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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]

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]

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]

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]

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]

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]

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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: 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]

Abstract 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.

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]

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.

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: 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]

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]

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]

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]

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]

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]

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]