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1.
Med Mycol ; 62(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39174488

RESUMO

The Trichophyton mentagrophytes complex comprises a group of dermatophyte fungi responsible for various dermatological infections. The increasing drug resistance of this species complex, especially terbinafine resistance of Trichophyton indotineae, is a major concern in dermatologist practice. This study provides a comprehensive analysis of T. mentagrophytes complex strains isolated from patients in Hue City, Vietnam, focusing on their phenotypic and genetic characteristics, antifungal susceptibility profiles, and molecular epidemiology. Keratinophilic fungi from dermatophytosis culture samples were identified morphologically and phenotypically, with species and genotypes confirmed by internal transcribed spacer sequencing and phylogenetic analysis. Antifungal susceptibility testing was carried out to evaluate their susceptibility to itraconazole, voriconazole, and terbinafine. The 24% (n = 27/114) of superficial mycoses were phenotypically attributed to T. mentagrophytes complex isolates. Trichophyton interdigitale, mainly genotype II*, was predominant (44.4%), followed by T. mentagrophytes genotype III* (22.2%), T. indotineae (14.8%), T. tonsurans (11.2%), and T. mentagrophytes (7.4%). While all isolates were susceptible to itraconazole and voriconazole, half of T. indotineae isolates exhibited resistance to terbinafine, linked to the Phe397Leu mutation in the SQLE protein. This study highlighted the presence of terbinafine-resistant T. indotineae isolates in Vietnam, emphasizing the need to investigate dermatophyte drug resistance and implement effective measures in clinical practice.


Species diversity within the Trichophyton mentagrophytes complex isolated from dermatophytosis in Hue City, Vietnam, was observed. Terbinafine-resistant T. indotineae isolates were detected for the first time in Vietnam, emphasizing the importance of implementing antifungal susceptibility testing to effectively manage and prevent the spread of resistant isolates.


Assuntos
Antifúngicos , Farmacorresistência Fúngica , Genótipo , Testes de Sensibilidade Microbiana , Filogenia , Terbinafina , Tinha , Humanos , Vietnã , Antifúngicos/farmacologia , Terbinafina/farmacologia , Tinha/microbiologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Arthrodermataceae/classificação , Arthrodermataceae/isolamento & purificação , Masculino , Análise de Sequência de DNA , Itraconazol/farmacologia , DNA Espaçador Ribossômico/genética , Feminino , Pessoa de Meia-Idade , DNA Fúngico/genética , Epidemiologia Molecular , Adulto , Trichophyton
2.
Sci Rep ; 14(1): 17093, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107358

RESUMO

Terbinafine, fluconazole, and amorolfine inhibit fungal ergosterol synthesis by acting on their target enzymes at different steps in the synthetic pathway, causing the accumulation of various intermediates. We found that the effects of these three in- hibitors on yeast morphology were different. The number of morphological parameters commonly altered by these drugs was only approximately 6% of the total. Using a rational strategy to find commonly changed parameters,we focused on hidden essential similarities in the phenotypes possibly due to decreased ergosterol levels. This resulted in higher apparent morphological similarity. Improvements in morphological similarity were observed even when canonical correlation analysis was used to select biologically meaningful morphological parameters related to gene function. In addition to changes in cell morphology, we also observed differences in the synergistic effects among the three inhibitors and in their fungicidal effects against pathogenic fungi possibly due to the accumulation of different intermediates. This study provided a comprehensive understanding of the properties of inhibitors acting in the same biosynthetic pathway.


Assuntos
Antifúngicos , Ergosterol , Fenótipo , Ergosterol/metabolismo , Ergosterol/biossíntese , Antifúngicos/farmacologia , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Fluconazol/farmacologia , Vias Biossintéticas/efeitos dos fármacos , Terbinafina/farmacologia
3.
Mycoses ; 67(8): e13778, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39086026

RESUMO

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.


Assuntos
Antifúngicos , Itraconazol , Mutação , Esqualeno Mono-Oxigenase , Terbinafina , Tinha , Trichophyton , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Farmacorresistência Fúngica/genética , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Esqualeno Mono-Oxigenase/genética , Terbinafina/uso terapêutico , Terbinafina/farmacologia , Tinha/tratamento farmacológico , Tinha/microbiologia , Resultado do Tratamento , Trichophyton/efeitos dos fármacos , Trichophyton/genética
4.
J Med Microbiol ; 73(8)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39145374

RESUMO

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.


Assuntos
Anfotericina B , Antifúngicos , Melanogênese , Inibidores da Bomba de Prótons , Sporothrix , Esporotricose , Humanos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Itraconazol/farmacologia , Melaninas/biossíntese , Melaninas/metabolismo , Melanogênese/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Sporothrix/efeitos dos fármacos , Sporothrix/metabolismo , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia , Terbinafina/farmacologia
5.
J Dermatol ; 51(9): 1172-1179, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115330

RESUMO

Onychomycosis, a fungal nail infection, is a common dermatological condition in Japan, with a prevalence of approximately 5%-10%. Despite the introduction of new antifungal medications and updated treatment guidelines published in 2019, data on real-world prescription trends and the associated medical costs are limited. This study aimed to investigate the prescription patterns and medical costs of topical and oral antifungal medications for onychomycosis in Japan from fiscal years 2014 to 2021 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data. We analyzed the annual prescription volumes and medical costs of four antifungal medications: efinaconazole, luliconazole, fosravuconazole, and terbinafine. The prescription volume of efinaconazole, a topical medication launched in 2014, rapidly increased and dominated the market share. Fosravuconazole, an oral medication introduced in 2018, showed an increasing trend, coinciding with a decline in efinaconazole prescriptions. Terbinafine, a well-established oral medication, experienced a substantial decrease in prescription volume. The sex- and age-adjusted prescription volume per 100 000 population was higher among older adults, particularly for efinaconazole. The total medical costs for onychomycosis treatment more than doubled in fiscal year 2015 compared with that for 2014, mainly driven by efinaconazole prescriptions, and exceeded 30 billion Japanese yen in fiscal years 2019-2021. The costs slightly decreased in fiscal years 2020 and 2021, possibly due to the introduction of fosravuconazole. The predominance of topical prescriptions, especially in older adults, raises concerns regarding adherence to the Japanese guidelines that recommend oral antifungals as the first-line treatment for onychomycosis. The substantial increase in medical costs also highlights the economic burden of onychomycosis and the need for cost-effective treatment strategies. This study provides valuable insights into the real-world prescription trends and medical costs of onychomycosis treatment in Japan, suggesting an opportunity to assess potential gaps between guideline recommendations and clinical practice.


Assuntos
Antifúngicos , Bases de Dados Factuais , Onicomicose , Onicomicose/tratamento farmacológico , Onicomicose/economia , Humanos , Japão , Antifúngicos/economia , Antifúngicos/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Administração Tópica , Administração Oral , Prescrições de Medicamentos/estatística & dados numéricos , Prescrições de Medicamentos/economia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/economia , Adulto Jovem , Adolescente , Revisão da Utilização de Seguros , Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Custos de Medicamentos , Terbinafina/uso terapêutico , Terbinafina/economia , Terbinafina/administração & dosagem
6.
Skinmed ; 22(3): 206-207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39090014

RESUMO

A 20-year-old man had developed dermatitis on his scalp and facial hair between his lower lip and chin, his 'soul patch', for one month. He initially presented to urgent care, where the dermatitis was attributed to Herpes simplex infection, for which he was treated with both oral valacyclovir and topical acyclovir. When no change was observed, he consulted his pediatrician, who prescribed oral clindamycin and referred him to dermatology. Physical examination revealed a crusted plaque on an erythematous and edematous base at the lower cutaneous border of the lower lip (Figure 1). Examination additionally revealed an erythematous scaling plaque on the left temporal area with associated flaking, tenderness, and hair loss and left-sided cervical lymphadenopathy. A fungal culture grew Trichophyton mentagrophytes, but a bacterial culture did not grow. Further investigation revealed that he had a dog; however, no other animal contact to account for a fungal reservoir was present. He was successfully treated with oral terbinafine for 6 weeks, plus ketoconazole 2% shampoo and ketoconazole 2% cream with complete reso-lution (Figure 2).


Assuntos
Antifúngicos , Humanos , Masculino , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Adulto Jovem , Cetoconazol/uso terapêutico , Cetoconazol/administração & dosagem , Terbinafina/uso terapêutico , Terbinafina/administração & dosagem , Tinha/tratamento farmacológico , Tinha/diagnóstico , Animais , Cães , Naftalenos/uso terapêutico , Naftalenos/administração & dosagem , Preparações para Cabelo , Trichophyton/isolamento & purificação
7.
Vet Rec ; 195(4): e4435, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39148234

RESUMO

BACKGROUND: Terbinafine has been successfully used in the treatment of human sporotrichosis; however, its effectiveness in the treatment of feline sporotrichosis is unknown. Therefore, this study aimed to describe the use of terbinafine in the treatment of feline sporotrichosis. METHODS: A cohort study was conducted in cats with sporotrichosis to assess the effectiveness and safety of terbinafine (30‒60 mg/kg/day). Clinical examination and analysis of laboratory parameters were performed monthly until clinical signs resolved or terbinafine treatment was discontinued. RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug. Of the remaining 30 cats, 10 achieved clinical cure, with a median treatment time of 18.5 weeks. Treatment failed in 18 cases, and two cats died. Twenty-two cats had adverse reactions to terbinafine treatment, and 10 cats showed elevation of serum transaminases. LIMITATION: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes. CONCLUSION: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.


Assuntos
Antifúngicos , Doenças do Gato , Esporotricose , Terbinafina , Gatos , Animais , Terbinafina/uso terapêutico , Doenças do Gato/tratamento farmacológico , Esporotricose/tratamento farmacológico , Esporotricose/veterinária , Antifúngicos/uso terapêutico , Antifúngicos/efeitos adversos , Resultado do Tratamento , Masculino , Feminino , Estudos de Coortes
9.
Am J Trop Med Hyg ; 111(3): 575-577, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-38981494

RESUMO

Over the past few years, a recalcitrant dermatophytosis has been observed on the Indian subcontinent, including Sri Lanka, which has caused a major public health issue in the region. An emerging species, Trichophyton indotineae, first described as Trichophyton mentagrophytes ITS genotype VIII, is thought to be responsible for this fast-spreading, mostly terbinafine-resistant dermatophytosis. Recalcitrant dermatophytosis is a challenge to dermatologists, and knowing the causative species and antifungal sensitivity in the earlier stage of management would be invaluable. We report a case series of patients with dermatophytosis caused by T. indotineae in Sri Lanka. This is the first detection of this highly terbinafine-resistant strain in Sri Lanka, and existence of this species should be taken seriously by dermatologists and healthcare policymakers for better management of tinea infections and antifungal stewardship in the country.


Assuntos
Antifúngicos , Genótipo , Terbinafina , Tinha , Humanos , Tinha/tratamento farmacológico , Tinha/microbiologia , Sri Lanka , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Masculino , Feminino , Terbinafina/uso terapêutico , Adulto , Pessoa de Meia-Idade , Farmacorresistência Fúngica , Trichophyton/genética , Trichophyton/isolamento & purificação , Trichophyton/efeitos dos fármacos , Trichophyton/classificação , Arthrodermataceae/genética , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/classificação
11.
Eur J Dermatol ; 34(3): 260-266, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-39015959

RESUMO

Onychomycosis, a fungal nail infection, is primarily caused by dermatophytes, yeasts, and non-dermatophyte moulds (NDMs). The incidence of this disease and the predominance of specific pathogens vary across different regions and evolve. This study aimed to elucidate the epidemiology of onychomycosis and the pattern of causative pathogens in Beijing, and to ascertain the in vitro antifungal susceptibility profiles of Trichophyton rubrum against itraconazole (ITR), terbinafine (TER), and fluconazole (FLU). Involving 245 patients of onychomycosis with positive fungal culture results, the study implemented internal transcribed spacer (ITS) sequencing of ribosomal DNA (rDNA) on all collected samples. The mean age of the participants was 37.93 ± 13.73 years, with a male-to-female ratio of 1.53:1. The prevalence of toenail infections was significantly higher than that of fingernails. Distal and lateral subungual onychomycosis (DLSO) were the most frequent clinical classifications. PCR results indicated that dermatophytes were the most prevalent pathogens, followed by yeasts and NDMs, among which T. rubrum was the most dominant dermatophyte. TER demonstrated high sensitivity to T. rubrum. However, in clinical settings, some patients with onychomycosis exhibit a poor response to TER treatment. The relationship between in vitro antifungal sensitivity and clinical effectiveness is complex, and understanding the link between in vitro MIC values and clinical efficacy requires further investigation.


Assuntos
Antifúngicos , Fluconazol , Dermatoses do Pé , Itraconazol , Testes de Sensibilidade Microbiana , Onicomicose , Terbinafina , Humanos , Onicomicose/microbiologia , Onicomicose/tratamento farmacológico , Onicomicose/epidemiologia , Masculino , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Feminino , Adulto , Pessoa de Meia-Idade , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Dermatoses do Pé/microbiologia , Dermatoses do Pé/tratamento farmacológico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Fluconazol/farmacologia , Arthrodermataceae/efeitos dos fármacos , Adulto Jovem , Dermatoses da Mão/microbiologia , Dermatoses da Mão/tratamento farmacológico , Dermatoses da Mão/epidemiologia , China/epidemiologia , Prevalência , Trichophyton/efeitos dos fármacos , Idoso , Adolescente
12.
Mycoses ; 67(7): e13768, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39036952

RESUMO

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.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Onicomicose , Esqualeno Mono-Oxigenase , Terbinafina , Humanos , Onicomicose/microbiologia , Onicomicose/epidemiologia , Onicomicose/tratamento farmacológico , Esqualeno Mono-Oxigenase/genética , Feminino , Pessoa de Meia-Idade , Masculino , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Farmacorresistência Fúngica/genética , Estados Unidos/epidemiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Estudos Longitudinais , Idoso , Arthrodermataceae/genética , Arthrodermataceae/efeitos dos fármacos , Adulto , Mutação , Estudos de Coortes , Trichophyton/genética , Trichophyton/efeitos dos fármacos , Adulto Jovem , Prevalência , Mutação Puntual , Idoso de 80 Anos ou mais , Adolescente , Unhas/microbiologia
13.
Indian J Med Microbiol ; 50: 100621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885904

RESUMO

INTRODUCTION: Tinea capitis, a common scalp infection primarily affecting children, is caused by keratinophilic dermatophytic fungi, notably Microsporum and Trichophyton species. Microsporum canis, primarily transmitted from cats and dogs to humans, is rarely reported in non-endemic regions like India. We report a cases involving three family members from Delhi, India, diagnosed with tinea capitis caused by Microsporum canis. The index case, a five-year-old boy, contracted the infection through contact with a cat, while his younger brother and sister acquired it through human-to-human transmission within the family. METHODS: Clinical examination, microscopic analysis, and molecular identification techniques confirmed the diagnosis. Antifungal susceptibility testing revealed sensitivity to itraconazole and terbinafine but resistance to griseofulvin. RESULTS: Treatment with oral terbinafine and topical ketoconazole cream led to successful outcomes for all three patients. Molecular typing confirmed clonality of the isolates, indicating human-to-human transmission. CONCLUSION: This case study underscores the significance of considering atypical sources of infection and human-to-human transmission in the diagnosis and management of tinea capitis caused by Microsporum canis in non-endemic regions. It emphasizes the necessity of thorough contact history assessment and appropriate antifungal therapy for effective control of the infection.


Assuntos
Antifúngicos , Microsporum , Terbinafina , Tinha do Couro Cabeludo , Humanos , Microsporum/genética , Microsporum/isolamento & purificação , Microsporum/classificação , Microsporum/efeitos dos fármacos , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/diagnóstico , Masculino , Índia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Pré-Escolar , Terbinafina/uso terapêutico , Gatos , Feminino , Animais , Testes de Sensibilidade Microbiana , Itraconazol/uso terapêutico , Naftalenos/uso terapêutico , Naftalenos/farmacologia , Resultado do Tratamento , Cetoconazol/uso terapêutico , Tipagem Molecular , Família , Criança , Griseofulvina/uso terapêutico
14.
Mycopathologia ; 189(4): 52, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864945

RESUMO

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.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Esqualeno Mono-Oxigenase , Terbinafina , Tinha , Irã (Geográfico)/epidemiologia , Farmacorresistência Fúngica/genética , Humanos , Antifúngicos/farmacologia , Terbinafina/farmacologia , Estudos Transversais , Tinha/microbiologia , Tinha/epidemiologia , Prevalência , Arthrodermataceae/genética , Arthrodermataceae/efeitos dos fármacos , Masculino , Feminino , Esqualeno Mono-Oxigenase/genética , Adulto , Pessoa de Meia-Idade , Mutação , Idoso , Adulto Jovem , Adolescente , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Criança
16.
J Dtsch Dermatol Ges ; 22(7): 922-934, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38924688

RESUMO

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.


Assuntos
Antifúngicos , Farmacorresistência Fúngica , Terbinafina , Tinha , Trichophyton , Humanos , Tinha/tratamento farmacológico , Tinha/microbiologia , Tinha/genética , Terbinafina/uso terapêutico , Farmacorresistência Fúngica/genética , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Masculino , Trichophyton/genética , Trichophyton/efeitos dos fármacos , Feminino , Mutação/genética , Pessoa de Meia-Idade , Adulto , Esqualeno Mono-Oxigenase/genética , Corticosteroides/uso terapêutico
17.
J Mycol Med ; 34(3): 101495, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38896927

RESUMO

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.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Genótipo , Testes de Sensibilidade Microbiana , Esqualeno Mono-Oxigenase , Terbinafina , Tinha , Terbinafina/farmacologia , Esqualeno Mono-Oxigenase/genética , Farmacorresistência Fúngica/genética , Humanos , Antifúngicos/farmacologia , Tinha/microbiologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Arthrodermataceae/enzimologia , Mutação Puntual , Mutação , Masculino , Feminino , Proteínas Fúngicas/genética , Adulto , Pessoa de Meia-Idade
18.
J Zoo Wildl Med ; 55(2): 453-461, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38875202

RESUMO

Chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has been documented in greater sirens (Siren lacertina) in the wild and in the pet trade. This study evaluated the use of terbinafine-impregnated implants for chytridiomycosis prophylaxis in greater sirens exposed to Bd. Implants were placed intracoelomically in both control (blank implant, n = 4) and treatment (24.5 mg of terbinafine implant, n = 4) groups. Sirens were exposed to Bd zoospores via 24-h immersion bath at 1 and 2 mon postimplant placement. Blood was collected monthly for plasma terbinafine levels, and skin swabs were collected weekly for Bd quantitative PCR. Animals with terbinafine implants had detectable concentrations of plasma terbinafine ranging from 17 to 102 ng/ml. Only one terbinafine-implanted animal had a peak concentration above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml); however, it is unknown how plasma terbinafine concentrations relate to concentrations in the skin. There was no difference between the two treatment groups in clinical signs or Bd clearance rate, and no adverse effects from implants were observed. These findings indicate using intracoelomic drug implants for drug delivery in amphibians is safe; however, terbinafine efficacy in preventing Bd chytridiomycosis in sirens remains unclear. Further investigation of the use of intracoelomic implants and identification of effective drugs and doses in other amphibian species against Bd and other infectious diseases is warranted, as this may provide a practical method for long-term drug delivery in wildlife.


Assuntos
Antifúngicos , Terbinafina , Terbinafina/administração & dosagem , Terbinafina/uso terapêutico , Terbinafina/farmacologia , Animais , Projetos Piloto , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Antifúngicos/farmacocinética , Implantes de Medicamento , Batrachochytrium/efeitos dos fármacos , Masculino , Micoses/veterinária , Micoses/tratamento farmacológico , Anfíbios
19.
Ann Clin Microbiol Antimicrob ; 23(1): 57, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902740

RESUMO

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.


Assuntos
Antifúngicos , Cromoblastomicose , Imiquimode , Itraconazol , Terbinafina , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Imiquimode/uso terapêutico , Humanos , Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Terbinafina/uso terapêutico , Masculino , Resultado do Tratamento , Microscopia Confocal , Pele/patologia , Pele/microbiologia , Pessoa de Meia-Idade
20.
Mycoses ; 67(7): e13760, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38943042

RESUMO

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.


Assuntos
Antifúngicos , Surtos de Doenças , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Microsporum , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Microsporum/efeitos dos fármacos , Masculino , Feminino , Dinamarca/epidemiologia , Adulto , Criança , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Pessoa de Meia-Idade , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/epidemiologia , Griseofulvina/farmacologia , Griseofulvina/uso terapêutico , Pré-Escolar , Adolescente , Adulto Jovem , Tinha/tratamento farmacológico , Tinha/microbiologia , Tinha/epidemiologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Idoso , Fluconazol/farmacologia , Fluconazol/uso terapêutico
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