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Background: Nanostructured lipid carriers (NLCs) are emerging as the second generation of lipid nanoparticles to solve the shortcomings of the first generation (structured lipid carriers). Terbinafine hydrochloride is used to treat various fungal skin diseases. Objectives: The study’s main objective was to study the drug release and permeation between NLC and NLC-based gel formulation to select the better one. Methods: A central composite face-cantered (α=1) design with two components (the amount of liquid lipid and the homogenization speed) and 13 runs were used through Design-Expert® software (version 7.1.5). Terbinafine hydrochloride-loaded NLC (TH_NLC) was produced by using the hot-homogenization technique. Fourier transform infrared study was done to determine drug excipients’ compatibility. Dynamic light scattering (DLS) was employed to determine particle size. Utilizing scanning electron microscopy (SEM), the morphology and shape of the TH_NLC formulation were examined. The hydrogel was filled with the optimized products chosen by point prediction in design expert software. These products were assessed by their pH, spreadability, viscosity, homogeneity, extrudability, and drug content. The in vitro drug release study and the ex vivo permeation investigation for the optimized TH_NLCopt and TH_NLCopt gel formulation were carried out using Franz diffusion cells Results: The formulation contains nanoscale particles, as evidenced by the size range of the particles (17.57 to 329.4 nm). Entrapment efficiency was 60.95% and 98% for TH_NLCopt TH_NLCopt gel, respectively. Within 7 hours, 96.35% and 83.37% of the drug were released from optimized NLC and NLC-based gel, respectively. The amount of drug that had penetrated the skin in 7 hours ranged from 54.19% to 31.16%, with a retention range of 22.46% to 61.87%. Conclusion: The topical delivery of the TH_NLC-based gel system is quite promising.

Background: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine‐resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. Methods: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS‐PCR. Based on the culture‐positivity and prescribed systemic antifungal, patients were categorised into Group I culture‐positive cases treated with systemic terbinafine and Group II culture‐positive cases treated with systemic itraconazole, each for a total period of 12 weeks. Results: In the present study, 477 (81.39%) were culture‐positive; however, 12 weeks follow‐up was available for 294 patients (Group I‐157 and Group II‐137) who were included for statistical analysis. In both groups [Group I‐37/63 (51.4%) and Group II‐14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8–12 weeks, the odds of cure rate are significantly better (p <.001) with either itraconazole (Odd Ratio‐15.5) or terbinafine (Odd Ratio‐4.34). Higher MICs for terbinafine were noted in 41 cases (cured‐18 and uncured‐23) in Group I and 39 cases (cured‐16 and uncured‐23) in Group II. From cured (Group I‐17/18; 94.4% and Group II‐14/16; 87.5%) and uncured (Group I‐20/23; 86.9% and Group II‐21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 μg/mL (Group I‐p =.712 and Group II‐p =.69). Conclusion: This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis. [ABSTRACT FROM AUTHOR]

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion There is a recent growing global concern regarding the rise in antifungal resistance of dermatophytosis. The emergence of terbinafine‐resistant Trichophyton indotineae (T. indotineae), previously known as Trichophyton mentagrophytes genotype VIII, is particularly alarming given that terbinafine is considered the treatment of choice for dermatophyte infections and the limited number of available antimycotics. This strain surfaced in the Indian subcontinent in the mid‐2010s and more recently there have been reports of its arrival in Europe.The objective of this review is to document the presence of terbinafine‐resistant T. indotineae in Europe with the aim to guide antifungal stewardship and ultimately prevent the spread of resistance.This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A systematic literature search was performed using PubMed, Scopus and Web of Science databases.We extracted information from 16 studies published between 2019 and 2023 that described a total of 63 cases of antifungal‐resistant dermatophytosis caused by T. indotineae in Europe. Antifungal susceptibility testing (AFST) revealed a wide range of terbinafine minimum inhibitory concentrations (MICs), varying from 0.014 to ≥16 μg/mL. However, these values are hard to interpret due to variations among used methodologies as well as the lack of clinical breakpoints. In all cases included in this study, elevated terbinafine MICs were associated with mutations in the squalene epoxidase (SQLE) gene. Itraconazole was the most frequently used alternative to terbinafine in this study and complete remission of tinea lesions after treatment switch was shown. Nevertheless, relapse rates are concerningly high.We propose the implementation of surveillance programmes for a fast identification through sequencing of T. indotineae (and SQLE mutations) and standardization of procedures for AFST to facilitate the establishment of clinical breakpoints and enable guidance on the appropriate use of antifungals. [ABSTRACT FROM AUTHOR]

Background: There is a concerning rise in antifungal‐resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. Objectives: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. Methods: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18‐month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real‐time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). Results: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. Conclusion: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk. [ABSTRACT FROM AUTHOR]

Background: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. Objectives: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). Methods: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. Results: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard‐to‐treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. Conclusion: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness. [ABSTRACT FROM AUTHOR]

Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch's permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0–8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections. [ABSTRACT FROM AUTHOR]

Dermatophytic pseudomycetoma (DPM), which is a deeper dermal and/ or subcutaneous infection of dermatophytes, has been rarely reported in Domestic Korean Short Hair Cats. A 3-year-old, spayed female, domestic Korean Short Hair Cat presented with a history of crusts, nodules, and pruritus for 1 year. At the initial presentation, multifocal ulcerative nodules covered with yellowish grains were noted on her ventral thorax, abdomen, flank, and left hindlimb. Cytology of ulcerative nodules revealed degenerative neutrophils, macrophages, multinucleated giant cells, and hyphae. Histological examination of nodules revealed pyogranulomatous dermatitis with fungal plaques, and Microsporum canis and Staphylococcus aureus were identified in the culture. Therefore, the cat was diagnosed with DPM with secondary pyoderma. Oral itraconazole (10 mg/kg, once a day) was administered, but no significant improvement was observed. Therefore, intralesional (IL) injection of amphotericin B (0.6 mg/nodule) and oral administration of terbinafine (30 mg/kg, twice a day) were administered to the cat. With these medications, ulceration and the number and size of nodules decreased significantly, although large dome-shaped nodules remained. Skin lesions were treated with oral terbinafine and itraconazole administration for 5 months. However, after 6 months, recurrence of multifocal ulcerative nodules was observed, and the cat died 10 months after initial presentation. In this case, IL amphotericin B and oral terbinafine administration were partially effective in DPM treatment, suggesting that this may be an option for DPM treatment. Further studies to determine dose and frequency of IL amphotericin B in the management of DPM are warranted. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis is a prevalent superficial infection caused by filamentous fungi, primarily affecting the skin and/or its appendages. In recent years, there has been a notable increase in mycotic strains resistant to standard antifungal therapies, including Trichophyton indotineae, a dermatophyte of the Trichophyton mentagrophytes complex. This review aims to provide a comprehensive overview of the treatment options for T. indotineae, elucidating their effectiveness in managing this challenging mycotic infection. Methods: For this review, a search was conducted in the PubMed, Scopus, Web of Science, Embase, and Google Scholar databases, encompassing all published data until March 2024. English-language articles detailing therapy outcomes for patients confirmed to be affected by T. indotineae, identified through molecular analysis, were included. Results: Itraconazole was shown to be a good therapeutic choice, particularly when administered at a dosage of 200 mg/day for 1–12 weeks. Voriconazole was also demonstrated to be effective, while terbinafine exhibited a reduced response rate. Griseofulvin and fluconazole, on the other hand, were found to be ineffective. Although topical treatments were mostly ineffective when used alone, they showed promising results when used in combination with systemic therapy. Mutational status was associated with different profiles of treatment response, suggesting the need for a more tailored approach. Conclusions: When managing T. indotineae infections, it is necessary to optimize therapy to mitigate resistances and relapse. Combining in vitro antifungal susceptibility testing with mutational analysis could be a promising strategy in refining treatment selection. [ABSTRACT FROM AUTHOR]

Introduction: Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging–Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging. Methods: Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails (n = 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC90) of Trichophyton rubrum, the fold differences between the MIC90 and the antifungal concentrations in the nails (the multiplicity of the MIC90) were calculated overall and for the keratin-unbound fractions. Results: Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3 h following terbinafine treatment was 1414 μg/g of tissue (equivalent to 4.9 mM) compared with 780 μg/g (2.5 mM) following amorolfine treatment (not significantly different; p = 0.878). The median multiplicity of the MIC90 was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48; p = 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8; p = 0.002). Conclusion: In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC90 values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success. [ABSTRACT FROM AUTHOR]

Introduction: Tinea pedis is one of the most common skin conditions that often affects athletes, which is referred to by another name for the condition - Athlete's foot. It is a fungal infection that manifests itself with symptoms such as itching, redness, exfoliating skin and cracking of the epidermis. The foot skin infection can spread to the nails, so in this review we will discuss both conditions. Terbinafine is an allylamine derivative with antifungal activity. It can be applied both superficially and orally. It is used to treat fungal infections, including tinea pedis and onychomycosis. Aim of the study: The aim of this publication is to review the available literature to answer the question of whether terbinafine is an effective treatment for athlete's foot and onychomycosis. Methods: Review of specialised literature in the field of dermatology and PubMed and Google Scholar databases by searching with keywords such as athlete’s foot, tinea pedis, onychomycosis, terbinafine. Conclusion: Tinea pedis and often associated onychomycosis are a medical problem affecting a wide social group. Topical or systemic drugs can be used to treat the aforementioned conditions. Terbinafine, which is a drug belonging to the allylamines, is effective in the treatment of tinea pedis and onychomycosis and has a high safety profile. There are terbinafine products on the market in various forms, e.g. emulsions, creams, film-forming solution, pills, so it is therefore easy to choose a suitable and convenient treatment. The use of lasers such as CO2 fractional laser or Nd:YAG laser seems to be beneficial in the complementary treatment of onychomycosis with terbinafine.

The sensitivity of field cultures of fungal microbe Aspergillus niger to new synthetic analogs of natural antifungal antibiotics of the isocoumarin class was determined in comparison with antimycotic activity of known drugs. The minimal mycocidal concentration (MMCC) and minimal mycostatic concentration (MMSC) of the drugs were documented. The inhibitory effect (IE) was expressed as the ratio of the average colony diameter of experimental samples to the average colony diameter of control samples. From the results presented in the present work, it follows that the investigated field cultures of Aspergillus niger are most sensitive to antimycotic drugs belonging to N-methylnaphthylmethylamine derivatives and polyene antimycotics — terbinafine (MMSC = 0–2 µg/cm3) and nystatin (MMSC = 4–8 µg/cm3, IE-1 = 1.69, IE-K2 = 1.51), which have a pronounced mycocidal effect. Other studied preparations, including synthesized analogues of natural isocoumarins, showed only mycostatic effect on cultures of fungal microbe Aspergillus niger: fluconazole — MMSC = more than 64 µg/cm3, IE-K1 = 3.38, IE-K2 = 2.52; griseofulvin — MMSC = more than 64 µg/cm3, IE-K1 = 1.79, IE-K2 = 1.53; 3-(3-oxobutyl)-isocoumarin — MMSC = more than 64 µg/cm3, IE-K1 = 1.27, IE-K2 = 1.07; 7-fluoro-3-(oxobutyl)-1-N-isochromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.28, IE-K2 = 1.03; (E)-3-(3-oxobutyl-1-en-1-yl)-1-N-isochromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.12, IE-K2 = 1.06; 3-(3,3-difluorobutyl)-1-N-iso-chromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.34, IE-K2 = 1.25.

Introduction: Although the diagnosis of tinea capitis is mainly microbiological, the risk of evolution towards cicatricial alopecia in the most severe cases requires empirical treatment based on physical examination and complementary examinations. Methods: Two patients were evaluated by physical examination, cutaneous ultrasound and microbiological examination. Results: Ultrasound showed follicular widening and increased vascularization in Doppler mode. In one of them, the finding of severe inflammatory activity led to the indication of oral corticotherapy. Discussion: Cutaneous ultrasound could play a role not only in supporting the clinical diagnosis but that it may even guide the indication of treatment in the presence of severe inflammation that sometimes may not manifest itself clinically. Conclusion: Cutaneous ultrasound may constitute an additional test of considerable usefulness in the diagnosis and evaluation of inflammatory activity in cases such as the ones presented, fast, non‐invasive and of high accessibility. [ABSTRACT FROM AUTHOR]

The article discusses a case report on the successful treatment of tinea capitis caused by Trichophyton rubrum in a patient with autoimmune chronic hepatitis using daylight photodynamic therapy with BF‐200 ALA combined with topical terbinafine. The standard treatment for tinea capitis involves systemic antifungal medications, but in this case, systemic antifungals were contraindicated due to the patient's liver condition. The combination of photodynamic therapy with oral antifungal medications showed improved treatment efficacy, leading to complete resolution of the infection in the patient. The treatment was well-tolerated, and the patient remained in remission 15 months after the therapy. [Extracted from the article]

The article discusses a case of terbinafine-induced subacute cutaneous lupus erythematosus (SCLE) in a 71-year-old woman with a history of Sjögren syndrome. Despite traditional treatments failing to alleviate her symptoms, the patient experienced rapid resolution of her condition within 48 hours of upadacitinib treatment. Upadacitinib, a JAK1 inhibitor, has shown promise in managing various autoimmune conditions, including cutaneous lupus, and further research into its efficacy in drug-induced SCLE is warranted. The case highlights the potential of upadacitinib in treating refractory cases of lupus-related cutaneous eruptions. [Extracted from the article]

This article discusses a case of hydroxychloroquine-induced acute generalized exanthematous pustulosis (AGEP) that was successfully treated with secukinumab, an IL-17 antagonist. AGEP is a rare severe cutaneous adverse reaction characterized by the acute onset of widespread pustules on an erythematous base. Hydroxychloroquine is a commonly used antimalarial drug that can cause AGEP as a skin adverse reaction. The patient in this case experienced worsening symptoms despite treatment with systemic corticosteroids and cyclosporine, but showed significant improvement after receiving secukinumab. This case suggests that IL-17 antagonists could be a promising therapeutic option for refractory cases of AGEP. [Extracted from the article]

In recent decades, many fungi have emerged as major causes of disease in marine mammals. This study reports on the detection of filamentous fungi in the subcutaneous tissue and wound surface on the tail fin of a managed bottlenose dolphin (Tursiops truncatus) emaciated due to severe digestive problems. Immunosuppression by chronic diseases and starvation decreased resistance against opportunistic infections. Sequencing analysis revealed that the fungi on the wound surface were Fusarium oxysporum, and antifungal susceptibility testing was performed. In the subcutaneous tissue, dematiaceous fungi were identified using histopathological examination. Combination antifungal treatment with voriconazole and terbinafine and surgical resection were performed, in addition to daily debridement with polyaminopropyl biguanide (PHMB) and betaine. Hematological examination revealed a reduction in inflammatory markers after antifungal treatment and surgical resection of necrotic tissue on the edge of the tail fin. The co-administration of synergistic agents voriconazole and terbinafine, in conjunction with surgical debridement, successfully eliminated pheohyphomycosis and fusariomycosis in the bottlenose dolphin. Wound healing was achieved using systematic antifungals and daily debridement with PHMB and betaine. This is the first report of successful treatment of pheohyphomycosis and fusariomycosis in a bottlenose dolphin using voriconazole and terbinafine combination therapy and surgical resection.

Background: While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods: We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. Results: Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. Conclusions: Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment. [ABSTRACT FROM AUTHOR]

The unique properties of calcium oxide (CaO) and zinc oxide (ZnO) at the nanoscale have attracted the interest of scientists as promising electrically conductive substances for sensing purposes. The content of terbinafine hydrochloride (TRF) in pharmaceutical tablets was determined using a novel coated, wire‐functionalized CaO/ZnO nanocomposite membrane sensor biogenically produced from Lavandula spica extract. Sodium tetraphenylborate was used to prepare the active material (TRF‐TBP). The newly modified sensor gave excellent potentiometric sensitivity with the least squares regression equation EmV=(−58.88X±0.3)+log [TRF]+549.78 and covered a wide linear range (5.0×10−9–1.0×10−2 mol/L) of TRF samples. In contrast, the standard TRF‐TBP sensor wasn't as sensitive when (2.5×10−6–1.0×10−2 mol/L). TRF solutions with regression equation of (−55.728X±0.7)+log [TRF]+396.64. The appropriate pH range was 3–6. The principles of analytical methodology were applied to investigate the validity and suitability of the proposed technique. The proposed sensors were found to be suitable and efficient for the detection of TRF on tablets. [ABSTRACT FROM AUTHOR]

Background: Onychomycosis is a chronic fungal infection of the nail unit. The therapeutic options include oral antifungals as terbinafine, pulse itraconazole, fluconazole and voriconazole. Various laser systems have been tried for resistant cases to improve the results of treatment as carbon dioxide (CO2) and Nd:YAG lasers. Objective: Compare between two treatment methods; combined therapy of fractional CO2 laser (FCO2L) plus topical tioconazole 28% nail solution versus topical tioconazole 28% nail solution alone in the same patient with fingernails onychomycosis. Methods: This was prospective comparative interventional study conducted on 20 patients with two or more affected fingernails. The degree of affection of the studied nails was assessed clinically by onychomycosis severity index (OSI) and was confirmed by KOH and mycological culture. The studied nails were categorized into two corresponding groups; group (A), fingernails were treated with combined therapy in the form of 4-6 fractional CO2 laser sessions four weeks apart plus topical tioconazole 28% twice daily for six months, group (B), fingernails were treated with topical tioconazole 28% alone twice daily for six months. Results: A high statistically significant improvement was reported among patients treated with combined therapy than those who treated with antifungal only. The CO2 laser plus topical tioconazole solution yielded significantly higher percentage of improvement for onychomycosis. Conclusion: Both combined therapy and local therapy reported safe and promising outcomes. However combined therapy was associated with better improvement and local therapy was associated with minimal adverse events. [ABSTRACT FROM AUTHOR]

Background: Dermatomycoses count to the most frequent dermatoses in Cambodia. Objectives: The aim of this survey was to investigate the occurrence of dermatophytes in this Southeast Asian country. Methods: From June 2017 to July 2018, skin scrapings were taken from 67 patients with superficial dermatophytosis for mycological diagnostics. Identification of dermatophytes was confirmed by sequencing of the 'internal transcribed spacer'—(ITS) region of the rDNA, and the gene of the Translation Elongation Factor (TEF)‐1α. Results: Patients were suffering from tinea corporis and tinea inguinalis/cruris 42/67 (63%), tinea capitis/faciei 14/67 (21%), tinea corporis/capitis/faciei 6/67 (9%), tinea manuum/pedis 2/67 (3%), tinea pedis 2/67 (3%) and tinea manuum 1/67 (1%). Both, by culture and/or PCR, a dermatophyte was detected in 52 (78%) out of 67 samples. Culture positive were 42 (81%) of 52, PCR positive were 50 (96%). The following dermatophytes were found: Trichophyton (T.) rubrum, 36/52 strains (69%, 29 by culture), T. mentagrophytes/T. interdigitale (TM/TI) 9/52 (17%, six by culture) and Microsporum (M.) canis 5/52 strains (10%, by culture). One strain of Nannizzia (N.) incurvata 1/52 (2%) and N. nana 1/52 (2%) was isolated. Based on sequencing, we demonstrated that two T. mentagrophytes strains out of the nine TM/TI represented the new ITS genotype XXV Cambodia. We found one T. mentagrophytes strain genotype VIII (now, reclassified as T. indotineae). This isolate was terbinafine resistant, and it exhibited the amino acid substitution Phe397Leu in the squalene epoxidase. Three strains of T. interdigitale genotype II* were isolated. Conclusion: This is the first survey on epidemiology of dermatophytes in Cambodia. Currently, T. rubrum represents the most frequent species in Cambodia. One Indian strain genotype VIII T. mentagrophytes was found. A highlight was the first description of the new T. mentagrophytes genotype XXV Cambodia. [ABSTRACT FROM AUTHOR]

The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole. Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered. [ABSTRACT FROM AUTHOR]

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains. [ABSTRACT FROM AUTHOR]

Aim/Background: According to estimates, about a billion people in the world have fungal infections of the skin, nails, and hair. Skin disorders are a significant contributor to disability, deformity, and misery among people. In the present study, a versatile vesicular delivery of terbinafine hydrochloride through the dermal route in a biocompatible platform consisting of glycerine, phospholipids, and cholesterol is proposed for the treatment of mycoses. Materials and Methods: The glycerosomes of terbinafine hydrochloride were formulated by thin film hydration technique using central composite design to explore the composition effects on the formation of nanosized stable glycerosomes and drug loading. The optimized formulation was evaluated for deformability, antifungal activity, compatibility by FTIR, surface morphology, in vitro and ex vivo drug diffusion, skin irritation, histopathology, and cytotoxicity studies on HaCaT cell lines. Results: Numerical optimization of the design revealed that the particle size and entrapment efficiency of the drug were remarkably affected by the composition. Surface imaging by TEM revealed the formation of well-defined vesicles with no aggregation. The elasticity of the vesicles was established by determining their deformability index. The in vitro and ex vivo drug release study revealed better permeation of the drug compared to the marketed formulation. The histopathology and cytotoxicity study conceded the suitability of the glycerosomal carrier system for the transdermal delivery of terbinafine hydrochloride. Conclusion: Hence it can be concluded that the glycerosomes of terbinafine hydrochloride possess a potential formulation approach for treating dermal infection. [ABSTRACT FROM AUTHOR]

Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid–Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of endogenous Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim. Case report: A 57-year-old man developed disseminated Lomentospora prolificans with right endophthalmitis on the background of immunosuppression following lung transplantation for interstitial lung disease. He was treated with early vitrectomy, intravitreal voriconazole, and systemic Olorofim, voriconazole and terbinafine. His symptoms improved and remained stable in the right eye. Eight weeks later the patient represented with Lomentopora prolificans endophthalmitis in the left eye when systemic voriconazole and terbinafine treatment were withdrawn. Despite aggressive treatment he ultimately succumbed due to vascular complications of extensive disseminated disease. Conclusion: We report a rare case of disseminated Lomentosporosis with panophthalmitis in an immunocompromised host with prolonged survival on systemic Olorofim, voriconazole and terbinafine in conjunction with pars plana vitrectomy and intravitreal voriconazole. Early suspicion of an opportunistic fungal infection is critical, as managing disseminated disease is often unsuccessful. Despite presumed inherent resistance, intravitreal and systemic voriconazole appeared to limit disease progression in the right eye. The potential synergistic effects of combined antifungal therapy with orotomides warrant further investigation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum ( 13.8% i n 4 9 s amples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development. [ABSTRACT FROM AUTHOR]

Background: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. Methods: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. Results: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. Conclusion: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological data. This retrospective study concerned all patients with CBM proven by at least one paraclinical examination and diagnosed in French Guiana between 1950 and 2023. In total, 23 patients were included, mostly males (87%) of Creole origin, living in the coastal region (87%) and involved in outdoor occupations (74%). Lesions were mostly observed on the lower limbs (78.3%), with a median time to diagnosis of four years. Laboratory tests included positive direct microscopic examinations (78.3%) and mycological cultures (69.6%), identifying 14 cases of Fonsecaea pedrosoi and one case of Exophiala janselmei. Various treatments were employed, including antifungals, surgery and combinations of both. In conclusion, CBM in French Guiana involves a different population than other subcutaneous mycoses such as Lobomycosis or Paracoccidioidomycosis, mostly found in the forest hinterland. Surgery should be recommended for recent and limited lesions. Itraconazole and terbinafine should systematically be proposed, either in monotherapy or in combination with surgery or cryotherapy. [ABSTRACT FROM AUTHOR]

Background: Tinea incognito presents with atypical, widespread, and recurrent lesions. Dermoscopy can aid its rapid diagnosis. Aim and Objectives: This study aimed at assessing dermoscopic features and response to treatment in patients with tinea incognito. Materials and Methods: An evaluation of 62 patients with tinea of glabrous skin (Group A (cases)—31 steroid modified and Group B (controls)—31 treatment naïve) was done. Clinical, dermoscopic, and mycological evaluations were done for both groups at baseline, 2, and 4 weeks of terbinafine therapy. Clinical severity (Clinical Assessment Severity Score (CASS) and Visual Analogue Scale (VAS)) and frequency of various dermoscopic changes were compared at 0 and 4 weeks between cases and controls, using unpaired Student's t-test, Mann–Whitney U-test, and Wilcoxon signed-rank test. Results: Baseline dermoscopic features for both groups were significantly different with respect to frequency of broken hair, bent hair, micropustules and Morse code hair. Earliest feature to resolve with treatment was micropustules at 2 weeks. Significant reduction in frequency of morphologically altered hair was evident at 4 weeks. Telangiectasia, dotted vessels, I-hair, and broken hair persisted for a longer period of time. Terbinafine for 4 weeks was an effective treatment, producing complete cure in 73% of cases and 93% of controls. Persistent dermoscopic changes at 2 weeks were found to be associated with treatment failure at 4 weeks, highlighting the role of dermoscopy in identifying patients requiring prolonged treatment. Conclusions: Dermoscopy can be used as a diagnostic and monitoring tool for tinea of glabrous skin. [ABSTRACT FROM AUTHOR]

Background: Onychomycoses are difficult‐to‐treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. Objectives: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. Methods: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96‐well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. Results: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. Conclusions: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non‐dermatophyte fungus such as S. brevicaulis. [ABSTRACT FROM AUTHOR]

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended. [ABSTRACT FROM AUTHOR]

Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium. [ABSTRACT FROM AUTHOR]

This article presents the findings of a clinical trial that compared the effectiveness of two antifungal creams, ciclopirox olamine and terbinafine hydrochloride, in treating dermatophytosis. The study involved 60 patients with tinea corporis, tinea cruris, or tinea faciei, who were divided into three groups and treated with different creams for 6 weeks. The results showed that both creams were effective in treating the condition, but the combination therapy of both creams had a better response and lower relapse rate. The study acknowledges its limitations, such as a small sample size and short follow-up period, but concludes that the combination therapy is effective with no significant side effects. [Extracted from the article]

ABSTRACT Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N′-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.IMPORTANCEThis paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

We use here two genomic screens in an attempt to understand the mode of action and resistance mechanism of terbinafine, an antifungal contemplated as a potential drug against the parasite Leishmania. One screen consisted in in vitro drug evolution where 5 independent mutants were selected step-by-step for terbinafine resistance. Sequencing of the genome of the 5 mutants revealed no single nucleotide polymorphisms related to the resistance phenotype. However, the ERG1 gene was found amplified as part of a linear amplicon, and transfection of ERG1 fully recapitulated the terbinafine resistance phenotype of the mutants. The second screen, Cos-seq, consisted in selecting a gene overexpression library with terbinafine followed by the sequencing of the enriched cosmids. This screen identified two cosmids derived from loci on chromosomes 13 and 29 encoding the squalene monooxygenase (ERG1) and the C8 sterol isomerase (ERG2), respectively. Transfection of the ERG1-cosmid, but not the ERG2-cosmid, produced resistance to terbinafine. Our screens suggest that ERG1 is the main, if not only, target for terbinafine in Leishmania and amplification of its gene is the main resistance mechanism.

This article discusses the emergence of a novel and highly infectious fungus called Trichophyton indotineae, which is causing an epidemic of drug-resistant tinea infections. The fungus has spread globally, including to Australia, and is often resistant to terbinafine, the recommended antifungal treatment. The article emphasizes the importance of accurate laboratory diagnosis through culture and sequencing of the fungal DNA, as well as the need for surveillance studies to understand the frequency and treatment outcomes of T. indotineae infections in Australia. Clinicians and laboratories are advised to be aware of this infection and to avoid prescribing topical corticosteroid treatment. [Extracted from the article]

Phytoene is an uncommon linear carotene within the carotenoid group as it is colorless due to its short chromophore. Recent research constitutes a relatively new area which has emerged from phytoene’s importance as a major dietary carotenoid promoting health and appearance. Its resources point to the potential of biotechnological production systems. Our work has been designed to study the efficacy of two colored carotenoid biosynthesis inhibitors, diphenylamine and 2-methyl imidazole, and one sterol biosynthesis inhibitor, terbinafine, to modify the metabolic flux in mated cultures of Blakeslea trispora to achieve maximum phytoene production. Bioprocess kinetics optimized by response surface methodology and monitored by high-performance liquid chromatography revealed maximum phytoene content (5.02 mg/g dry biomass) and yield (203.91 mg/L culture medium) comparable or even higher than those reported for other potent phytoene microbial producers. The in vivo antioxidant activity of phytoene-rich carotenoid extract from fungal cells was also considered and discussed.

Background: Terbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited. Objectives: This research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms. Patients/Methods: A total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines. Results: While no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L−1) but low MICs to the other seven antifungals tested except for fluconazole. Conclusions: This study highlights the emergence of terbinafine‐resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change. [ABSTRACT FROM AUTHOR]

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 µg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans. [ABSTRACT FROM AUTHOR]

The purpose of this review is to consolidate and summarize laser-assisted drug delivery (LADD) for nail diseases, particularly onychomycosis and psoriasis. A PubMed search was conducted in June 2023 using search terms (1) "laser assisted drug delivery" AND "nail," (2) "laser" AND "nail," and (3) "nail disorder" AND "laser treatment." References of papers were also reviewed, yielding 15 papers for this review. Fractional ablative CO2 laser (FACL) and Er:YAG laser can be used for LADD of topical medications such as amorolfine, terbinafine, and tioconazole to treat onychomycosis. A fungal culture should be performed to determine the type of dermatophyte, which will help determine which topical will be most effective. Laser settings varied between studies, but overall LADD tended to be more effective than topical treatments alone. Laser-assisted photodynamic therapy (PDT) was also found to be effective in treating onychomycosis. For psoriatic nails, LADD was used to deliver calcipotriol-betamethasone dipropionate foam, tazarotene, triamcinolone, or methotrexate into the nail. Again, LADD was found to be significantly more effective than topical treatment alone. FACL was the only laser noted for use for LADD in both diseases. Laser-assisted drug delivery for nail disease is a newer approach for onychomycosis and nail psoriasis with several benefits and drawbacks. Dermatologists should discuss the option of LADD with their patients who have recalcitrant onychomycosis or nail psoriasis. [ABSTRACT FROM AUTHOR]