Onychomycosis due to Fusarium species in different continents, literature review on diagnosis and treatment.

Fusarium species are an emerging cause of onychomycosis, and the number of cases has dramatically increased in recent decades worldwide. This review presents an overview of the onychomycosis cases caused by Fusarium species and diagnosis and treatment that have been reported in the literature. The most common causative agent of onychomycosis is F. solani species complex, which accounts for 11.68% of the cases of Fusarium onychomycosis, followed by the F. oxysporum species complex (164 out of 1669), which is accounted for 9.83% of the total. F. fujikuroi species complex (42 out of 1669) and F. dimerum species complex (7 out of 1669) are responsible for 2.52% and 0.42 cases, respectively. Fusarium nail infections were reported in patients aged range 1-98, accounting for 5.55% (1669 out of 30082) of all cases. Asia has the highest species diversity of Fusarium onychomycosis (31.51%). South America accounts for 21.09%, and the most common causative agent is F. solani (19.32%), followed by F. oxysporum species complex (15.63%). Europe accounts for 4.90% of cases caused by F. oxysporum, followed by F. solani. Africa accounts for 23.87% of the cases due to the F. solani species complex, followed by F. oxysporum and F. fujikuroi. Distal and lateral subungual onychomycosis was the most common clinical symptom accounting for 58.7% (135 out of 230) of the cases. Data analysis relieved that terbinafine and itraconazole are active treatments for Fusarium onychomycosis. For a definitive diagnosis, combining of direct examination, culture and sequencing of the elongation factor of translation 1α are recommended. Accurate identification of the causative agents of onychomycosis due to Fusarium species and antifungal susceptibility testing is essential in patient management.

Molecular Epidemiology and Antifungal Susceptibility Profile in Nakaseomyces glabrata Species Complex: A 5-Year Countrywide Study.

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

High Prevalence of Terbinafine Resistance Among Trichophyton mentagrophytes/T. interdigitale Species Complex, a Cross-Sectional Study from 2021 to 2022 in Northern Parts of Iran.

Treatment-resistant dermatophytosis caused by the members of the Trichophyton mentagrophytes/Trichophyton interdigitale species group (TMTISG) is increasing worldwide. We aimed to determine the prevalence of TMTISG in patients with dermatophytosis in two centers from north of Iran and detect the possible mutations in the squalene epoxidase (SQLE) gene in relevant terbinafine (TRB) resistant pathogenic isolates. From November 2021 to December 2022, 1960 patients suspected to dermatophytosis and referred to two mycology referral laboratories in the north of Iran were included in the study. Identification of all dermatophyte isolates was confirmed by RFLP of rDNA internal transcribed spacer (ITS) regions. Antifungal susceptibility testing against five common antifungals using the CLSI-M38-A3 protocol was performed. The TMTISG isolates resistant to TRB, were further analyzed to determine the possible mutations in the SQLE gene. Totally, 647 cases (33%) were positive for dermatophytosis of which 280 cases (43.3%) were identified as members of TMTISG. These were more frequently isolated from tinea corporis 131 (44.56%) and tinea cruris 116 (39.46%). Of 280 TMTISG isolates, 40 (14.3%) were resistant to TRB (MIC ≥ 4 µg/mL), all found to be T. indotineae in ITS sequencing. In SQLE sequencing 34 (85%) of TRB-resistant isolates had coincident mutations of Phe397Leu and Ala448Thr whereas four and two isolates had single mutations of Phe397Leu and Leu393Ser, respectively. Overall, the resistance of Iranian TMTISG isolates to TRB greatly occurred by a mutation of Phe397Leu in the SQLE gene as alone or in combination with Ala448Thr. Nevertheless, for the occurrence of in vitro resistance, only the presence of Phe397Leu mutation seems to be decisive.

In vitro antifungal susceptibility profile of Iranian Fusarium isolates: Emphasising on the potent inhibitory effect of efinaconazole compared to other drugs.

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

Central nervous system Aspergillus quadrilineatus infection in a COVID-19 patient, a case report and literature review.

BACKGROUND: Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients. METHODS: Here we report a pediatric case of Aspergillus quadrilineatus cerebral infection in a recently diagnosed COVID-19-positive patient underlying acute lymphocytic leukemia. Morphological, molecular methods, and sequencing were used to identify this emerging species. RESULTS: Histopathological examination showed a granulomatous necrotic area containing dichotomously branching septate hyphae indicating a presumptive Aspergillus structure. The species-level identity of isolate growing on brain biopsy culture was confirmed by PCR sequencing of the ß-tubulin gene as A. quadrilineatus. Using the CLSI M38-A3 broth microdilution methodology, the in vitro antifungal susceptibility testing demonstrated 0.032 µg/mL MIC for posaconazole, caspofungin, and anidulafungin and 8 µg/mL against amphotericin B. A combination of intravenous liposomal amphotericin B and caspofungin therapy for 8 days did not improve the patient's condition. The patient gradually continued to deteriorate and expired. CONCLUSIONS: This is the first COVID-19-associated cerebral aspergillosis due to A. quadrilineatus in a pediatric patient with acute lymphocytic leukemia. However, comprehensive screening studies are highly recommended to evaluate its frequency and antifungal susceptibility profiles. Before being recommended as first-line therapy in high-risk patients, more antifungal susceptibility data are needed.

In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis.

Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.84 Aspergillus species with high MIC values to terbinafine (≥ 4 µg/ml), consisting of A. flavus, A. tubingensis, A. niger, and A. terreus, were included in this study. The checkerboard microdilution method evaluated the in vitro interactions using the CLSI reference technique. Synergistic effects were observed for 66.67% (56/84) of all isolates (FICI ranging from 0.19 to 0.5). However, the interactions of terbinafine and ketoconazole exhibited indifference in 33.33% (28/84) of the isolates, and no antagonism was observed for any combination. The interaction of terbinafine and ketoconazole showed synergistic activity against Aspergillus species with high MIC values, suggesting that this is an alternative and promising approach for treating otomycosis.

Iranian National Survey on Tinea Capitis: Antifungal Susceptibility Profile, Epidemiological Characteristics, and Report of Two Strains with a Novel Mutation in SQLE Gene with Homology Modeling.

BACKGROUND: The data on the epidemiological and antifungal susceptibility profile of tinea capitis (TC) in Iran has not been updated in recent decades. This report presents the Iranian epidemiological and drug susceptibility data regarding the distribution of dermatophytes species isolated by six national mycology centers for a period of one year (2020-2021). MATERIAL AND METHODS: A total of 2100 clinical samples from individuals suspeted to TC were subjected to mycological analysis of direct microscopy and culture. For definite species identification, the culture isolates were additionally subjected to PCR-RFLP and PCR-sequencing of the ITS ribosomal DNA (ITS-rDNA) region. Antifungal susceptibility profiles for eight common antifungal drugs were determined by CLSI M38-A3 guidelines. The SQLE gene was partially amplified and sequenced in two terbinafine-resistant and two susceptible T. mentagrophytes isolates to elucidate probable substitutions involved in resistance. RESULTS: TC (n = 94) was diagnosed in 75 children (79.8%) and 19 adults (20.2%) by direct microscopy and culture. Frequency of TC was significantly more among males (66 males = 70.2% vs 28 females = 29.8%). The prevalent age group affected was 5-9 years (39.36%). Thirty-two (34.04%) T. mentagrophytes, 27 (28.7%) T. tonsurans, 14 (14.9%) M. canis, 13 (13.8%) T. violaceum, 5 (5.32%) T. indotineae, 2 (2.1%) T. benhamiae, and 1 (1.1%) T. schoenleinii were identified as the causative agents. MIC values of isolates showed susceptibility to all antifungal agents, except for fluconazole and griseofulvin with GM MIC of 11.91 µg/ml and 2.01 µg/ml, respectively. Terbinafine exhibited more activity against isolates, with GM MIC 0.084 µg/ml followed by ketoconazole (0.100 µg/ml), econazole (0.107 µg/ml), itraconazole (0.133 µg/ml), butenafine (0.142 µg/ml), and miconazole (0.325 µg/ml). Two resistant T. mentagrophytes isolates harbored missense mutations in SQLE gene, corresponding to amino acid substitution F397L. Remarkably, one unique mutation, C1255T, in the SQLE sequence of two terbinafine-susceptible T. mentagrophytes strains leading to a change of leucine at the 419th position to phenylalanine (L419F) was detected. CONCLUSIONS: T. mentagrophytes, T. tonsurans, and M. canis remained the main agents of TC in Iran, however less known species such as T. indotinea and T. benhamiae are emerging as new ones. Terbinafine could still be the appropriate choice for the treatment of diverse forms of TC.

Impact of Negative Fluid Balance on Mortality and Outcome of Patients with Confirmed COVID-19.

Purpose: Maintaining the proper fluid balance is a fundamental step in the management of hospitalized patients. The current study evaluated the impact of negative fluid balance on outcomes of patients with confirmed COVID-19. Methods: We considered the negative fluid balance as a higher output fluid compared to the input fluid. The fluid balance was categorized into four groups (group 4: -850 to -500 ml/day; group 3: -499 to -200 ml/day, group 2: -199 to 0 ml/day, and group 1 : 1 to 1000 ml/day) and included ordinally in the model. The outcomes were all-cause mortality, length of hospitalization, and improvement in oxygen saturation. Results: The fluid balance differed significantly among nonsurvivors and survivors (MD: -317.93, 95% CI: -410.21, -225.69, and p < 0.001). After adjusting for potential confounders, there was a significantly lower frequency of mortality in patients with negative fluid balance compared to the controls (aRR: 0.69, 95% CI: 0.57, 0.84, and p < 0.001). Similarly, the length of hospitalization was significantly shorter in the negative fluid balance group in comparison to the control group (aMD: -1.01, 95% CI: -1.74, -0.28, and p=0.006). Conclusion: We determined that the negative fluid balance was associated with favorable outcomes in COVID-19 patients. The negative fluid balance was associated with the reduced mortality rate and length of hospitalization as well as improvement in oxygen saturation. Moreover, the NT-proBNP >781 pg/mL and fluid balance >-430 mL might be the predictors for positive fluid balance and mortality, respectively.

Prevalence, genetic diversity and antifungal susceptibility profiles of F. fujikuroi, F. solani and Fusarium incarnatum-equiseti species complexes from onychomycosis in north of Iran.

Onychomycosis, a nail fungal infection, is normally caused by dermatophytes. However, yeasts and non-dermatophyte moulds (NDM) are among pathogens that cause nail disease. Regarding, this study aimed to describe the molecular epidemiology of Fusarium onychomycosis in the North of Iran. Two hundred and fifty seven nail samples collected from the patients clinically suspected of onychomycosis were subjected to direct microscopy, calcofluor white staining and culture. Fusarium isolates were identified at a species level through determination of multi-locus sequences for internal transcribed spacer and translation elongation factor 1 alpha. Based on the findings, Fusarium species were isolated from onychomycosis patients (n = 27). According to a previous partial genes analysis, the species in the recent study belonged to the members of F. fujikuroi species complex (n = 14), Fusarium incarnatum-equiseti species complex (n = 1) and F. solani species complex (n = 12). In this study, F. proliferatum was the dominant Fusarium species collected from the samples. The correct identification of Fusarium species is essential regarding the increased prevalence of Fusarium onychomycosis and the inherent resistance of these agents to a wide spectrum of antifungals. The obtained results indicated variation in the epidemiology of Fusarium species isolated from onychomycosis. Moreover, the minimum inhibitory concentration (MIC) of luliconazole and lanoconazole was in the range of 0.001-1 µg/ml, with the geometric mean of MICs obtained at 0.0103 and 0.0343 µg/ml against Fusarium species, respectively. These findings can increase researchers' knowledge regarding diversity of species, distribution of onychomycosis and the choice of a proper treatment.

In vitro activity of 23 antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates.

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

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

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.

First molecular report of causative agent of otomycosis due to Aspergillus luchuensis.

Otomycosis is a fungal infection of the external auditory canal caused mainly by the genus Aspergillus. Aspergillus luchuensis, an industrially important fungus, is a member of Aspergillus section Nigri. In this report, we present a case of otomycosis due to Aspergillus luchuensis in a 43-year-old female patient. We performed a partial PCR-sequencing of ß-tubulin and calmodulin genes to identify the isolate to the species level. Further, we determined the in vitro susceptibility of the isolate to nystatin, clotrimazole and itraconazole according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 protocol. Accordingly, the minimum inhibitory concentrations of clotrimazole, nystatin and itraconazole were 0.25µg/mL, 0.5µg/mL and 1µg/mL, respectively. This is the first report of clinically relevant isolation of Aspergillus luchuensis identified by a molecular technique as a causative agent of otomycosis.

Molecular identification and antifungal susceptibility of clinical fungal isolates from onychomycosis (uncommon and emerging species).

Onychomycosis is a common nail problem, accounting for up to 50% of all nail diseases. The aim of the present study was to determine the species distribution based on the restriction fragment length polymorphism and susceptibility patterns of the causative agents of onychomycosis. This cross-sectional study was conducted on nail samples collected from 257 patients suspected of onychomycosis during 14 months. Fungal isolates were identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) with the enzymes Msp I, Mva I, Alw I and sequencing. According to the results, out of the 257 patients participating in the study, onychomycosis was diagnosed in 180 (70.03%) cases, among which 51.1% were caused by non-dermatophyte moulds (NDMs), 35% by yeast and 10.6% by dermatophytes. Numerous cryptic species recovered from onychomycosis for the first time. In the majority of cases, novel triazoles and imidazoles (ie, efinaconazole, luliconazole and lanoconazole) showed potent activity in comparison with other antifungal agents. The minimum inhibitory concentration (MIC) of luliconazole and lanoconazole ranged within 0.001 to >1 µg/mL and their geometric mean MICs were 0.0154 and 0.0309 µg/mL against all isolates, respectively. It seems that obtained data will be useful to improve the knowledge of researchers, clinicians and dermatologists about onychomycosis distribution, species diversity and adoption of appropriate treatment.

Estimated burden of serious human fungal diseases in Turkey.

The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017 and modelling previously described by the LIFE program (http://www.LIFE-worldwide.org). Among the population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%) people are estimated to suffer from a serious fungal infection each year. The model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989 cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases) (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000). The estimated annual incidence for invasive aspergillosis is lower (3911 cases) (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100 000) females. The burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis (1.73 million). Given that the modelling estimates reported in the current study might be substantially under- or overestimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates.

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

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.

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

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

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

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

Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates.

Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial ß-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus 2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatest in vitro activity among systemic azoles and echinocandins, respectively. However, the majority of the A. flavus isolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility of A. flavus was not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.

The First Case of Total Dystrophic Onychomycosis Caused by Aspergillus clavatus Resistant to Antifungal Drugs.

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

Multi-drug resistance Trichophyton indotineae in a stray dog.

A 2.5-year-old stray dog showed signs of hair loss, mild skin crusting, and redness on extremities and trunk. The etiologic agent was confirmed as Trichophyton indotineae by sequencing of ITS region. Using the Clinical and Laboratory Standards Institute (CLSI M38-A3) guideline, antifungal susceptibility testing showed multidrug resistance phenotype against terbinafine (16 µg/mL-1), itraconazole, and some other tested antifungals (minimum inhibitory concentration, MIC≥16 µg/mL-1). However, luliconazole was found to be active in- vitro (0.016 µg/mL-1). Upon further studies, sequencing of SQLE gene showed an amino acids substitution of Phe397Leu and Ala448Thr, which is potentially linked to terbinafine resistance in Trichophyton species.