Formulation and Antimycotic Evaluation of Colloidal Itraconazole-Loaded Metered Dose Sprays for Treating Superficial Mycoses.

Commercial topical formulations containing itraconazole (poorly water soluble), for mycotic infections, have poor penetration to infection sites beneath the nails and skin thereby necessitating oral administration. To improve penetration, colloidal solutions of itraconazole (G1-G4) containing Poloxamer 188, tween 80, ethanol, and propylene glycol were prepared and incorporated into HFA-134-containing sprays. Formulations were characterized using particle size, drug content, and Fourier-transform infrared spectroscopy (FTIR). In vitro permeation studies were performed using Franz diffusion cells for 8 h. Antimycotic activity on Candida albicans and Trichophyton rubrum was performed using broth micro-dilution and flow cytometry, while cytotoxicity was tested on HaCaT cell lines. Particle size ranged from 39.35-116.80 nm. FTIR and drug content revealed that G1 was the most stable formulation (optimized formulation). In vitro release over 2 h was 45% for G1 and 34% for the cream. There was a twofold increase in skin permeation, fivefold intradermal retention, and a sevenfold increase in nail penetration of G1 over the cream. Minimum fungicidal concentrations (MFC) against C. albicans were 0.156 and 0.313 µg/mL for G1 and cream, respectively. The formulations showed optimum killing kinetics after 48 h. MFC values against T. rubrum were 0.312 and 0.625 µg/mL for the G1 and cream, respectively. Transmission electron microscopy revealed organelle destruction and cell leakage for G1 in both organisms and penetration of keratin layers to destroy T. rubrum. Cytotoxicity evaluation of G1 showed relative safety for skin cells. The G1 formulation showed superior skin permeation, nail penetration, and fungicidal activity compared with the cream formulation.

Dual quantitative PCR assays for the rapid detection of Trichophyton indotineae from clinical samples.

Trichophyton indotineae is an emerging species of the Trichophyton mentagrophytes complex (TMC), responsible for an epidemic of widespread hairless skin infections that is frequently (50-70%) resistant to terbinafine. In order to initiate appropriate treatment as quickly as possible without waiting for culture positivity (10-15 days) and molecular identification from the strain, we developed a dual quantitative PCR (qPCR) for the direct detection of T. indotineae in clinical samples. We first designed a T. indotineae specific qPCR assay (TI-qPCR) targeting a single specific polymorphism in the internal transcribed spacer region. Although none of the 94 non-dermatophyte and 7 dermatophyte species were amplified, this TI-qPCR allowed amplification of other TMC species at a lower yield. With equal amounts (0.1 ng) of DNA per reaction, the mean quantitative cycle (Cq) values for T. indotineae and non-indotineae TMC were 27.9 (±0.1) and 38.9 (±0.3), respectively. Therefore, we normalised this assay against a previously validated pan-dermatophyte qPCR assay (PD-qPCR) and relied on the ΔCq [(TI-qPCR) - (PD-qPCR)] to identify T. indotineae versus other TMC species. Dual assay was validated using 86 clinical samples of culture-confirmed T. indotinea and 19 non-indotineae TMC cases. The mean ΔCq for non-indotineae TMC was 9.6 ± 2.7, whereas the ΔCq for T. indotinea was -1.46 ± 2.1 (p < 0.001). Setting the ΔCq at 4.5 as a cut-off value resulted in 100% specificity for the detection of T. indotineae. This dual qPCR assay quickly detects T. indotineae from skin scrapings, aiding in early diagnosis and treatment for patients with suspected infection.

Identifying the emerging species Trichophyton indotineae is long and requires to wait for culture positivity. We developed a dual qPCR strategy to detect T. indotineae directly from clinical sample with a 100% sensitivity.

A Road Less Traveled: E-test Method for Antifungal Susceptibility Testing in Trichophyton mentagrophyte Isolates Among Patients Presenting With Dermatophytosis at a Tertiary Healthcare Center in North India.

Introduction Dermatophytosis is a common infection of the skin, hair, and nails caused by dermatophytes, a group of filamentous fungi capable of digesting and obtaining nutrients from keratin. Dermatophytes comprise three important genera: Epidermophyton, Microsporum,and Trichophyton. This study aimed to analyze the antifungal susceptibility patterns of Trichophyton mentagrophytes isolates using the epsilometer test (E-test) method. Material and methods This prospective observational study was conducted on clinically suspected cases of dermatophytosis. All samples, including skin scrapings, hair, and nails, were subjected to potassium hydroxide (KOH) examination followed by fungal culture. The Trichophyton mentagrophytes isolates were then subjected to antifungal susceptibility testing using the E-test method for the two most prescribed antifungals: itraconazole and fluconazole. Results In this study, one-third of the patients who tested positive for dermatophytosis belonged to the same family, with spouses being the most commonly affected. Tinea corporis was the most common clinical presentation, with Trichophyton mentagrophytes identified as the most common etiological agent. Itraconazole was more effective than fluconazole. Conclusion The current study demonstrated that antifungal susceptibility testing of dermatophytes using the E-test is easier and can be applied in routine laboratories as a screening method, serving as an alternative to broth microdilution.

Increased terbinafine resistance among clinical genotypes of Trichophyton mentagrophytes/T. interdigitale species complex harboring squalene epoxidase gene mutations.

Terbinafine resistance has become epidemic as an emerging problem in treatment of dermatohpytosis. This could be attributed in part to a point mutation in the squalene epoxidase (SQLE) gene. In this study, point mutations in the SQLE gene were studied in T. rubrum and T. mentagrophytes/T. interdigitale species complex as two main causative agents of dermatophytosis. Antifungal susceptibility of clinical isolates of T. rubrum (n = 27) and T. mentagrophytes/T. interdigitale (n = 56) was assessed using the M38-3rd edition CLSI method. The SQLE gene and ITS region were sequenced for all the fungal strains, and the mutation sites and genotypes of the terbinafine-resistant strains were characterized. The results demonstrated that, in T. rubrum, the minimum inhibitory concentration of terbinafine (MIC50 and MIC90) was 0.03 µg/ml, and the geometric mean (G mean) concentration was 0.02. For the T. mentagrophytes complex, the MIC50 and MIC90 were 0.03 and 1.0 µg/ml, respectively, and the G mean concentration was 0.04 µg/ml. Four out of the five resistant strains were T. indotineae harboring the F397L and Q408L mutations, while the last one was T. mentagrophytes genotype VII, which harbors the F397L mutation. T. indotineae was the prominent causative agent of terbinafine resistance, with 80 % of the isolates, and T. mentagrophytes genotype VII was introduced as a new genotype in the terbinafine-resistant T. mentagrophytes complex. Our findings further substantiate the importance of antifungal susceptibility testing in selecting the choice of drug for effective treatment of dermatophytosis and highlight the importance of screening dermatophyte species for point mutations responsible for newly developed resistant strains to improve the current knowledge of overcoming infections caused by resistant species.

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

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

Epidemiology of Tinea Capitis Among School-Children in Dschang, Western Cameroon.

Data on the epidemiology of tinea capitis (TC), an infection of the scalp by dermatophytes, are scarce in Cameroon. This study aimed to determine the prevalence of TC among school-children in the Dschang Subdivision, Western Cameroon. A cross-sectional study was carried out in June 2021 in Dschang including pupils aged 5-13. First, a standardized questionnaire was administered to participant for the collection of sociodemographic data. Then, samples were collected and cultured onto Sabouraud-Chloramphenicol-Gentamicin Agar. The etiological agents were identified based on their morphological features and with MALDI-TOF mass spectrometry. A total of 1070 children were clinically examined and 108 (10.1%) children presented with TC lesions. The mean age of the 1070 participants was 8.3 ± 2.6 years (range: 5-13 years); 772 (72.2%) were males. The use of borehole water (OR = 0.01, 95%CI[0.001-0.03]), spring water (OR = 0.2, 95%CI[0.08-0.50]), rainwater (OR = 0.004, 95%CI[0.001-0.016]), and hairdressing salons visits (OR = 0.413, 95%CI[0.196-0.872]) were associated with a decreased TC risk in the multivariate logistic regression analysis. In contrast, sharing bed with siblings (OR = 4.48, 95%CI[2.095-9.60]) was associated with an increased TC risk in children. Among the 32 dermatophytes isolated in culture, Microsporum audouinii was the most frequent (43.8%), followed by Trichophyton rubrum (25.0%) and T. soudanense (25.0%). Microsporum canis and T. violaceum were both rarely isolated. Further studies are warranted to assess the association of TC with domestic water usage that has been highlighted in this study.

Bisphosphonates synergistically enhance the antifungal activity of azoles in dermatophytes and other pathogenic molds.

Superficial infections of the skin, hair, and nails by fungal dermatophytes are the most prevalent of human mycoses, and many infections are refractory to treatment. As current treatment options are limited, recent research has explored drug synergy with azoles for dermatophytoses. Bisphosphonates, which are approved to treat osteoporosis, can synergistically enhance the activity of azoles in diverse yeast pathogens but their activity has not been explored in dermatophytes or other molds. Market bisphosphonates risedronate, alendronate, and zoledronate (ZOL) were evaluated for antifungal efficacy and synergy with three azole antifungals: fluconazole (FLC), itraconazole (ITR), and ketoconazole (KET). ZOL was the most active bisphosphonate tested, displaying moderate activity against nine dermatophyte species (MIC range 64-256 µg/mL), and was synergistic with KET in eight of these species. ZOL was also able to synergistically improve the anti-biofilm activity of KET and combining KET and ZOL prevented the development of antifungal resistance. Rescue assays in Trichophyton rubrum revealed that the inhibitory effects of ZOL alone and in combination with KET were due to the inhibition of squalene synthesis. Fluorescence microscopy using membrane- and ROS-sensitive probes demonstrated that ZOL and KET:ZOL compromised membrane structure and induced oxidative stress. Antifungal activity and synergy between bisphosphonates and azoles were also observed in other clinically relevant molds, including species of Aspergillus and Mucor. These findings indicate that repurposing bisphosphonates as antifungals is a promising strategy for revitalising certain azoles as topical antifungals, and that this combination could be fast-tracked for investigation in clinical trials. IMPORTANCE: Fungal infections of the skin, hair, and nails, generally grouped together as "tineas" are the most prevalent infectious diseases globally. These infections, caused by fungal species known as dermatophytes, are generally superficial, but can in some cases become aggressive. They are also notoriously difficult to resolve, with few effective treatments and rising levels of drug resistance. Here, we report a potential new treatment that combines azole antifungals with bisphosphonates. Bisphosphonates are approved for the treatment of low bone density diseases, and in fungi they inhibit the biosynthesis of the cell membrane, which is also the target of azoles. Combinations were synergistic across the dermatophyte species and prevented the development of resistance. We extended the study to molds that cause invasive disease, finding synergy in some problematic species. We suggest bisphosphonates could be repurposed as synergents for tinea treatment, and that this combination could be fast-tracked for use in clinical therapy.

Terbinafine-resistant T. indotineae due to F397L/L393S or F397L/L393F mutation among corticoid-related tinea incognita patients.

Tinea incognita (TI) can mimic other dermatoses, presenting a diagnostic challenge for dermatologists. In some uncertain cases, it is crucial to accurately identify the causative agent using internal transcribed spacer (ITS) sequencing. The global issue of drug-resistant dermatophytosis is increasing, with Trichophyton (T.) indotineae being the main cause. This study presents four cases of TI (diagnosed as eczema) by terbinafine-resistant T. indotineae strains and reviews the current global TI epidemiology based on geographical continent and related conditions. Furthermore, squalene epoxidase (SQLE)-associated resistance mechanisms are evaluated. Lesions caused by terbinafine-resistant T. indotineae strains do not respond to allylamine antifungals, thus allowing the infection to spread. Among T. indotineae isolates, the SQLE F397L substitution is the most prevalent mutation contributing to azole resistance. F397L and L393F replacements in SQLE were detected in all isolates that exhibited high-level resistance. L393S was seen in isolates with low-resistant strains. Interestingly, and for the first time, an L393F amino acid substitution in the SQLE gene product was detected in the Iranian clinical T. indotineae strain. Also, a genomics-based update on terbinafine resistance that focuses on T. indotineae is discussed in this study.

Trichophyton indotineae, an Emerging Drug-Resistant Dermatophyte: A Review of the Treatment Options.

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.

Fungal Melanonychia: A Systematic Review.

Fungal melanonychia is an uncommon condition, most typically caused by opportunistic melanin-producing pigmented filamentous fungi in the nail plate. In the present study, the clinical characteristics of patients diagnosed with fungal melanonychia were analyzed through a systematic review of cases reported in the literature. The MESH terms used for the search were "melanonychia" AND "fungal" OR "fungi" through four databases: PubMed, SciELO, Google scholar and SCOPUS. After discarding inadequate articles using the exclusion criteria, 33 articles with 133 cases were analyzed, of which 44% were women, 56% were men and the age range was between 9 and 87 years. The majority of cases were reported in Turkey followed by Korea and Italy. Frequent causal agents detected were Trichophyton rubrum as non-dematiaceous in 55% and Neoscytalidium dimidiatum as dematiaceous in 8%. Predisposing factors included nail trauma, migration history, employment and/or outdoor activities. Involvement in a single nail was presented in 45% of the cases, while more than one affected nail was identified in 21%, with a range of 2 to 10 nails. Regarding the clinical classification, 41% evidenced more than one type of melanonychia, 21% corresponded to the longitudinal pattern and 13% was of total diffuse type. Likewise, the usual dermoscopic pattern was multicolor pigmentation. It is concluded that fungal melanonychia is an uncommon variant of onychomycosis and the differential diagnosis is broad, which highlights the complexity of this disease.

The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum.

Trichophyton rubrum is a human fungal pathogen that causes dermatophytosis, an infection that affects keratinized tissues. Integrated molecular signals coordinate mechanisms that control pathogenicity. Transcriptional regulation is a core regulation of relevant fungal processes. Previous RNA sequencing data revealed that the absence of the transcription factor StuA resulted in the differential expression of the MAPK-related high glycerol osmolarity gene (hog1) in T. rubrum. Here we validated the role of StuA in regulating the transcript levels of hog1. We showed through RT-qPCR that transcriptional regulation controls hog1 levels in response to glucose, keratin, and co-culture with human keratinocytes. In addition, we also detected hog1 pre-mRNA transcripts that underwent alternative splicing, presenting intron retention in a StuA-dependent mechanism. Our findings suggest that StuA and alternative splicing simultaneously, but not dependently, coordinate hog1 transcript levels in T. rubrum. As a means of preventing and treating dermatophytosis, our results contribute to the search for new potential drug therapies based on the molecular aspects of signaling pathways in T. rubrum.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Phytochemical inhibitors from Leucas aspera against the target proteins induced by Trichophyton mentagrophytes using computational techniques.

Dermatophytosis is a cutaneous infection that is able to degrade the keratinized tissues of the animal/human body, like skin, nails, and hair, causing chronic or subacute infection with the contact of some specific fungal strains. Trichophyton mentagrophytes are the most potential fungal pathogen causing dermatophytoses. The present study focuses on computationally based in silico antifungal activity of selected phytocompounds of Leucas aspera (Willd.) Link. against dermatophytic fungus, T. mentagrophytes. Validation and screening of derived phytocompounds is performed using Lipinski rule of five and toxicity test through Protox-II. Five target genes involved in dermatophytosis, induced by T. mentagrophytes are retrieved from the UniProt Database, and the corresponding proteins such as glucan 1,3-beta-glucosidase ARB_02797, Probable class II chitinase ARB_00204, squalene monooxygenase, actin, and ubiquitin are selected for in silico study. Three-dimensional structures of the target protein were computationally determined and validated through modeling tools and techniques due to the lack of validated protein structures in the database. Then, these proteins are used for in silico molecular docking through the AutoDock Vina tool to find out the promising phytocompounds. This study could be utilized in designing more effective drugs against T. mentagrophytes. Based on this work, a plant-based natural alternative can be added to the treatment of dermatophytosis rather than synthetic supplements.

Penetration Profiles of Four Topical Antifungals in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.

INTRODUCTION: Onychomycosis is a fungal infection of the nails that can be challenging to treat. Here, matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging was applied to the quantitative analysis of the penetration profile of the antifungal compound, amorolfine, in human mycotic toenails. The amorolfine profile was compared with those of three other antifungals, ciclopirox, naftifine, and tioconazole. METHODS: Antifungal compounds (amorolfine 5% lacquer, ciclopirox 8% lacquer, naftifine 1% solution, and tioconazole 28% solution) were applied to mycotic nails (n = 42). Nail sections were prepared, and MALDI-FTICR analysis was performed on the sections at a spatial resolution of 70 µm to compare the distribution profiles. Based on the minimum inhibitory concentrations of the four test compounds needed to kill 90% (MIC90) of the fungal organism, Trichophyton rubrum, the fold differences between the MIC90 and the antifungal concentrations in the nails (termed the multiplicity of the MIC90) were calculated for each. RESULTS: The penetration profiles indicated higher concentrations of amorolfine and ciclopirox in the deeper layers of the nails 3 h after treatment, compared with naftifine and tioconazole. The mean concentrations across the entire nail sections at 3 h were significantly different among the four antifungals: amorolfine, 2.46 mM; ciclopirox, 0.95 mM; naftifine, 0.63 mM; and tioconazole, 1.36 mM (p = 0.016; n = 8 per compound). The median multiplicity of the MIC90 at 3 h was 191-fold for amorolfine, tenfold for ciclopirox, 52-fold for naftifine, and 208-fold for tioconazole. CONCLUSION: In this study, MALDI-FTICR was successfully applied to the quantitative analysis of antifungal distribution in human mycotic nails. The findings suggest that amorolfine penetrates deeper layers of the nail and accumulates at concentrations far exceeding the MIC needed to exert antimycotic activity.

Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.

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.

Comprehensive Review of Tinea Capitis in Adults: Epidemiology, Risk Factors, Clinical Presentations, and Management.

Tinea capitis is a fungal infection of the scalp and hair caused by dermatophyte molds, that most often affects children and may also affect adults. Previous estimates suggest that between 3% and 11% of all tinea capitis cases worldwide occur in adults, although updated epidemiological studies are needed to reassess the prevalence of tinea capitis in adult populations specifically. Postmenopausal adult women are most often affected by tinea capitis, with African American or Black women particularly at risk. Adults who experience crowded living conditions, who live in close proximity to animals, who are immunosuppressed, and/or who live in households with affected children are at greatest risk of infection. Tinea capitis can be non-inflammatory or inflammatory in nature, and the subtype affects the extent and severity of clinical symptoms. Fungal culture and potassium hydroxide preparations are the most commonly used diagnostic tools. Trichoscopy, defined as dermoscopic imaging of the scalp and hair, is a useful adjunct to the physical examination. The mainstay of therapy is oral antifungal therapy, and topical therapy alone is not recommended. Since tinea capitis infection is uncommon in adults, there are no widely accepted treatment guidelines. Rather, the same medications used for tinea capitis infection among children are recommended for adults at varying doses, including griseofulvin, and terbinafine, and, less commonly, itraconazole and fluconazole. The prognosis for tinea capitis in adults is typically excellent when prompt and adequate treatment is administered; however, delayed diagnosis or inadequate treatment can result in scarring alopecia. Over the past decade, dermatophyte infections resistant to treatment with topical and oral antifungal agents have emerged. While tinea capitis infections resistant to antifungal therapy have been rarely reported to date, antifungal resistance is rising among superficial fungal infections in general, and antifungal stewardship is necessary to ensure that resistance to treatment does not develop among dermatophytes that cause tinea capitis.

Antifungal activity of aminopyrrolnitrin against Trichophyton verrucosum in a guinea pig model of dermatophytosis.

BACKGROUND: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity. OBJECTIVES: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model. METHODS: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 µg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 µg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days. RESULTS: The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 µg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC. CONCLUSION: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.