terbinafine

特比萘芬
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  • 文章类型: Journal Article
    所述毛癣菌复合体包含负责各种皮肤病感染的一组皮肤癣菌真菌。这种复杂的物种不断增加的抗药性,特别是对墨发毛癣菌的特比萘芬抗性,是皮肤科医生实践中的一个主要问题。这项研究提供了从顺化市-越南患者中分离出的T.mentagrosphytes复杂菌株的综合分析,关注它们的表型和遗传特征,抗真菌药敏谱和分子流行病学。从形态学和表型上鉴定了皮肤癣菌培养样品中的角质形成性真菌,通过ITS测序和系统发育分析确认的物种和基因型。进行抗真菌药敏试验以评估其对伊曲康唑的敏感性,伏立康唑和特比萘芬.24%(n=27/114)的浅表真菌病在表型上归因于T.T.interdigitale,主要是基因型II*,占主导地位(44.4%),其次是T.stagagrosphytes基因型III*(22.2%),吲哚科(14.8%),T、吨苏兰(11.2%),和T.植叶植物(7.4%)。虽然所有分离株对伊曲康唑和伏立康唑敏感,一半的吲哚虫分离株对特比萘芬表现出耐药性,与SQLE蛋白中的Phe397Leu突变有关。这项研究强调了越南存在耐特比萘芬T.indotineae分离株,强调有必要调查皮肤癣菌的耐药性,并在临床实践中采取有效措施。
    从顺化市皮肤癣菌病中分离出的毛癣菌复合体中的物种多样性,越南,被观察到。越南首次检测到耐特比萘芬的吲哚毛癣菌,强调实施抗真菌药敏试验以有效管理和防止耐药分离株传播的重要性。
    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.
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  • 文章类型: Journal Article
    抗真菌耐药的皮肤癣菌感染最近已成为全球公共卫生问题。对美国传染病专家的调查发现,只有65%的人听说过这个问题,只有39%的人知道如何进行检测以确定耐药性。需要提高临床医生的意识并获得抗真菌耐药性皮肤癣菌病的检测。
    Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.
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  • 文章类型: Journal Article
    局部抗真菌药可被考虑用于治疗甲癣,而全身副作用的风险最小。在这项研究中,我们评估安全性,耐受性,全身暴露,和局部盐酸特比萘芬10%溶液(MOB015B)在成人中重度甲癣的药代动力学特征。临床和真菌学证实的脚趾甲真菌病患者(N=20)纳入此单中心,开放标签研究。每位患者都有≥50%的大脚趾甲和至少四个其他脚趾甲受累。MOB015B每天一次应用于所有脚趾甲,持续28天。在第1、14和28天抽血。到24小时,在所有受试者中第一剂量后MOB015B的血浆浓度是可量化的。到第28天,血浆中的稳态水平达到。在第28天,最大血浆浓度(Cmax)的平均全身暴露为0.72ng/mL,比口服250mg特比萘芬28天后的平均血浆水平1.39µg/mL低约2,000倍。不良事件(5名患者)如头痛(n=3),季节性过敏(n=1),和颈部疼痛(n=1),被认为与MOB015B无关;没有观察到由于不良事件导致的应用部位反应或研究中断。MOB015B在28天的最大使用条件下应用于所有受影响的脚趾甲,显示血浆中特比萘芬水平非常低(28天后Cmax<1ng/mL),符合良好的安全性和耐受性。
    结果:本研究在ClinicalTrials.gov注册为NCT03244280。
    Topical antifungals may be considered to treat onychomycosis with minimal risk of systemic side effects. In this study, we assess the safety, tolerability, systemic exposure, and pharmacokinetic characteristics of topical terbinafine hydrochloride 10% solution (MOB015B) in adults with moderate-to-severe onychomycosis. Clinically and mycologically confirmed patients with toenail onychomycosis (N = 20) were enrolled in this single-center, open-label study . Each patient had ≥50% involvement of both great toenails and at least four additional toenails affected. MOB015B was applied once daily to all toenails for 28 days. Blood was drawn on days 1, 14, and 28. Plasma concentrations of MOB015B after the first dose were quantifiable in all subjects by 24 h. Steady-state levels in plasma were reached by day 28. The mean systemic exposure on day 28 of 0.72 ng/mL for maximum plasma concentration (Cmax) was approximately 2,000 times lower than the mean plasma level of 1.39 µg/mL seen after oral administration of 250 mg terbinafine for 28 days. Adverse events (five patients), such as headache (n = 3), seasonal allergy (n = 1), and neck pain (n = 1), were considered unrelated to MOB015B; no application site reactions or study discontinuations due to an adverse event were observed. MOB015B applied to all affected toenails under maximal usage conditions for 28 days demonstrated very low levels of terbinafine in plasma (Cmax <1 ng/mL after 28 days), consistent with a favorable safety and tolerability profile.
    RESULTS: This study is registered with ClinicalTrials.gov as NCT03244280.
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  • 文章类型: Journal Article
    背景:特比萘芬已成功用于治疗人孢子丝菌病;然而,其在治疗猫孢子丝菌病中的有效性尚不清楚。因此,本研究旨在描述特比萘芬在治疗猫孢子丝菌病中的应用。
    方法:在孢子丝菌病的猫中进行了一项队列研究,以评估特比萘芬(30〜60mg/kg/天)的有效性和安全性。每月进行临床检查和实验室参数分析,直到临床症状消退或停用特比萘芬治疗。
    结果:在研究中纳入的54只孢子丝菌病猫中,19人在随访期间丢失,5人由于改用另一种处方药治疗而退出研究。剩下的30只猫,10取得临床治愈,中位治疗时间为18.5周。18例治疗失败,两只猫死了.二十二只猫对特比萘芬治疗有不良反应,和10只猫显示血清转氨酶升高。
    结论:随访期间的损失很高,这使得很难得出关于临床结果的准确结论。
    结论:观察到的临床治愈率低表明特比萘芬不是猫科动物孢子丝菌病病例的有效治疗选择。
    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.
    CONCLUSIONS: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes.
    CONCLUSIONS: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.
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  • 文章类型: Journal Article
    Introduction.孢子丝菌病是由嵌入临床进化枝的双态孢子丝菌引起的皮下感染。真菌有毒力因子,如生物膜和黑色素的产生,这有助于他们的生存,并与治疗失败病例数量的增加有关,这使得有必要搜索新的选项。差距声明。质子泵抑制剂(PPIs)已被证明可以抑制其他真菌的生长和黑素生成。瞄准.因此,这项研究旨在评估奥美拉唑(OMP)的效果,雷贝拉唑(RBP),埃索美拉唑,泮托拉唑和兰索拉唑对孢子丝菌的易感性和黑素生成,以及它们与伊曲康唑的相互作用,特比萘芬和两性霉素B.使用微量稀释法评估PPI的抗真菌活性,以及PPI与伊曲康唑的组合,使用棋盘法评估特比萘芬和两性霉素B.黑素生成抑制的评估使用灰度评估。结果。OMP和RBP分别显示了32至256µgml-1和32至128µgml-1的显着MIC结果。生物膜很敏感,在512µgml-1的浓度下,OMP的代谢活性显着降低了52%,RBP的代谢活性显着降低了50%,在512µgml-1的浓度下,OMP的生物量降低了53%,RBP的生物量降低了51%。至于黑素生成的抑制,只有OMP表现出抑制作用,减少54%。结论。结论是PPIsOMP和RBP在体外对孢子丝菌的浮游细胞和生物膜具有抗真菌活性,此外,OMP可以抑制孢子丝菌的黑化过程。
    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.
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  • 文章类型: Journal Article
    特比萘芬可能会导致亚急性皮肤红斑狼疮(SCLE),并分析其临床特点。
    我们收集了1997年至2023年有关特比萘芬诱导的SCLE的文献,以进行回顾性分析。包括37例患者(33例女性和4例男性)。
    患者的中位年龄为49.5岁(范围18-79),发病时间为5周(范围1-12)。SCLE主要表现为环状红斑(83.3%),鳞状红斑(44.4%)和斑丘疹性红斑(13.9%)。组织病理学表现以淋巴细胞浸润为主(55.6%),角化过度(38.9%)和角化细胞坏死(38.9%)。阳性免疫学指标主要包括抗核抗体(100.0%),抗Ro/SSA抗体(94.1%)和抗La/SSB抗体(72.2%)。既往病史通常包括光敏性(33.3%),炎性疾病(33.33%)和红斑狼疮(12.1%)。特比萘芬停药和局部皮质类固醇治疗后,症状在中位时间35天(范围7-84)内完全缓解。全身性皮质类固醇,羟氯喹和免疫抑制剂。随访12个月(范围1.5-48)内未观察到复发。
    这些结果表明,应根据临床症状全面诊断特比萘芬引起的SCLE,组织病理学表现,免疫学参数,和过去的病史。当SCLE发生时,特比萘芬应立即停用,而全身和局部皮质类固醇联合羟氯喹可能是一种有效的治疗方法。
    UNASSIGNED: Terbinafine may cause subacute cutaneous lupus erythematosus (SCLE), and we aimed to analyze its clinical characteristics.
    UNASSIGNED: We collected literature on terbinafine-induced SCLE from 1997 to 2023 for retrospective analysis. Thirty-seven patients (33 females and 4 males) were included.
    UNASSIGNED: The patients have a median age of 49.5 years (range 18-79) and onset time of 5 weeks (range 1-12). SCLE is mainly manifested as annular erythematous (83.3%), scaly erythematous (44.4%), and maculopapular erythematous (13.9%). Mainly, histopathological manifestations are lymphocytic infiltrate (55.6%), hyperkeratosis (38.9%) and keratinocyte necrosis (38.9%). Positive immunological parameters mainly include antinuclear antibody (100.0%), anti-Ro/SSA antibody (94.1%), and anti-La/SSB antibody (72.2%). Past medical history usually includes photosensitivity (33.3%), inflammatory disease (33.33%), and lupus erythematosus (12.1%). Symptoms are completely resolved within a median time of 35 days (range 7-84) after discontinuation of terbinafine and treatment with topical corticosteroids, systemic corticosteroids, hydroxychloroquine, and immunosuppressant. No recurrence was observed within 12 months (range 1.5-48) of follow-up.
    UNASSIGNED: These results suggest that terbinafine-induced SCLE should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and past medical history. Terbinafine should be immediately discontinued when SCLE occurs, while systemic and topical corticosteroids combined with hydroxychloroquine may be an effective treatment.
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  • 文章类型: Journal Article
    甲癣,真菌指甲感染,是日本常见的皮肤病,患病率约为5%-10%。尽管2019年推出了新的抗真菌药物和更新的治疗指南,但实际处方趋势和相关医疗费用的数据有限。本研究旨在使用日本开放数据的国家健康保险索赔和特定健康检查数据库,调查2014财年至2021财年日本甲癣局部和口服抗真菌药物的处方模式和医疗费用。我们分析了四种抗真菌药物的年度处方量和医疗费用:艾氟康唑,卢立康唑,福鲁康唑,还有特比萘芬.艾菲康唑的处方量,2014年推出的一种局部用药,迅速增加并占据市场份额。福瑞康唑,2018年推出的口服药物呈增长趋势,与艾菲康唑处方的下降相吻合。特比萘芬,一种成熟的口服药物,经历了处方量的大幅减少。在老年人中,每10万人的性别和年龄调整处方量较高,特别是艾菲康唑。与2014年相比,2015财年甲癣治疗的总医疗费用增加了一倍以上,主要是由依菲康唑处方推动的,2019-2021财年超过300亿日元。在2020财年和2021财年,成本略有下降,可能是由于引入了福沙康唑。局部处方的优势,尤其是老年人,对于遵循推荐口服抗真菌药物作为甲癣一线治疗的日本指南,人们感到担忧.医疗费用的大幅增加也凸显了甲癣的经济负担和需要具有成本效益的治疗策略。这项研究为日本甲癣治疗的现实世界处方趋势和医疗费用提供了有价值的见解,建议有机会评估指南建议和临床实践之间的潜在差距。
    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.
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  • 文章类型: Journal Article
    特比萘芬,氟康唑,和amorolfine通过在合成途径的不同步骤作用于其靶酶来抑制真菌麦角甾醇的合成,导致各种中间体的积累。我们发现这三种抑制剂对酵母形态的影响是不同的。这些药物通常改变的形态参数的数量仅占总数的约6%。使用理性策略来找到通常变化的参数,我们专注于表型中隐藏的基本相似性,可能是由于麦角固醇水平降低。这导致更高的表观形态相似性。即使使用典型相关分析来选择与基因功能相关的生物学有意义的形态参数,也观察到形态相似性的改善。除了细胞形态的变化,我们还观察到三种抑制剂之间的协同作用以及它们对病原真菌的杀菌效果的差异,可能是由于不同中间体的积累。这项研究提供了对作用于同一生物合成途径的抑制剂的特性的全面了解。
    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.
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