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This study explores the effectiveness of various antifungal drugs in treating sporotrichosis caused by Sporothrix schenckii, especially in non-wild-type (non-WT) strains. The drugs tested include enilconazole (ENIL), isavuconazole (ISA), posaconazole (POS), terbinafine (TER), and itraconazole (ITC). The study involved in vitro and in vivo tests on 10 WT isolates and eight ITC non-WT isolates. Two isolates were assessed using time-kill assays, checkerboard assays, and Galleria mellonella infection models. In vitro studies have shown that all of these drugs were more effective than or equal to ITC against WT and non-WT isolates. No ITC resistance was observed with other azoles. All drugs inhibited fungal growth of WT and non-WT strains within 24 h at all incubations. ENIL and TER showed fungicidal effect against types at over 2x minimum inhibitory concentrations with no regrowth. POS was fungicidal against WT at high concentrations but not against non-WT. ISA was only fungicidal for non-WT. ITC did not exhibit any fungicidal activity. In checkerboard experiments, the combination of POS or ISA with TER showed enhanced activity against WT and non-WT strains, surpassing the combination of ITC with TER. In vivo model experiments demonstrated significantly reduced mortality rates with ENIL, POS, and TER against WT and with ENIL, ISA, POS, and TER against non-WT. The study concludes that monotherapy with ENIL, ISA, POS, and TER, and combinations of POS/TER or ISA/TER, show promise as effective antifungal treatments against S. schenckii, including ITC-non-WT isolates. [ABSTRACT FROM AUTHOR]

The development of resistance to traditional antifungal therapies has necessitated the exploration of alternative treatment strategies to effectively manage fungal infections, particularly those induced by Candida albicans (C. albicans). This research investigates the possibility of integrating silver nanoparticles (AgNPs) with Terbinafine to improve antifungal effectiveness. Terbinafine, while potent, faces challenges with specific fungal strains, highlighting the need for strategies to enhance its treatment efficacy. Silver nanoparticles were produced through a light-activated, gelatin-based method, resulting in particle sizes ranging from 56.8 nm to 66.2 nm, confirmed by dynamic light scattering and scanning electron microscopy. Stability studies indicated that AgNPs produced with 30 mg of silver nitrate (AgNO₃) exhibited the greatest stability over 60 days across different temperature conditions. The analysis through UV-visible spectrophotometry revealed a notable shift in the absorption spectra as AgNO₃ concentrations increased, which was associated with a strengthening of plasmon resonance. The effectiveness of the AgNPs and Terbinafine combination was assessed against three strains of C. albicans (ATCC 10231, ATCC 90028, and ATCC 18804). Terbinafine demonstrated strong antifungal properties with minimum inhibitory concentrations (MIC) values ranging from 2–4 µg/mL, whereas AgNPs on their own displayed moderate effectiveness. The integrated formulation notably enhanced effectiveness, especially against strain ATCC 90028, revealing a synergistic effect (FIFi = 0.369). These results were complemented by the findings of the time-to-kill assay, where the same strain showed a 3.2 log₁₀ CFU/mL decrease in viable cell count. The process by which AgNPs boost activity entails the disruption of the fungal cell membrane and its internal components, probably as a result of silver ion release and the generation of free radicals. The results indicate that the combination of Terbinafine and AgNPs may act as a powerful alternative for addressing resistant fungal infections, presenting an encouraging direction for future antifungal treatments. [ABSTRACT FROM AUTHOR]

Background: The widespread occurrence of chronic and recurrent dermatophytosis has significantly affected the quality of life for patients in India and beyond. Identifying the causative dermatophytes and understanding their antifungal susceptibility can aid clinicians in tailoring effective antifungal therapies. Materials and Methods: Patients with chronic and recurrent dermatophytosis were enrolled, and conventional fungal cultures were conducted on skin scrapings. Identified isolates underwent antifungal susceptibility testing using the Clinical and Laboratory Standards Institute broth microdilution method (CLSI M38-A2) for common systemic antifungals, determining the minimum inhibitory concentration (MIC) range and calculating MIC 50 and MIC 90. Results: Sixty samples were tested. Tinea corporis was the most common presentation (66.6%). Trichophyton mentagrophyte species complex was the prevalent species (45, 75%), followed by Trichophyton rubrum (7, 11.7%). In Trichophyton mentagrophytes species complex, MIC range was 8-64 μg/mL for fluconazole, 0.06-0.25 μg/mL for terbinafine, and 0.125-0.5 μg/mL for griseofulvin. For Trichophyton rubrum , the MIC range was 8-64 μg/mL for fluconazole, 0.06-0.25 μg/mL for terbinafine, and 0.125-0.5 μg/mL for griseofulvin. For all species, itraconazole MIC was ≤0.125 μg/mL. Hence, itraconazole and terbinafine had the best MIC range against tested isolates in our study. Limitations: Absence of genotyping of isolate and not compared the results with studies where sequence-based identification to species level was done. Conclusion: In vitro , resistance to itraconazole for any of the four isolated agents was not seen. Terbinafine resistance appears to be an uncommon occurrence in South India. In vitro susceptibility tests shall be regularly done to design the epidemiological cutoff values. [ABSTRACT FROM AUTHOR]

The article in the Journal of Cutaneous Pathology discusses a case of Acantholytic PRIDE syndrome in a 63-year-old male with chronic myeloid leukemia who developed pus-filled lesions on his limbs after starting imatinib therapy. The patient was treated with topical clobetasol ointment, levocetirizine tablets, and moisturizers, showing improvement at a 3-month follow-up. The syndrome is linked to tyrosine kinase inhibitors like EGFRIs and presents with various cutaneous manifestations, requiring differentiation from other conditions like Grover disease and AGEP. The study highlights the need for further research to understand the exact mechanisms behind acantholysis in PRIDE syndrome. [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. [ABSTRACT FROM AUTHOR]

Background: Pityriasis versicolor is a prevalent superficial mycosis caused by saprophytic yeasts of the Malassezia genus. It primarily affects adolescents and young adults, presenting as hypo- or hyperpigmented macules on the skin, commonly located on the trunk and upper arms. While various topical and systemic antifungal treatments are available, high relapse rates remain a significant clinical challenge. The condition often leads to psychological distress due to visible lesions on the skin surface. Aim of the study: Given its high prevalence (reaching up to 50% in some tropical regions) and its psychosocial implications, pityriasis versicolor remains a critical dermatological concern. This study aims to synthesize current medical knowledge about the condition, focusing on the efficacy, indications, and limitations of available treatment options, especially in addressing recurrent cases. State of knowledge: Pityriasis versicolor is well-characterized in terms of its etiology and clinical manifestations. Numerous therapeutic interventions have been investigated, ranging from topical agents like azoles or terbinafine to systemic treatments such as itraconazole and fluconazole. Despite these advancements, a universally accepted gold standard for treatment remains undefined, and patient adherence often is a barrier to successful outcomes. Conclusion: Despite significant progress in understanding and managing pityriasis versicolor, further research is essential. Future efforts should aim to optimize treatment efficacy, reduce relapse rates, and minimize adverse effects. Randomized controlled trials with larger and more diverse populations are particularly needed to establish standardized protocols and explore innovative therapies, including prophylactic measures and targeted treatments. [ABSTRACT FROM AUTHOR]

Background: Terbinafine resistance in dermatophytes is an increasing problem worldwide. Several outbreaks of terbinafine‐resistant dermatophytosis are currently occurring in India and surrounding countries, and these recent years, European countries have also been affected by this issue. Currently, antifungal susceptibility testing of dermatophytes is not routinely performed in clinical laboratories. Objectives: Given the current situation and associated public health concerns, there is an urgent need for accurate and rapid detection of terbinafine resistance in laboratories. Therefore, we evaluated different methods currently available for the detection of terbinafine resistance in dermatophytes. Methods: Twenty‐eight strains previously identified as T. indotineae/mentagrophytes/interdigitale were concurrently characterised using terbinafine gradient strips (HiMedia), EUCAST E.Def 11.0 microdilution, the DermaGenius resistance PCR assay (PathoNostics), and SQLE sequencing. These four methods were compared to terbinafine resistance characterisation obtained by whole genome sequencing (WGS). Results: All four evaluated methods were able to detect terbinafine resistant strains either by showing high MICs (> 0.125 μg/mL) or by detecting SQLE substitutions. Conclusions: The gradient strips, despite questionable essential agreement with EUCAST E.Def 11.0, can be an easy, fast and cheap method to screen terbinafine resistance among dermatophytes in clinical laboratories. The DermaGenius resistance PCR assay enables rapid detection of the most common substitutions in SQLE associated with terbinafine resistance. However, its inability to precisely determine specific substitutions on SQLE or identify new ones may pose a problem in the future. These limitations can be addressed by using SQLE sequencing or whole genome sequencing (WGS). [ABSTRACT FROM AUTHOR]

Background/objectives: Topically applied antifungal agents can induce adverse effects, such as pain and irritation. The transient receptor potential (TRP) channels—TRPA1 and TRPV1—mainly expressed in sensory neurons, act as sensors for detecting irritants. This study aims to evaluate the involvement of nociceptive channels in topical antifungal‐induced pain and irritation. We tested nine topical antifungals belonging five classes: isoconazole, econazole, miconazole, clotrimazole, and ketoconazole as imidazoles; liranaftate as a thiocarbamate; terbinafine as an allylamine; amorolfine as a morpholine; and butenafine as a benzylamine. Methods: Intracellular calcium concentrations ([Ca2+]i) and membrane currents in response to antifungals were measured to estimate channel activity using heterologously expressing cells and isolated mouse sensory neurons. Results: In mouse TRPA1‐expressing cells, all the tested drugs induced an increase in [Ca2+]i, which was abrogated or reduced by a TRPA1 blocker. Although many drugs evoked the TRPA1‐nonspecific [Ca2+]i response at high concentrations, responses to clotrimazole, ketoconazole, and liranaftate were TRPA1 specific and elicited current responses in TRPA1‐expressing cells. In mouse TRPV1‐expressing cells, clotrimazole and ketoconazole elicited [Ca2+]i and current responses. In mouse sensory neurons, liranaftate‐induced increase in [Ca2+]i was abrogated by a TRPA1 blocker and Trpa1 deletion. Responses to ketoconazole were inhibited by TRPA1 and TRPV1 blockers and by the genetic deletion of either channel. Conclusion: These results suggest that topical antifungal‐induced pain and irritation are attributable to the activation of nociceptive TRPA1 and/or TRPV1 channel/s. Consequently, caution should be exercised in the use of topical antifungals with symptoms of pain. [ABSTRACT FROM AUTHOR]

The goal of this study is to evaluate the antifungal activity of terbinafine in its nano form against yeast organisms in vitro and compare its effectiveness to the normal form of terbinafine. Thirty isolated yeast organisms from Thumbay Labs were included in the study. Terbinafine was serially diluted to concentrations of 50 mg, 25 mg, 12 mg, and 6 mg for both the nano and normal forms. After preparing the serial dilutions, fungal suspensions were exposed to these dilutions for 7 minutes. The suspensions were then cultured on Sabouraud dextrose agar and incubated at 37°C overnight. Growth was measured using a colony count. The results for the normal form of terbinafine revealed growth at all concentrations, with varying colony counts with a highest growth was observed at the 6 mg concentration. In contrast, the nano form of terbinafine exhibited distinct development patterns. At the 50 mg concentration, seven samples showed no growth; at the 25 mg concentration, two samples showed no growth; and the remaining samples exhibited limited growth compared to the normal form. According to the results of this study, there were significant differences in the number of colonies between the two forms of terbinafine, with the nano form demonstrating greater efficacy. The most potent antifungal response was observed at the 50 mg concentration of nano terbinafine, which inhibited yeast growth in several samples. In conclusion, terbinafine nanoemulsions are more effective than the normal form against Candida. [ABSTRACT FROM AUTHOR]

Introduction: Griseofulvin, discovered in 1939 and commercially available since 1959, was the first oral antifungal agent effective against dermatophytosis, particularly tinea capitis. Although it was eventually superseded by azole antifungals due to its long treatment duration and reliance on keratopoiesis, griseofulvin remains notable for its effectiveness and safety in treating tinea capitis, especially when caused by Microsporum canis. However, due to a decline in cases and commercial unavailability, alternative treatments are now required. Areas Covered: The following topics regarding to other treatments were discussed: (I) The efficacy of alternative antifungal agents such as terbinafine, itraconazole, and fluconazole, in the treatment of tinea capitis. (II) The use and role of topical therapies. (III) Experience in the management of tinea capitis. Expert Opinion: The usefulness of oral terbinafine as a replacement for griseofulvin in the treatment of tinea capitis and why it is the preferred drug in elderly patients was discussed. Challenges with Microsporum spp. and the use of fluconazole in pediatric patients were also analyzed. Support for the use of topical treatment as an adjunctive treatment for tinea capitis was highlighted. [ABSTRACT FROM AUTHOR]

Abstract Exophiala dermatitidis (E. dermatitidis), which causes skin or respiratory disease, is occasionally fatal in immunocompromised patients. Here, we report the unique antifungal potency of terbinafine (TRB), which targets squalene epoxidase, against E. dermatitidis (SQLEED) using various in vitro approaches. The versatile antifungal activities, including fungicidal activity, biofilm formation inhibition, biofilm eradication activity, and the combination effect of TRB, posaconazole (PSC), and amphotericin B (AmB) with great antifungal potency against E. dermatitidis were evaluated using crystal violet and cell viability assay. TRB formed an H-bond through Y102 in SQLEED in the binding model. E. dermatitidis hyphae elongated and attached to a cell scaffold, forming a membrane-like biofilm. TRB and PSC showed more potent antibiofilm activities than AmB, and exhibited post-antifungal effects without incubation against E. dermatitidis conidia, reducing growth at lower concentrations. In contrast, AmB exhibited strong dose- and time-dependent killing and biofilm-eradication activities. The combination of TRB and PSC was more effective than that of TRB and AmB or PSC and AmB. Although the tissue migration of TRB must be considered, these data suggest that TRB and PSC may be useful agents and a potent combination in severely immunocompromised patients with refractory and systemic E. dermatitidis infection.

Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Background Dermatophytes are the most common superficial fungal infections worldwide and are treated with prescribed regimens of terbinafine and itraconazole, or with weekly doses of fluconazole. Dermatologists are increasingly encountering treatment failures, and experts suggest that standard treatment regimens are not applicable anymore. We planned an open-label study to evaluate the results of fluconazole 150 mg daily for 8 weeks in patients with tinea cruris and tinea corporis. Methods Patients were enrolled from the La’Mer Clinic, Mumbai, India. We included adult subjects with uncomplicated dermatophytosis confirmed by microscopic examination of skin scrapings. Pregnancy, poor renal function, and recent exposure to anti-fungal therapy were exclusion criteria. Patients were reviewed on days 14, 28 and 56. The treating doctor scored the severity of erythema, scaling, and pruritus on a four-point scale: absent, mild, moderate, and severe. Of 107 subjects screened, 100 were finally included in the study. Eleven were lost to follow up and one subject withdrew consent. Results The site of disease was body alone in 29, groin alone in 7, and both body and groin in 64 cases. At 5 weeks, 98%, 100%, and 97% of patients had no scaling, erythema, and pruritus, respectively. Skin scrapings showed 100% mycological cure. In one patient the alanine transaminase level rose from 54.9 to 100.2 U/L, and qualified as a grade 1 adverse event not requiring intervention. No other significant adverse events were noted. Conclusions Our results suggest that fluconazole 150 mg daily for eight weeks effectively treats dermatophytosis. This regimen is safe and well-tolerated even in patients with co-morbidities. Fluconazole is about eight times less expensive than itraconazole or terbinafine and may be the preferred therapy. Registration The trial was registered with Clinical Trials Registry, India (Registration number CTRI/2020/06/026110) on 24 June 2020. FDC Company, India, provided financial support for the study.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adherence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity being mediated by the production of reactive oxygen species. This study investigates the in vitro effect of applying blue light (448 nm) or red light (645 nm), alone or together with terbinafine, on the viability of human keratinocytes and the production of reactive oxygen species. The combination of terbinafine and blue light significantly increases ROS production and caspase-3 expression, while red light together with terbinafine increases catalase, superoxide dismutase (SOD) and PPARγ expression, which reduces the amount of ROS in the cultures. The effect of both treatments could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity and shorten their duration. [ABSTRACT FROM AUTHOR]

Trichophyton (T.) mentagrophytes ITS genotype VIII, also known as Trichophyton indotineae, is a new species of the T. mentagrophytes/T. interdigitale complex and its first records, albeit under a different species name, are from the Indian subcontinent, Middle Eastern Asia, and West Asia. T. mentagrophytes genotype VIII (T. indotineae) has spread globally and has now been documented in over 30 countries. The aim of this study was to investigate the occurrence and proportion of terbinafine- and itraconazole-resistant isolates of T. mentagrophytes ITS genotype VIII (T. indotineae) in Bangladesh. This was part of an official collaborative project between IADVL (Indian Association of Dermatologists, Venereologists, and Leprologists) and Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. Over a period of 6 months, ninety-nine patients of chronic recalcitrant tinea corporis were recruited from BSMMU hospital. Species identification was performed by fungal culture and morphological observation of the upper and lower surfaces of fungal colonies, as well as by using fluorescent microscopy. In addition, a PCR (polymerase chain reaction)-ELISA was performed to group the patients into those with the T. mentagrophytes/T. interdigitale complex. The internal transcribed spacer (ITS) gene was sequenced. Samples were tested for resistance to terbinafine and itraconazole by mutational analyses of the squalene epoxidase (SQLE) and the ergosterol 11B (ERG11B) genes. A total of 79/99 samples showed a positive culture. In 76 of these isolates, T. mentagrophytes ITS genotype VIII (T. indotineae) could be reliably identified both by culture and molecular testing. Resistance testing revealed terbinafine resistance in 49 and itraconazole resistance in 21 patients. Among these, 11 patients were resistant to both the antifungal agents. Mutations L393S, L393F, F397L, and F397I of the SQLE gene were associated with terbinafine resistance. Resistance to itraconazole could not be explained by mutations in the ERG11B gene. Infections with T. mentagrophytes ITS genotype VIII (T. indotineae) have become a public health issue with potentially global ramifications. About 62% of samples from Bangladesh showed resistance to terbinafine, making oral itraconazole the most effective drug currently available, although resistance to itraconazole and both terbinafine and itraconazole also exists. [ABSTRACT FROM AUTHOR]

Trichophyton indotineae is an emerging pathogen causing recalcitrant skin infections and exhibiting multiple resistances to azoles and allylamines. Squalene epoxidase erg1Ala448Thr mutants often show association with azole resistance. RT-PCR gene expression analysis helps to elucidate the connection between ergosterol biosynthesis regulation and efflux control through the activation of multidrug resistance (MDR) and major facilitator superfamily (MFS1) transporters as well as heat shock proteins (HSP). Several T. indotineae isolates demonstrated a heat-dependent increase of Erg11B transcripts combined with downregulation of Erg1, suggesting a protective role for Erg11B. They also showed persistent upregulation of MFS1. The addition of fluconazole or voriconazole induced the expression of Erg11A, MDR3 and, to a lesser extent, Erg11B and Erg1. The azole-resistant erg1Ala448Thr mutant UKJ 476/21 exhibited exceptionally high transcript levels of sterol 14-αdemethylase Erg11B, combined with the inability of HSP60 and HSP90 to respond to increasing growth temperatures. Itraconazole demonstrated similar effects in a few T. indotineae isolates, but terbinafine did not enhance Erg1 transcription at all. Overexpression of Erg11B may explain the multiple azole resistance phenotype, whereas Erg11B point mutations are not associated with resistance to azoles used for medical treatment. [ABSTRACT FROM AUTHOR]

Background: Trichophyton indotineae, a newly defined species within the T. mentagrophytes/T. interdigitale complex, has emerged as an epidemiological concern worldwide. However, owing to the limitations of commonly applied fungal identification techniques, T. indotineae remains underreported. In addition, T. indotineae's response to treatment has been described in only a few studies. Objective: To investigate the prevalence, clinical characteristics and treatment outcomes of terbinafine‐resistant T. mentagrophytes/T. interdigitale complex infections, as well as to detect T. indotineae cases. Patients and Methods: A retrospective cohort study was conducted on 22 patients with T. mentagrophytes/T. interdigitale complex infections between 2019 and 2023, using either culture or commercial polymerase chain reaction methods. Patient demographics, disease characteristics and treatment responses were recorded. Patients non‐responsive to oral terbinafine underwent further analyses, including DNA sequencing of the internal transcribed spacer region for accurate species identification and mutational analysis of the squalene epoxidase (SQLE) gene. Results: The mean age of the patients was 49.7 years (±18.2), with 54.5% men. Terbinafine‐resistant T. mentagrophytes/T. interdigitale complex infections were reported in 46.2% of the cohort (n = 6/13 patients; 9 lost to treatment response follow‐up), all of whom exhibited extensive dermatophytosis. Among the terbinafine‐resistant T. mentagrophytes/T. interdigitale isolates, all five isolates available for fungal analysis were identified as T. indotineae, harbouring SQLE single‐point mutations (Phe397Leu and Leu393Ser). Only three of the terbinafine‐resistant cases responded to oral itraconazole 200 mg/day, with two responding only to oral voriconazole and one to oral itraconazole 400 mg/day. Conclusion: All cases of T. mentagrophytes/T. interdigitale assessed in this study were identified as T. indotineae, which exhibits SQLE gene mutations. This underscores the importance of integrating methods to detect T. indotineae in routine clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in diagnosing dermatophytomas, a subtype of onychomycosis, characterized by dense fungal masses in the nail plate. The study analyzed patient data to identify clinical, dermoscopic, and histopathologic characteristics of dermatophytomas. Dermatophytomas are difficult to treat and may be underrecognized, with dermoscopy aiding in diagnosis by highlighting central yellow coloration. The study recommends histopathological confirmation and identification of the causative organism through culture or PCR testing. Limitations include a small sample size and the need for further research to improve diagnosis and treatment of dermatophytomas. [Extracted from the article]

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This case study illustrates a 24-year-old Chinese man who presented with tinea capitis associated with a fungal infection. He was administered a therapeutic regimen consisting of terbinafine, ketoconazole cream, and miconazole shampoo for 2 months. However, the symptoms recurred 3 months after the treatment ended. Fungal culture and sequencing confirmed the infection of Hortaea werneckii. Drug sensitivity testing showed that the infecting strain of the patient remained sensitive to the five commonly used antifungal drugs in vitro. While most cases infected by Hortaea werneckii present with Tinea nigra, the possibility of Hortaea werneckii infection should be considered in patients with tinea capitis living in coastal cities. [ABSTRACT FROM AUTHOR]

I report a case of tinea barbae presenting as a tumor in the philtrum of a man in his thirties with comorbid alcoholic liver disease. The patient also had tinea on the auricles, neck, and feet, with direct microscopy confirming the presence of dermatophytes at all sites. A history of multiple pet ownership was noted. The causative organism in the philtrum was identified as the zoophilic fungus Trichophyton mentagrophytes, while the tinea on the feet was caused by the anthropophilic fungus Trichophyton interdigitale ITS genotype II. Despite abnormal liver enzymes, the patient was cured after a three-month course of oral terbinafine following cessation of alcohol intake. This case, encountered by the author approximately 20 years ago, was initially identified as Arthroderma vanbreuseghemii using PCR-RFLP analysis of the ITS region of rRNA genes. Recent sequencing analysis of pre- served strains reidentified the organism as T. mentagrophytes. The alignment of this strain showed a query cover of 100% and a percent identity (Per.ident) of 99.84%, matching with T. mentagrophytes ITS genotype VII. As a dermatologist, it is crucial to continuously monitor the evolving taxonomy of fungi and its clinical implications. [ABSTRACT FROM AUTHOR]

The patient was a girl (case 1) and her mother (case 2). The family had purchased a domestic cat five months previously. Three months later, both patients developed eruptions. Mycological examinations were positive in both cases, and the cat tested positive on the hairbrush test. The macroconidia were thick only in the cat strain, and drug susceptibility testing showed mildly low levels of terbinafine and itraconazole. However, a molecular biological analysis of these three strains showed 100% identity with reference strains of Microsporum canis. Since there have been recent reports of drug-resistant dermatophytosis, drug-susceptibility testing is considered necessary. [ABSTRACT FROM AUTHOR]

Onychomycosis is a prevalent fungal infection of the nails, which causes thickening, discoloration, and detachment of the nail bed. The condition is mainly caused by various fungal species, including dermatophytes, yeasts and molds. Treatment of onychomycosis is complex, with antifungal drugs playing a key role. This research aimed to evaluate the effectiveness of various antifungal treatments, both topical and systemic, in managing onychomycosis. This research used a descriptive qualitative approach, using secondary data through documentation analysis. Data were triangulated to increase reliability and validity. The findings showed that the effectiveness of antifungal treatment varied depending on the type of drug, duration of treatment, and patient compliance. Systemic antifungals, such as terbinafine and itraconazole, showed higher cure rates compared to topical treatments such as ciclopirox and amorolfine. However, all treatments had high relapse rates, underscoring the need for continuous monitoring and customized therapy. The implications of this research demonstrate the importance of personalized treatment plans and the development of strategies to prevent relapse, which remains a significant challenge in the management of onychomycosis. [ABSTRACT FROM AUTHOR]

Recent studies have reported an increase in pediatric onychomycosis prevalence worldwide, suggesting that this population may be increasingly affected by the infection. A summary of the epidemiological impact, antifungal treatment options, special considerations for at‐risk subpopulations, and methods to prevent infection and recurrence are discussed. A systematic review of available epidemiological studies found the worldwide prevalence of culture‐confirmed pediatric toenail onychomycosis to be 0.33%, with no significant increases in prevalence over time. A systematic review of studies investigating the efficacy of various antifungals in treating pediatric onychomycosis found high cure rates and low frequency of adverse events with systemic itraconazole and terbinafine; however, the studies are few, dated, and lack impact because of small sample sizes. Comparatively, clinical trials implementing FDA‐approved topical antifungal treatments report slightly reduced cure rates with larger sample sizes. Patients with immunity‐altering conditions, such as Down's syndrome, or those immunosuppressed because of chemotherapy or HIV/AIDS are at a greater risk of onychomycosis infection and require special consideration with treatment. Proper sanitization and hygiene practices are necessary to reduce the risk of acquiring infection. Early diagnosis and treatment of onychomycosis in children, as well as any affected close contacts, are crucial in reducing the impact of the disease. [ABSTRACT FROM AUTHOR]

Background: In recent decades, globalization and international migration have increased the spread of infectious agents, including dermatophytes. Although considered minor infections, dermatophytoses are highly contagious, and they significantly reduce the quality of life, inducing itching, burning, sleep disturbances, and even depressive states. Moreover, the increasing resistance to antifungals threats the public health and burdens the costs for the healthcare system. Methods: DermaGenius® Resistance Multiplex real-time PCR assay allowed to analyze the terbinafine susceptibility/resistance of 172 Trichophyton strains, which were isolated from human and animal samples collected from 2016 to May 2024 and previously identified by Sanger sequencing. Results: All the 11 animal strains belonged to the T. interdigitale/T. mentagrophytes complex and tested terbinafine sensitive. Out of 161 human strains, 9 (5.6%) showed terbinafine resistance and 7 (4.3%) were identified as T. indotineae. Conclusions: This study provides preliminary data about behavior toward antifungals in animals and finalizes the scientific information currently available about human strains, highlighting the importance of the One Health concept. Moreover, it supports the relevant role of T. indotineae as an emerging dermatophyte with high proportion of terbinafine resistance. [ABSTRACT FROM AUTHOR]

Background: Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvovaginal infections in women. This study aimed to investigate the clinical information and antifungal susceptibility of clinical cases with S. cerevisiae and establish a foundation for the prevention and treatment of fungal infections. Methods: This study was conducted from May 2018 to May 2023 at a national regional medical center in Southwest China for women and children. The demographic and clinical characteristics of patients isolated with S. cerevisiae were collected and analyzed. All the isolates were cultured on Sabouraud medium plates and identified by MALDI-TOF MS. The antifungal susceptibility of S. cerevisiae to 10 agents (amphotericin B, fluconazole, itraconazole, voriconazole, micafungin, caspofungin, terbinafine and 5-flucytosine) was determined via the microdilution broth method to determine the minimum inhibitory concentrations (MICs). Results: A total of 75 cases of S. cerevisiae isolated from patients with vulvovaginal candidiasis (VVC, 44 cases), pneumonia (13 cases), or diarrhea (18 cases) were included after data review. The MICs of voriconazole and flucytosine for S. cerevisiae isolated from different body sites differed, with higher resistance in intestinal isolates. In this study, S. cerevisiae caused VVC, but there was no clear evidence that it was involved in pneumonia or diarrhea. Compared with those of Candida albicans, the primary pathogen of VVC, the MICs of fluconazole (11.96 ± 5.78 µg/mL vs. 67.64 ± 16.62 µg/mL, p = 0.002), itraconazole (0.77 ± 0.19 µg/mL vs. 2.31 ± 0.53 µg/mL, p = 0.008), voriconazole (0.22 ± 0.09 µg/mL vs. 5.02 ± 1.09 µg/mL, p < 0.001), and terbinafine (10.41 ± 0.84 µg/mL vs. 14.93 ± 4.77 µg/mL, p < 0.001) for S. cerevisiae (isolated from the genital tract) were significantly lower, while those of micafungin (0.14 ± 0.01 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) and caspofungin (0.27 ± 0.04 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) were significantly greater. Conclusion: Azoles remain the recommended regimen for S. cerevisiae-related VVC, and the use of amphotericin B vaginal effervescent tablets could be considered for the treatment of azole-resistant isolates. The antifungal susceptibility of S. cerevisiae varies according to the isolated source, and the pathogenicity trend of S. cerevisiae should be studied. Highlights: This is the first clinical Saccharomyces cerevisiae study conducted in East Asia and included 75 cases. S. cerevisiae can cause vulvovaginal candidiasis (VVC), but the difficulty of its treatment is no greater than that of Candida albicans. Azoles are still the recommended regimen for treating S. cerevisiae vulvovaginitis, and resistant isolates are usually susceptible to amphotericin B, for which vaginal effervescent tablets can be used. The antifungal susceptibility of clinical S. cerevisiae isolates may vary among regions, populations, and isolation sites, and attention should be given to the increasing trend of detection in medical institutions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acremonium and the recently separated acremonium-like genera, such as Sarocladium, are emerging causes of opportunistic disease in humans, mainly post-traumatic infections in immunocompetent hosts, but also invasive infections in immunocompromised patients, such as those undergoing transplantation. Acremonium egyptiacum has emerged as the major pathogenic Acremonium species in humans, implicated mainly in nail but also in disseminated and organ specific infections. In this first study of acremonium-like clinical isolates in Greece, 34 isolates were identified and typed by sequencing the internal transcribed spacer, and their antifungal susceptibility was determined by a modified CLSI standard M38 3rd Edition method for filamentous fungi. A. egyptiacum was the primary species (18 isolates) followed by Sarocladium kiliense (8), Acremonium charticola, Gliomastix polychroma, Proxiovicillium blochii, Sarocladium terricola, Sarocladium zeae, and Stanjemonium dichromosporum (all with one isolate). Two isolates, each with a novel ITS sequence, possibly represent undescribed species with an affinity to Emericellopsis. All three A. egyptiacum ITS barcode types described to date were identified, with 3 being the major type. Flutrimazole, lanoconazole, and luliconazole presented the lower minimum inhibitory concentration (MIC) values against A. egyptiacum, with a geometric mean (GM) MIC of 2.50, 1.92, and 1.57 μg/mL, respectively. Amphotericin B, itraconazole, posaconazole, voriconazole, terbinafine, amorolfine, and griseofulvin MICs were overall high (GM 12.79–29.49 μg/mL). An analysis of variance performed on absolute values showed that flutrimazole, lanoconazole, and luliconazole were equivalent and notably lower than those of all the other drugs tested against A. egyptiacum. Antifungal susceptibility of the three different A. egyptiacum genotypes was homogeneous. Overall, the high MICs recorded for all systemically administered drugs, and for some topical antifungals against the tested A. egyptiacum and other acremonium-like clinical isolates, justify the routine susceptibility testing of clinical isolates. [ABSTRACT FROM AUTHOR]

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii. In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle. [ABSTRACT FROM AUTHOR]

Background: Tinea pedis is one of the most prevalent superficial fungal infections. Initial antifungal treatment is often acquired over‐the‐counter (OTC) without previous consultation with a physician. Objective: Lately, increasing antifungal terbinafine resistance has been documented in Denmark and globally and it is therefore of interest to assess how Danish pharmacies advise customers with tinea pedis. Methods: One hundred Danish pharmacies were randomly selected and an employee interviewed from each. A structured question guide was followed, with the possibility to add further comments. Results: Interviews of 94 pharmacies were conducted. Six pharmacies never replied. Terbinafine as standard dose or cutaneous solution terbinafine one time application (Lamisil Once (R)) were recommended by 99% of the pharmacy employees as first‐line treatment. The customer was advised to seek medical attention when tinea pedis was recurring (93%), or when treatment duration was > 2 weeks (77%). The majority (88%) of the pharmacy employees had no knowledge about antifungal resistance. Conclusion: Only few pharmacy employees were aware of the current problem of antifungal resistance and the majority advised costumers to initiate treatment using OTC topical terbinafine. The problem of emerging antifungal resistance requires attention in order to provide customers with tinea pedis effective treatment and prevent further societal spread of resistance to antifungals. [ABSTRACT FROM AUTHOR]

Background: Terbinafine is widely used to treat onychomycosis caused by dermatophyte fungi. Terbinafine resistance in recent years is causing concern. Resistance has so far been associated with single‐nucleotide substitutions in the DNA sequence of the enzyme squalene epoxidase (SQLE) but how this affects SQLE functionality is not understood. Objectives: The aim of this study was to understand newly discovered resistance in two Australian strains of Trichophyton interdigitale. Patients/Methods: Resistance to terbinafine was tested in four newly isolated strains. Three‐dimensional SQLE models were prepared to investigate how the structure of their SQLE affected the binding of terbinafine. Results: This study found the first Australian occurrences of terbinafine resistance in two T. interdigitale strains. Both strains had novel deletion mutations in erg1 and frameshifts during translation. Three‐dimensional models had smaller SQLE proteins and open reading frames as well as fewer C‐terminal α‐helices than susceptible strains. In susceptible strains, the lipophilic tail of terbinafine was predicted to dock stably into a hydrophobic pocket in SQLE lined by over 20 hydrophobic amino acids. In resistant strains, molecular dynamics simulations showed that terbinafine docking was unstable and so terbinafine did not block squalene metabolism and ultimately ergosterol production. The resistant reference strain ATCC MYA‐4438 T. rubrum showed a single erg1 mutation that resulted in frameshift during translation, leading to C‐terminal helix deletion. Conclusions: Modelling their effects on their SQLE proteins will aid in the design of potential new treatments for these novel resistant strains, which pose clinical problems in treating dermatophyte infections with terbinafine. [ABSTRACT FROM AUTHOR]

Background: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N‐acetylcysteine (NAC) and its combinations are limited. Hypothesis/objectives: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE. Materials and methods: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1–5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02–300 µg/mL, 0.04–80 µg/mL, 0.16–40 µg/mL and 1.25–20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis. Results: The MIC90 values of M. pachydermatis were 4.6875–9.375 µg/mL, 1.25 µg/mL, 5–10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively. Conclusions and clinical relevance: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis, a prevalent fungal infection, often exhibits treatment failure. It poses ongoing public health concerns, urging exploration of alternative treatment strategies. This study examines eucalyptol's in vitro activity and its interaction with antifungal agents against dermatophyte isolates. Methods: Overall, 489 patients clinically suspected of dermatophytosis were investigated, and the causative agents were molecularly identified. The antifungal activity of eucalyptol, itraconazole, terbinafine, and griseofulvin was assessed according to the guideline of the Clinical and Laboratory Standards Institute (CLSI M38 ed3). The interaction between eucalyptol and the aforementioned antifungals was determined using a checkerboard method. Results: Dermatophytosis was confirmed in 30 out of 489 (6.13%) patients, with a female-to-male ratio of 3:2 and an age range of 8–67 years. The most commonly observed clinical manifestation was tinea corporis (34.21%), and Trichophyton indotineae (n = 14, 46%) was the most common causative agent. Antifungal susceptibility testing revealed that eucalyptol exhibited antidermatophyte properties with minimum inhibitory concentrations (MIC) ranging from 0.78 to 25 mg/mL. Itraconazole demonstrated the lowest geometric mean (GM) value (MIC range: 0.0019–0.25 µg/mL, GM: 0.015 µg/mL), while griseofulvin exhibited the highest GM value (MIC range: 0.125–8 µg/mL, GM: 2.37 µg/mL). The in vitro interaction of eucalyptol with antifungal drugs, except for its combination with terbinafine against two Trichophyton tonsurans isolates resulting in synergistic effects, showed indifference (n = 70, 77.77%) and antagonistic types (n = 18, 20%). Conclusion: Among the evaluated antifungals, itraconazole demonstrated the highest effectiveness against clinical isolates, while eucalyptol alone exhibited a more pronounced effect than when combined with antifungal agents. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of the Argentine Society of Dermatology / Revista de la Journal Sociedad Argentina de Dermatología is the property of Editorial Biotecnologica S.R.L and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses a rare case of fungal keratitis caused by Tintelnotia destructans, a filamentous fungus that can lead to corneal infections. The patient, a 45-year-old female contact lens wearer, presented with eye pain and redness, leading to a diagnosis of keratomycosis. Treatment with antifungal medications, including natamycin and terbinafine, resulted in the resolution of the infection. The study highlights the importance of early diagnosis and appropriate treatment for fungal keratitis, emphasizing the need for further research on effective management strategies. [Extracted from the article]

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.