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In vitro susceptibility testing for Trichophyton rubrum has shown resistance to terbinafine, azoles and amorolfine, locally, but epidemiological cutoffs are not available. In order to assess the appropriateness of current first-line antifungal treatment for T. rubrum in China, we characterized antifungal susceptibility patterns of Chinese T. rubrum strains to nine antifungals and also described the upper limits of wild-type (WT) minimal inhibitory concentrations (MIC) (UL-WT) based on our study and another six studies published during the last decades. Sixty-two clinical isolates originating from seven provinces in China were identified as T. rubrum sensu stricto; all Chinese strains showed low MICs to eight out of nine antifungal drugs. Terbinafine (TBF) showed the lowest MICs of all antifungal classes tested in both the Chinese and global groups, with a 97.5% UL-WT MIC-value of 0.03 mg/L. No non-WT isolates were observed for TBF in China, but were reported in 18.5% of the global group. Our study indicated that TBF was still the most active drug for Chinese T. rubrum isolates, and all strains were within the WT-population. TBF therefore remains recommended for primary therapy to dermatophytosis caused by T. rubrum in China now, but regular surveillance of dermatophytes and antifungal susceptibility is recommended.

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063–0.5 µg/mL and 0.125–0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy. [ABSTRACT FROM AUTHOR]

Background: Otomycosis is considered a recurring fungal ear infection. The external auditory canal provides an appropriate and optimal situation for fungal growth. Objectives: The study aimed to identify the causative agents of otomycosis and determine corresponding antifungal drug susceptibility patterns in north‐western Iran. Methods: From October 2020 until November 2021, 200 patients attended an otolaryngology referral centre with otitis externa, and their ear discharge and debris were examined and cultured. The identification of the fungal agents was implemented by polymerase chain reaction‐restriction fragment length polymorphism and sequencing. In vitro antifungal susceptibility testing of the isolates was conducted in accordance with the CLSI broth microdilution protocols. Results: The prevalence of otomycosis was measured 50.5% (n = 101/200). The majority of patients were in their forties (n = 35, 34.6%) and female (n = 57, 56.4%), and the most prevalent symptom was otalgia (56.4%). The most underlying factor was remarked manipulation employing a cotton swab (65.3%). Regarding fungus, Aspergillus section Nigri (58.57%) was the foremost isolate, followed by Aspergillus section Flavi (19.23%) and Candida parapsilosis (14.96%). The predominance of Aspergillus isolates had minimal in vitro sensitivity to tioconazole and nystatin. Candida species represented higher geometric mean minimum inhibitory concentrations (MIC) against nystatin. The MIC of three Aspergillus species isolates shown above the epidemiologic cut‐off values (ECV) against itraconazole. Conclusions: Otomycosis incidence surpassed in comparison with the previous study as the most common cause of otitis externa. The MIC distribution of Aspergillus species isolates against triazole antifungals is close to the defined ECVs and likely outrun it over time. [ABSTRACT FROM AUTHOR]

Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study. [ABSTRACT FROM AUTHOR]

Effective management and treatment of fungal diseases is hampered by poor diagnosis, limited options for antifungal therapy, and the emergence of antifungal drug resistance. An understanding of molecular mechanisms contributing to resistance is essential to optimize the efficacy of currently available antifungals. In this perspective, one of the oldest antifungals, 5-fluorocytosine (5-FC), has been the focus of recent studies applying advanced genomic and transcriptomic techniques to decipher the order of events at the molecular level that lead to resistance. These studies have highlighted the complexity of resistance and provided new insights that are reviewed in the present paper. [ABSTRACT FROM AUTHOR]

Objective: Dirkmeia churashimaensis , belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents. Methods: An 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis , as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections. Results: Local barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn's disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections. Conclusions: The present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections. [ABSTRACT FROM AUTHOR]

Fusarium spp. are able to cause a wide range of opportunistic infections in both immunocompromised and immunocompetent individuals. Thus, new therapeutic options should be considered. We evaluated the antifungal activity of three phytocompounds (cinnamaldehyde, CIN; carvacrol, CRV; and thymol, THY), as well as their activities when combined with amphotericin B (AMB), caspofungin (CAS), itraconazole (ITC) and voriconazole (VRC) against 20 clinical isolates of Fusarium. Broth microdilution (M38-A2) and checkerboard methodologies were used to obtain MICs (Minimum inhibitory concentration) and FICIs (Fractional Inhibitory Concentration Index), respectively. The MICs observed for the phytocompounds were: 20–80 for CIN, 40-> 320 for CRV and 40–320 µg/mL for THY. The most effective combinations (synergism rates) were: THY + CAS (96%), CRV + CAS (88%), THY + AMB (76%), CRV + AMB (68%), THY + VRC (68%) and CRV + VRC (60%). Our findings suggest that CRV and THY have potent activity when combined with CAS, AMB or VRC. [ABSTRACT FROM AUTHOR]

Summary: Cryptococcus species are an encapsulated fungal pathogen that cause cryptococcal meningitis. There are limited therapeutic options for this infection. The management includes the use of different antifungals such as amphotericin B, flucytosine, or fluconazole, either alone or in combination. However, numerous therapeutic failures, as well as the limited effectiveness of such therapeutics, have been described. Diphenyl diselenide is a chemically synthesised molecule with was found to have antimicrobial activity. In this study, we evaluated the antifungal activities of fluconazole, amphotericin B and flucytosine, in combination with diphenyl diselenide against 30 clinical isolates of Cryptococcus spp. using CLSI M27‐A3 method and the checkerboard microdilution technique. Our results show that the combination of flucytosine and diphenyl diselenide displayed 100% of synergism. However, when we analysed (PhSe)2 plus AMB or FLZ we observed around 70% of indifference. Our results suggest that the combination of diphenyl diselenide with other antifungal agents deserves attention as a new option for the development of alternative therapies for cryptococcosis. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a life‐threatening mycosis primarily occurring in adult patients particularly those with immunosuppression such as HIV infection/AIDS. The number of reported cases of paediatric cryptococcosis has increased in the last decade around the world, including China. However, current information on the characteristics of cryptococcosis in children, particularly the genotypic diversity and antifungal susceptibility of the isolates, is limited. In the present study, a total of 25 paediatric isolates of Cryptococcus neoformans were genotyped using the ISHAM‐MLST scheme. In vitro susceptibility to antifungal agents of the 22 isolates was tested using the CLSI M27‐A3 method. Our analyses revealed that the genotypic diversity of C. neoformans isolates from Chinese paediatric patients was low, with ST 5 (80%) and ST 31 (12%) being the two major sequence types. Reduced susceptibility to fluconazole (FLU), 5‐flucytosine (5‐FC) and itraconazole (ITR) was observed among C. neoformans isolates from Chinese paediatric patients, particularly among the ST5 isolates, which was similar to observations made on C. neoformans isolates from Chinese adult patients. In addition, the majority of isolates (3/4, 75%) obtained from deceased patients showed decreased antifungal susceptibility, which indicates that further monitoring of antifungal susceptibility of Cryptococcus isolates is warranted in management of paediatric cryptococcosis. [ABSTRACT FROM AUTHOR]

In this study, we aimed to present the first molecular epidemiological data from Chennai, India, analyse keratitis cases that have been monitored in a university hospital during 2 years, identify the responsible Fusarium species and determine antifungal susceptibilities. A total of 10 cases of keratitis were included in the study. Fusarium isolates were identified using the second largest subunit of the RNA polymerase gene ( RPB2) and the translation elongation factor 1 alpha ( TEF1). Antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute ( CLSI) methodology. The aetiological agents belonged to Fusarium solani species complex ( FSSC) (n = 9) and Fusarium sambucinum species complex ( FSAMSC) (n = 1), and the identified species were Fusarium keratoplasticum (n = 7), Fusarium falciforme (n = 2) and Fusarium sporotrichioides (n = 1). All strains showed multidrug resistance to azoles and caspofungin but exhibited lower minimum inhibitory concentration ( MIC) to natamycin and amphotericin B. Fusarium keratoplasticum and Fusarium falciforme belonging to the Fusarium solani species complex were the major aetiological agents of Fusarium keratitis in this study. Early presentation and 5% topical natamycin was associated with better patient outcome. Preventative measures and monitoring of local epidemiological data play an important role in clinical practice. [ABSTRACT FROM AUTHOR]

The article focuses on the fungal genus Fusarium and the disease Fusariosis caused by it. Topics discussed include global distribution of genetically diverse Fusarium; impact on global economy due to various members of the genus that are pathogenic to plants and causes loss large amount of agriculturally important crops, its routes of human infection by inoculation, its resistance to antifungals, and treatment of fusariosis by drugs such as voriconazole and posaconazole.

Objectives: The aim of the present study was to evaluate and assess the in vitro activity of eight drugs, including the new azole isavuconazole, against 81 strains representing 13 species of the Fusarium fujikuroi species complex. Methods: A total of 81 Fusarium spp. isolates, within the F. fujikuroi species complex, were identified by molecular methods and tested according to CLSI M38-A2. Eight antifungal compounds, including the new azole isavuconazole, were tested. Isolates were selected to represent the widest variety of geographical regions and to include clinical as well as environmental strains. Results: Susceptibility profiles differed between and within species, with Fusarium verticillioides showing the lowest MICs and Fusarium nygamai the highest MICs. Amphotericin B was the most active drug, followed by voriconazole, posaconazole, isavuconazole and natamycin. The remaining antifungals (fluconazole, itraconazole and micafungin) showed poor activity with MIC/minimum effective concentration values of ≥32, ≥16 and >8 mg/L, respectively. Conclusions: Resistance patterns in the F. fujikuroi species complex are species specific and therefore identification down to species level is important for the choice of antifungal treatment. [ABSTRACT FROM AUTHOR]

Objectives: Fusarium species cause a broad spectrum of infections, from superficial to disseminated disease. Because Fusarium species are intrinsically resistant to most antifungal drugs, new approaches are needed. The aim of the present study was to evaluate the in vitro combination of natamycin with currently used antifungal drugs.Methods: The in vitro interactions of combinations between natamycin and voriconazole, itraconazole and micafungin applied to 20 clinical Fusarium strains (members of Fusarium falciforme, Fusarium napiforme, Fusarium petroliphilum, Fusarium proliferatum, Fusarium pseudensiforme and Fusarium sacchari) were evaluated using a chequerboard microdilution method. The MICs of all drugs alone and in combination were determined visually after 48 h and interactions were assessed using fractional inhibitory concentration index (FICI) analysis.Results: MICs of voriconazole and natamycin alone were 4 to >16 and 4-8 mg/L, respectively. Values were reduced 3.5-10-fold to 0.02-0.5 mg/L and 0.5-5-fold to 0.13-2 mg/L in combination, for the currently used antifungals and natamycin, respectively, demonstrating additive to synergistic interactions. The combinations natamycin/voriconazole, natamycin/itraconazole and natamycin/micafungin were synergistic (FICI ≤0.5) for 70%, 15% and 5% of the strains, respectively. No antagonism was found.Conclusions: The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations. [ABSTRACT FROM AUTHOR]