, 0.85%) were isolated from the samples. The lowest 0.25 MIC90 values for all isolates tested were for luliconazole (0.016 µg/mL) and isavuconazole (0.250 µg/mL), and the highest value was observed for itraconazole (≥ 8µg/mL). The 90% minimum effective concentration (MEC90) value for caspofungin was 0.125 µg/mL. MIC90 values for voriconazole, amphotericin B, and posaconazole were 1, 2, and 2 µg/mL, respectively. The non-wild-type species were presented for amphotericin B (3%), voriconazole (1.3%), posaconazole (2.6%), luliconazole (1.3%), isavuconazole (1.7%), and caspofungin (4.7%). Positive correlations in the MIC values of azole antifungals were observed, and using one azole increases the MIC value rates of other ones. None of the species were pan-azole resistant. Species of Aspergillus section Flavi were the most common Aspergillus species isolated from Iranian samples. Luliconazole, caspofungin, and isavuconazole present the most effective antifungal agents for treatment of infection due to Aspergillus species. Susceptibility tests should be performed frequently in each region for the best management of patients. IMPORTANCE Aspergillus species are the leading cause of invasive aspergillosis in immunocompromised hosts. The susceptibility of Aspergillus species to antifungal agents might be different. Azole-resistant species have emerged worldwide. Performing susceptibility testing in each region can help in the best management of patients. Here, we show the epidemiology and distribution of Aspergillus species in Iran and their susceptibility patterns for seven antifungal agents. The significant points of the present study are that species of Aspergillus section Flavi are the most prevalent Aspergillus species isolated from 11 university hospitals. Luliconazole, caspofungin, and isavuconazole were effective antifungal agents against all Aspergillus species.

ABC typing and extracellular enzyme production of Candida albicans isolated from Candida vulvovaginitis.

BACKGROUND: Candida albicans is the most common and virulent genus Candida. Detection of virulence factors in this species plays an important role in the better understanding of pathogenesis and antifungal treatment. Molecular typing investigations are important in the epidemiological interpretation of infection. This study aimed to evaluate extracellular enzyme activity and genotyping of C. albicans species isolated from vulvovaginal samples. METHODS: One hundred and three vaginal C. albicans isolates were tested for esterase, phospholipase, proteinase, and hemolysin activities by specific media. Besides, the DNA of C. albicans isolates was extracted and amplified for ABC genotyping. RESULTS: The highest enzyme production of C. albicans isolates was for proteinase (97.1%) and esterase (95.2%), whereas 59.2% of C. albicans isolates were negative for hemolysin secretion. Genotype C (83.5%) was the most frequent genotype followed by genotype B (12.6%) and genotype A (3.9%). CONCLUSION: It is concluded that genotype C was the predominant genotype in all examined vulvovaginal C. albicans isolates. Also, there was a significant difference between enzyme production in each genotype (except for proteinase).

In vitro activities of 8 antifungal agents against geophilic dermatophyte isolates.

BACKGROUND: Members of the Nannizzia gypsea complex are globally the most common geophilic dermatophytes which cause infection in animals and human. Although the susceptibility patterns of anthropophilic or zoophilic dermatophyte species to antifungal agents are well documented, the effectiveness of such drugs against geophilic species have rarely been explored. OBJECTIVES: This study was aimed to evaluate the in vitro antifungal activity of common and new antifungals against a set of environmental and clinical geophilic dermatophyte isolates. METHODS: 108 soil and clinical geophilic isolates from two genera Nannizzia (N. fulva n = 59; N. gypsea n = 43) and Arthroderma (A. quadrifidum n = 4; A. gertleri n = 1; A. tuberculatum n = 1) were included in the study. The in vitro antifungal susceptibility patterns of eight common and new antifungals against the isolates were determined according to broth microdilution method and by CLSI M38-A3 (3rd edition) protocol. RESULTS: MIC values across all isolates from five species ranged as: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.125-1 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml, griseofulvin: 0.25-2 µg/ml and tavaborole: 1-8 µg/ml, respectively. CONCLUSION: Luliconazole, terbinafine and efinaconazole exhibited the highest in vitro efficacy, regardless of the dermatophyte species. Further surveillance studies are recommended to confirm the implication of such in vitro data for the clinical recovery rate of dermatophytosis with geophilic species following antifungal therapy.

A comparative study on the production of extracellular hydrolytic enzymes of C. albicans and non-albicans Candida species isolated from HIV+/AIDS patients and healthy individuals.

Background and Purpose: Oropharyngeal candidiasis is the most prevalent opportunistic fungal infection in patients with human immunodeficiency virus (HIV) as well as other immunodeficiency disorders, which is caused by various Candida species, mostly Candida albicans. Studies have shown that Candida isolates differ in their pathogenicity. These variations are attributed to virulence factors, host characteristics, and the target tissue. This study aimed to determine and compare the secretion of hydrolytic enzymes in C. albicans and non-albicans Candida species isolated from HIV+/AIDS patients and healthy individuals. Materials and Methods: Samples were taken from 201 patients with HIV and 118 healthy individuals. The samples were identified by macroscopic, phenotypic, and molecular methods, and virulence factors were subsequently measured. Statistical differences in enzymatic activity of various Candida isolates were calculated (P<0.0001). Results: In total, 95 samples (47.20%) from patients and 46 samples (38.90%) from healthy individuals were positive for the growth of different Candida species. There were 39 (41.10%) and 36 (78.30%) C. albicans in patients and healthy individuals, respectively, as well as 56 (58.90%) and 10 (21.70%) non-albicans species in patients and healthy subjects, respectively. All the enzymes produced by Candida species enzymes were at low, medium, and high levels. Hemolysin activity in Candida species isolated from patients was significantly higher, compared to healthy individuals. Moreover, the activity of all C. albicans enzymes in patients was significantly higher than other Candida species. Conclusion: The C. albicans isolated from HIV-positive individuals secreted higher amounts of exoenzymes, and can cause oropharyngeal candidiasis and become a source of candidiasis for the host.

Pediatric candiduria, epidemiology, genotype distribution and virulence factors of Candida albicans.

The presence of Candida species in urine may be due to colonization of this species in the bladder, urinary catheter, and perineum. Candida albicans has been the most commonly isolated from urine samples in patients with candiduria. Several virulence factors include adhesion to host cells, secreted extracellular enzymes, phenotype switching, and biofilm formation are contributing to the pathogenicity of C. albicans. ABC genotyping is the method based on the determination of 25s rDNA and C. albicans is divided into four genotypes include A, B, C, and E. We aimed to identify Candida species from pediatrics and evaluate extracellular enzyme activities, phenotype switching, biofilm formation, and genotyping in isolates. Urine samples collected, cultured, and yielded yeasts were identified. Phenotype switching, biofilm formation, enzymatic patterns, and genotyping of 50 isolates of C. albicans were evaluated. The Genotyping pattern was compared with extracellular enzymes, biofilm formation, and phenotype switching pattern. 16.2% of urine cultures were positive for the different Candida species. The most common species was C. albicans, followed by C. glabrata. Out of 50 isolates of C. albicans, 72% and 28% isolates were recognized as genotypes A and C. All isolates were produced extracellular enzymes and biofilm formation. In conclusion, candiduria with high colony counts is still a challenge in Iranian pediatrics. Genotype A was the predominant genotype among C. albicans strains. There is a statistical difference between esterase and genotypes of C and A C. albicans.

In vitro antifungal susceptibility patterns of Trichophyton benhamiae complex isolates from diverse origin.

BACKGROUND: Species from the Trichophyton benhamiae complex are mostly zoophilic dermatophytes which cause inflammatory dermatophytosis in animals and humans worldwide. OBJECTIVES: This study was purposed to (a) to identify 169 reference and clinical dermatophyte strains from the T benhamiae complex species by molecular method and adhering to the newest taxonomy in the complex (b) to evaluate the in vitro antifungal susceptibility profile of these strains against eight common and new antifungal agents that may be used for the treatment of dermatophytosis. METHODS: All isolates, mainly originated from Europe but also from Iran, Japan and USA, were subjected to ITS-rDNA sequencing. The in vitro antifungal susceptibility profiles of eight common and new antifungal drugs against the isolates were determined by CLSI M38-A2 protocol and according to microdilution method. RESULTS: Based on the ITS-rDNA sequencing, T benhamiae was the dominant species (n = 102), followed by T europaeum (n = 29), T erinacei (n = 23), T japonicum (n = 10), Trichophyton sp (n = 4) and T eriotrephon (n = 1). MIC ranges across all isolates were as follows: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.06-2 µg/ml, griseofulvin: 0.25-4 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml and tavaborole: 1-16 µg/ml. CONCLUSION: Luliconazole, efinaconazole and terbinafine were the most potent antifungals against T benhamiae complex isolates, regardless of the geographic locations where strains were isolated. These data might help dermatologists to develop effective therapies for successful treatment of infections due to T benhamiae complex species.

Applications of western blot technique: From bench to bedside.

Western blot (WB) or immunoblot is a workhorse method. It is commonly used by biologists for study of different aspects of protein biomolecules. In addition, it has been widely used in disease diagnosis. Despite some limitations such as long time, different applications of WB have not been limited. In the present review, we have summarized scientific and clinical applications of WB. In addition, we described some new generation of WB techniques.

Molecular identification, biofilm formation and antifungal susceptibility of Rhodotorula spp.

Luliconazole is an imidazole antifungal agent used in topical form for the treatment of onychomycosis and dermatophytosis. In vitro activity of luliconazole against dermatophytes, Candida, black fungi, Fusarium and Aspergillus species have been investigated. Rhodotorula spp. are environmental yeasts and emerged as opportunistic pathogens among immunocompromised patients. Rhodotorula's human infections are usually resistant to treatment with antifungal drugs especially triazoles and echinocandins. The present study aimed at the molecular detection of environmental isolates of Rhodotorula spp. Then, antifungal efficacy of luliconazole was evaluated against isolates and compared to other routine systemic antifungals including; caspofungin, posaconazole, fluconazole, itraconazole, amphotericin B, and voriconazole. The biofilm production of Rhodotorula isolates was also evaluated. In this study, 39 isolates of Rhodotorula spp. were isolated from the environment, detected using molecular methods, and tested against luliconazole. Then, the anti-fungal activity of luliconazole compared with several routine antifungals. Also, biofilm formation by using a crystal violet staining assay was performed. Our finding showed that luliconazole has a very high minimum inhibitory concentration (MIC) value (1-8 µg/ml) against Rhodotorula spp. Besides, 100% of Rhodotorula strains were resistant to caspofungin, followed by fluconazole 94.7% and voriconazole 74.4%. Amphotericin B was demonstrated excellent in vitro activity against this genus. Our result indicated that 59% of Rhodotorula spp. were in the mid-range of biofilm production. Our results indicated that luliconazole does not effective against the genus Rhodotorula. Furthermore, amphotericin B is the best drug against this genus in comparison to caspofungin and other azole drugs.

Luliconazole, a highly effective imidazole, against Fusarium species complexes.

Luliconazole is a new antifungal that was primarily used for the treatment of dermatophytosis. However, some studies have shown that it has excellent efficacy against Aspergillus and Candida species in vitro. The present study aimed to evaluate of luliconazole activity against some Fusarium species complex isolates. In this study, 47 isolates of Fusarium were tested against several antifungals including luliconazole. All species were identified using morphology features, and PCR sequencing and antifungal susceptibility were performed according to CLSIM38 A3 guideline. Our results revealed that luliconazole has a very low minimum inhibitory concentration value (0.0078-1 µg/ml) in comparison with other tested antifungals. Amphotericin B had a poor effect with a high MIC90 (64 µg/ml), followed by terbinafine (32 µg/ml), posaconazole (16 µg/ml), caspofungin (16 µg/ml), voriconazole (4 µg/ml), and itraconazole (4 µg/ml). Overall, our findings indicated that luliconazole has great activity against environmental and clinical Fusarium species complexes in comparison to tested antifungals.

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

INTRODUCTION: Trichophyton mentagrophytes and T. interdigitale 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 T. interdigitale and 45 T. mentagrophytes 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 (SQLE) 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 T. mentagrophytes and T. interdigitale isolates. There were five isolates with terbinafine MICs ≥32 µg/mL in our sample. They belonged to T. mentagrophytes type VIII and harbored two alternative SQLE 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 T. mentagrophytes. However, treatment alternatives for resistant isolates were available.

In vitro antifungal susceptibilities of six antifungal drugs against clinical Candida glabrata isolates according to EUCAST.

BACKGROUND AND PURPOSE: Candida glabrata is the second cause of candidiasis. The mortality rate of C. glabrata infections is about 40%; accordingly, it may be life threatening, especially in immunocompromised hosts. Regarding this, the current study was conducted to evaluate the regional patterns of the antifungal susceptibility of clinical C. glabrataisolated from the patients referring to the health centers located in Ahvaz, Iran. MATERIALS AND METHODS: In this study, a total of 30 clinical strains of C. glabrata isolates were recovered from different body sites (i.e., vagina, mouth, and urine). Phenotypic characteristics and molecular methods were used to identify the isolates. The minimum inhibitory concentration (MIC) was determined according to the European Committee on Antimicrobial Susceptibility Testing. RESULTS: Our findings demonstrated that 20%, 80%, and 6.7% of the isolates were resistant to amphotericin B, terbinafine, and posaconazole, respectively, while all the isolates were found to be fluconazole susceptible dose dependent and susceptible to voriconazole and caspofungin. CONCLUSION: Our study suggested that voriconazole had high potency against C. glabrata isolates. Consequently, this antifungal agent can be an alternative drug in the treatment of resistant patients. These results can be helpful for the successful treatment of patients in different regions.

Antifungal susceptibility profiles of otomycosis etiological agents in Ahvaz, Iran.

BACKGROUND AND PURPOSE: Otomycosis is a secondary ear fungal infection among predisposed individuals in humid conditions. Aspergillus species are the most common etiologic agents of this infection. Several ototopical antifungals are currently used for the treatment of this disease; however, recurrence and treatment failure are usually observed in some cases. Regarding this, the present study was conducted to investigate the antifungal activity of caspofungin, azoles, and terbinafine against the isolated agents of otomycosis. MATERIALS AND METHODS: This study was conducted on the specimens collected from 90 patients with otomycosis. The samples were cultured on Sabouraud dextrose agar and identified based on morphological characteristics, physiological tests, and microscopic features. Furthermore, the microdilution method was used for antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Finally, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC) ranges, MIC/MEC50, MIC/MEC90, and geometric mean (GM) MIC/MEC were calculated for the isolates. RESULTS: According to the results, 77 patients with otomycosis were positive for different Aspergillus (88.3%) and Candida (11.7%) species. Aspergillus niger complex (n=36) was found to be the most common agent, followed by A. flavus, A. terreus, and A. nidulans complexes. Furthermore, epidemiological cutoff values (ECVs) were lower than those presented by the CLSI for itraconazole and caspofungin in 98.5% and 42.6% of Aspergillus species, respectively. Terbinafine exhibited a great activity against Aspergillus species, while fluconazole revealed a low activity against both Aspergillus species. Based on the results, 77.8% of Candida species were resistant to caspofungin; however, miconazole and econazole had low MIC ranges. CONCLUSION: Aspergillus niger and A. flavus complexes were identified as the most common agents accounting for 85.7% of the isolates. In addition, terbinafine was identified as the best antifungal for both Aspergillus and Candida species. Moreover, tested azoles had relatively low MICs, whereas most of the isolates had the MIC values beyond the caspofungin ECVs.