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 (30â60 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 RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug.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 CoortesRESUMO
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/genéticaRESUMO
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 & purificaçãoRESUMO
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/microbiologiaRESUMO
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 , AdolescenteRESUMO
Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2-4 and 4 µg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.
Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Mutação Puntual , Esqualeno Mono-Oxigenase , Tinha , Humanos , Antifúngicos/farmacologia , Iraque/epidemiologia , Tinha/microbiologia , Tinha/epidemiologia , Tinha/tratamento farmacológico , Farmacorresistência Fúngica/genética , Masculino , Arthrodermataceae/genética , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/patogenicidade , Arthrodermataceae/isolamento & purificação , Feminino , Esqualeno Mono-Oxigenase/genética , Adulto , Filogenia , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Proteínas Fúngicas/genética , IdosoRESUMO
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-IdadeRESUMO
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 , AnfíbiosAssuntos
Antifúngicos , Cetoconazol , Região Lombossacral , Terbinafina , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Terbinafina/uso terapêutico , Terbinafina/administração & dosagem , Cetoconazol/uso terapêutico , Cetoconazol/administração & dosagem , Resultado do Tratamento , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Administração Oral , Animais , Humanos , Cabelo/efeitos dos fármacos , Masculino , Alilamina/análogos & derivadosRESUMO
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 terapêuticoRESUMO
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 terapêuticoRESUMO
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 terapêuticoRESUMO
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% in 49 samples), 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.
Assuntos
Arthrodermataceae , Tinha , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Turquia/epidemiologia , Mar Negro , Qualidade de Vida , Trichophyton , Testes de Sensibilidade Microbiana , Tinha/tratamento farmacológico , Tinha/microbiologiaRESUMO
OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.
Assuntos
Sporothrix , Esporotricose , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Esporotricose/microbiologia , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Terbinafina/uso terapêutico , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Sporothrix/genética , China/epidemiologiaRESUMO
Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.
Assuntos
Antifúngicos , Fungemia , Voriconazol , Humanos , Evolução Fatal , Fungemia/microbiologia , Fungemia/tratamento farmacológico , Fungemia/diagnóstico , Fungemia/complicações , Antifúngicos/uso terapêutico , Masculino , Voriconazol/uso terapêutico , Terbinafina/uso terapêutico , Choque Séptico/microbiologia , Choque Séptico/tratamento farmacológico , Hospedeiro Imunocomprometido , Infecções Oportunistas/microbiologia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/complicações , Quimioterapia Combinada , Pessoa de Meia-Idade , Scedosporium/isolamento & purificaçãoAssuntos
Antifúngicos , Aspergilose , Terbinafina , Humanos , Terbinafina/uso terapêutico , Antifúngicos/uso terapêutico , Resultado do Tratamento , Aspergilose/tratamento farmacológico , Masculino , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Feminino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: 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. AREAS COVERED: 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). EXPERT OPINION: 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.
Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Mutação , Terbinafina , Tinha , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Farmacorresistência Fúngica/genética , Tinha/tratamento farmacológico , Tinha/microbiologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologiaRESUMO
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.
Assuntos
Antifúngicos , Tinha , Trichophyton , Humanos , Antifúngicos/uso terapêutico , Tinha/tratamento farmacológico , Tinha/diagnóstico , Tinha/microbiologia , Trichophyton/efeitos dos fármacos , Trichophyton/genética , Itraconazol/uso terapêutico , Terbinafina/uso terapêuticoRESUMO
A healthy 32-year-old woman presented to clinic with tender pruritic lesions of 2-month duration at the vulva and lesions for weeks on the shins. She was treated with topical corticosteroids and intravenous vancomycin without significant improvement. On examination, dozens of follicular hemorrhagic papulopustules were detected at the suprapubic area and vulva (Figure 1). Similar but less prominent lesions were observed on the shins as well. Biopsies of the vulva and shin revealed a follicular inflammatory infiltrate of neutrophils, histiocytes, and lymphocytes as well as fungal hyphae within the follicular infundibulum and hair shafts, consistent with Majocchi's granuloma (MG). Gram and Fite-Faraco staining, direct immunofluorescence, and bacterial culture were negative. Tissue culture grew Trichophyton mentagrophytes, which was identified using sequence analysis of the D1/D2 region of the 28s rDNA. Minimum inhibitory concentrations for terbinafine, ketoconazole, and itraconazole were determined, with terbinafine having the lowest concentration. Additional history revealed that shortly prior to commencement of her clinical manifestations, the patient had acquired a pet guinea pig with eruptions and hair loss (Figure 2). The patient was prescribed ketoconazole cream and terbinafine, 250 mg daily, with almost immediate improvement. Based on clinical response, the patient remained on terbinafine and ketoconazole cream for 6 months. Her skin remained clear 4 months after discontinuing all antifungals. Based on the results of patient's culture, a veterinarian treated her guinea pig successfully with systemic terbinafine and miconazole lotion.
Assuntos
Cetoconazol , Tinha , Trichophyton , Feminino , Humanos , Animais , Cobaias , Adulto , Terbinafina/uso terapêutico , Cetoconazol/uso terapêutico , Antifúngicos/uso terapêutico , VulvaRESUMO
We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.