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Cerebral aspergillosis in a patient treated with acalabrutinib, a second generation Bruton's tyrosine kinase inhibitor 阿卡拉布替尼治疗的脑曲霉病患者,第二代布鲁顿酪氨酸激酶抑制剂
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-10-20 DOI: 10.1016/j.mycmed.2025.101586
Scheherazade Rezig , Jean-Philippe Talarmin , Solène Le Gal , Hussam Saad
Bruton’s tyrosine kinase (BTK) inhibitors are key drugs in the frontline therapy of chronic lymphocytic leukemia. Invasive fungal infection is a well-documented adverse event in patient treated with first-generation BTK inhibitors. This rare but severe adverse event has been described in several case-reports and series in patients receiving ibrutinib, particularly invasive aspergillosis, especially of cerebral location. Second-generation BTK inhibitors such as acalabrutinib are more selective for BTK and are as effective and better tolerated than ibrutinib. Only six case-reports have described an opportunistic fungal infection occurring with second-generation BTK inhibitors. Here, we report the case of a patient who developed fatal invasive pulmonary and cerebral aspergillosis while being treated with acalabrutinib.
布鲁顿酪氨酸激酶(BTK)抑制剂是慢性淋巴细胞白血病一线治疗的关键药物。侵袭性真菌感染是第一代BTK抑制剂治疗患者的不良事件。这种罕见但严重的不良事件已在接受伊鲁替尼的患者的几个病例报告和系列中描述,特别是侵袭性曲霉病,特别是大脑部位。第二代BTK抑制剂如阿卡拉布替尼对BTK具有更强的选择性,与依鲁替尼一样有效且耐受性更好。只有6个病例报告描述了第二代BTK抑制剂发生的机会性真菌感染。在这里,我们报告的情况下,患者谁发展致命的侵袭性肺和脑曲霉病,而接受阿卡拉布替尼治疗。
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引用次数: 0
Molecular characterization and antifungal susceptibility profile of Podospora bulbillosa keratitis: case series and review of literature 球孢足孢角膜炎的分子特征和抗真菌敏感性分析:病例系列和文献综述。
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-10-11 DOI: 10.1016/j.mycmed.2025.101585
Sourav Das , Amrita Mohanty , Esther Sheba , Joveeta Joseph

Purpose

Podospora species are rarely reported as etiological agents of keratitis. This study reports a series of fungal keratitis caused by Podospora bulbillosa, detailing their clinical presentation, treatment outcomes, in vitro antifungal susceptibility and molecular characterization.

Methods

Cases of fungal keratitis caused by Podospora bulbillosa between January-March 2025, were retrospectively reviewed from the electronic medical records (EMR). Following microbiological work up, fungal identification was confirmed by large subunit 28S and internal transcribed spacer (ITS) region sequencing and molecular phylogenetic tree was constructed by Maximum Likelihood method. In vitro antifungal susceptibility testing was conducted using the Clinical & Laboratory Standards Institute (CLSI) broth microdilution method (M38-A2).

Results

Five male patients (aged 5–72 years) presented with Podospora bulbillosa keratitis, all following ocular trauma as the predisposing factor. Clinical presentation included central or paracentral pigmented plaque-like stromal infiltrates with surrounding edema and varying degrees of thinning and hypopyon in advanced cases. All patients received topical natamycin 5 % as primary therapy; while one case involved polymicrobial infection with Corynebacterium pseudodiphtheriticum. Three patients showed clinical resolution with scarring following medical management alone. All Podospora bulbillosa isolates showed low MICs (0.03–0.125 µg/mL) to natamycin, azoles, echinocandins, and amphotericin B, indicating potent in vitro activity.

Conclusion

Notably, all five P. bulbillosa isolates clustered within a single subclade, indicating close genetic relatedness. Podospora bulbillosa keratitis responds well to standard antifungal agents. Molecular tools are crucial for accurate identification of rare, non-sporulating fungal pathogens.
目的:足孢子虫作为角膜炎的病原很少被报道。本研究报道了一系列由球泡孢子虫引起的真菌性角膜炎,详细介绍了它们的临床表现、治疗结果、体外抗真菌敏感性和分子表征。方法:回顾性分析2025年1 - 3月电子病历(EMR)中因球泡足孢子虫引起的真菌性角膜炎病例。微生物学鉴定后,采用大亚基28S和ITS区测序法对真菌进行鉴定,并采用极大似然法构建分子系统发育树。采用美国临床与实验室标准协会(CLSI)肉汤微量稀释法(M38-A2)进行体外抗真菌药敏试验。结果:5例男性患者(5 ~ 72岁)出现球囊性足孢子性角膜炎,其易感因素均为眼部外伤。临床表现为中心或中心旁色素斑块样间质浸润伴周围水肿,晚期患者不同程度的变薄和垂体功能减退。所有患者均接受5%的纳他霉素作为主要治疗;1例假性白喉棒状杆菌多微生物感染。3例患者仅在药物治疗后出现疤痕的临床消退。对纳他霉素、唑类、棘白菌素和两性霉素B的mic均较低(0.03 ~ 0.125µg/mL),表明其体外活性较强。结论:值得注意的是,所有5株球孢假单胞菌都聚集在一个亚枝内,表明遗传亲缘关系密切。球孢足孢角膜炎对标准抗真菌药物反应良好。分子工具对于准确鉴定罕见的非孢子真菌病原体至关重要。
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引用次数: 0
Whole genome sequencing of terbinafine-sensitive canine strains of Trichophyton indotineae isolated from India 印度印多毛癣菌特比萘芬敏感犬株全基因组测序。
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-10-09 DOI: 10.1016/j.mycmed.2025.101584
Prasad Thomas , Sonu S. Nair , Mostafa Y. Abdel-Glil , Sudhir K. Prajapati , Subbaiyan Anbazhagan , Shubham Saini , Athira V , Bablu Kumar , Vinod K. Chaturvedi , Shivaprakash M Rudramurthy , G. Saikumar , Premanshu Dandapat , Abhishek

Background

Trichophyton indotineae (earlier Trichophyton mentagrophytes ITS genotype VIII) is a newly defined dermatophyte species frequently reported from India. The strains representing T. indotineae cause dermatophytosis in humans, and some strains exhibit resistance to terbinafine.

Objective

This study aims to characterize the animal strains of T. indotineae at the genomic level and compare them with human strains and other Trichophyton species.

Methods

In this study, we report the generation of de novo WGS data for two strains of T. indotineae isolated from canines of northern India. The genome sequence was subjected to functional and structural annotation, followed by comparative genomics and phylogeny.

Results

Genome assembly and annotation revealed a 22 Mb genome in both strains, comprising approximately 6800 protein-coding genes, and a 24 Kb contig representing the mitochondrion. Functional annotations revealed the presence of around 200 CAZymes and secretomes. The identified proteins include various proteolytic enzymes, such as keratinases, lyases, fungalysins, subtilisins, and chitinases. Orthologous cluster comparison among T. indotineae and T. rubrum identified a LysM effector virulence factor associated with the sequestration of chitin oligosaccharides unique to T. indotineae. Taxonomic inferences involving 69 species representing the Genus Trichophyton revealed similar clustering in genome ANI, mash distance, and core-genome phylogeny. Within all approaches, a total of 16 Indian strains represented T. indotineae. The SNP difference between any two T. indiotinae strains ranged from 8 to 257, indicating limited strain variation within the species. The core-genome phylogeny revealed two major clusters, with no cluster indicating a specific host association. Correlating their phenotypic susceptibility to the anti-fungal drug terbinafine (TRB), the coding sequences (CDS) maintained no amino acid substitutions at key positions 393 and 397. The comparative analysis of the squalene epoxidase gene across the 16 strains revealed a high frequency of SNPs at the 397th position in the squalene epoxidase genes in terbinafine-resistant strains.

Conclusion

To conclude, the study indicates similar genome composition in strains of T. indiotineae from canine and human origin, irrespective of the TRB resistance phenotype. The pathogen and genotypes circulating among humans and animals need to be continuously monitored to determine the exact role of animals in the transmission and endemicity of T. indotineae in India.
背景:印度毛癣菌(Trichophyton indottineae,早期的毛癣菌ITS基因型VIII)是一种新定义的皮癣菌,经常在印度报道。代表indottineae的菌株引起人类皮肤癣病,一些菌株对特比萘芬具有抗性。目的:从基因组水平对印多毛癣菌动物菌株进行鉴定,并与人类和其他毛癣菌进行比较。方法:在本研究中,我们报道了从印度北部犬类中分离的两株印度乳杆菌的新生WGS数据。基因组序列进行了功能和结构注释,然后进行了比较基因组学和系统发育。结果:基因组组装和注释显示,两株菌株的基因组均为22 Mb,包括约6800个蛋白质编码基因和24 Kb代表线粒体的基因组。功能注释显示存在大约200个CAZymes和secretome。鉴定的蛋白质包括各种蛋白水解酶,如角化酶、裂解酶、真菌酶、枯草菌素和几丁质酶。通过对赤藓藓和红藓藓的同源聚类比较,鉴定出一个与赤藓藓特有的几丁质寡糖分离相关的LysM效应毒力因子。对代表毛藓属的69个物种的分类推断显示,在基因组ANI、mash distance和核心基因组系统发育上具有相似的聚类性。在所有的方法中,共有16个印度菌株代表了印蚊。两株不同的单核苷酸多态性(SNP)差异在8 ~ 257之间,表明该菌株在种内变异有限。核心基因组系统发育揭示了两个主要的集群,没有集群表明一个特定的宿主关联。与抗真菌药物特比萘芬(TRB)的表型敏感性相关,编码序列(CDS)在关键位置393和397保持无氨基酸取代。对16株耐特比萘芬菌株的角鲨烯环氧化酶基因进行比较分析,发现在397位角鲨烯环氧化酶基因snp频率较高。结论:综上所述,研究表明犬源和人类源的印蚊菌株的基因组组成相似,与TRB抗性表型无关。需要持续监测在人类和动物中传播的病原体和基因型,以确定动物在印度印蚊传播和流行中的确切作用。
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引用次数: 0
A one health perspective on Diutina catenulata: Phenotypic traits, stress sensitivity, and virulence across diverse isolates 从一个健康的角度来看,在不同的分离株中,毛毛蝶的表型特征、应激敏感性和毒力。
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-18 DOI: 10.1016/j.mycmed.2025.101583
Ianca Karine Prudencio de Albuquerque , Florent Morio , Marjorie Albassier , Luc Baron , Léa Duchesne , Patrice Le Pape , Isabelle Ourliac-Garnier
Diutina catenulata, formerly Candida catenulata, is found in diverse substrates, including soil, food, animals, and humans. It is recognized as an emerging human pathogen responsible for various diseases, including invasive infections in susceptible hosts, particularly in immunocompromised individuals. This study aimed to assess the phenotypic profiles, in vitro responses to various stressful conditions, and in vivo virulence of D. catenulata isolates from different origins (human, veterinary, and environmental). In vitro antifungal susceptibility to fluconazole, voriconazole, micafungin and amphotericin B was also determined for all isolates. Most D. catenulata isolates exhibited a light blue coloration on CHROMID® Candida agar. Different profiles were observed on the Spider medium, suggesting different behavior among the isolates. All isolates of D. catenulata were highly sensitive to oxidative and osmotic stress as demonstrated by exposure to H2O2 and 1.5 M NaCl, respectively whereas no unique pattern was evidenced concerning the response to cell wall stressors or membrane stressors. In addition to acquired azole resistance for some isolates, these findings provide valuable insights into the strain-dependent responses of D. catenulata to various stress factors. Using Galleria mellonella, we highlighted a wide range of virulence profiles among the isolates. Overall, this research demonstrates that the observed responses are strain-dependent rather than sample-source-dependent.
连环假丝酵母(Diutina catenulata),原名连环假丝酵母(Candida catenulata),存在于土壤、食物、动物和人类等多种基质中。它被认为是一种新出现的人类病原体,可导致各种疾病,包括易感宿主,特别是免疫功能低下个体的侵袭性感染。本研究旨在评估来自不同来源(人类、兽医和环境)的D. catenulata分离株的表型特征、对各种应激条件的体外反应和体内毒力。同时测定各菌株对氟康唑、伏立康唑、米卡芬净和两性霉素B的体外抗真菌敏感性。大多数catenulata菌株在CHROMID®假丝酵母琼脂上呈浅蓝色。在蜘蛛培养基上观察到不同的分布,表明不同菌株的行为不同。在H2O2和1.5 M NaCl环境下,所有菌株对氧化胁迫和渗透胁迫均表现出高度敏感,而细胞壁胁迫和膜胁迫均无独特的响应模式。除了一些菌株获得性抗唑外,这些发现还为线虫对各种应激因子的菌株依赖性反应提供了有价值的见解。利用mellonella Galleria,我们在分离株中强调了广泛的毒力概况。总的来说,这项研究表明,观察到的反应是菌株依赖,而不是样品来源依赖。
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引用次数: 0
Tinea capitis in adults: A 14-year retrospective study in central Tunisia 成人头癣:突尼斯中部一项14年回顾性研究。
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-16 DOI: 10.1016/j.mycmed.2025.101582
Hamed Chouaieb , Mohammad Akhoundi , Nadia Ghariani Fetoui , Yasmine Kalboussi , Samar Ismail , Imen Khammari , Sophie Brun , Mohamed Denguezli , Akila Fathallah

Objectives

Tinea capitis (TC) is a common fungal infection predominantly affecting school-aged children while being rare among adults. Few studies, particularly in Tunisia, have specifically focused on TC in adults. This retrospective study aimed to assess the epidemiological and mycological profile of adult TC in central Tunisia (North Africa).

Methods

A retrospective study of adult TC cases diagnosed at the Farhat Hached University Hospital of Sousse, in Tunisia, has been carried out over a 14-year period (2009–2022). Diagnosis was based on clinical presentation and mycological culture. Of 3711 patients examined, 41 adult patients (24 women and 17 men) were diagnosed with TC. The mean age was 43 years old. Ten patients had a history of corticosteroid therapy. Physical examination revealed associated tinea corporis in 6 cases (14.6 %), onychomycosis in 10 cases (24 %) and both those conditions concomitantly in one patient (2.4 %). Direct examination was positive in 97.5 % of cases. The most prevalent species of dermatophyte were Trichophyton violaceum (46 %) and Microsporum canis (34 %). In the majority of cases, the course of treatment was favorable.

Conclusion

We highlight TC as an uncommon condition in adults, with a higher prevalence observed in women, particularly postmenopausal women. Adult TC, though uncommon, should be considered in differential diagnoses for scalp lesions in elderly patients due to potential atypical presentations. Trichophyton violaceum is the most frequent species in central Tunisia. Accurate mycological diagnosis and identification of contributing factors remain crucial.
目的:头癣(TC)是一种常见的真菌感染,主要影响学龄儿童,而在成人中罕见。很少有研究,特别是在突尼斯,专门关注成人的TC。本回顾性研究旨在评估突尼斯中部(北非)成人TC的流行病学和真菌学特征。方法:对突尼斯苏塞Farhat Hached大学医院诊断的成人TC病例进行回顾性研究,研究时间长达14年(2009-2022年)。诊断依据临床表现和真菌学培养。在接受检查的3711名患者中,41名成年患者(24名女性和17名男性)被诊断为TC。平均年龄为43岁。10例患者有皮质类固醇治疗史。体格检查发现6例(14.6%)伴有体癣,10例(24%)伴有甲真菌病,1例(2.4%)伴有这两种情况。直接检查阳性率为97.5%。最常见的种是紫毛霉(Trichophyton violaceum)和犬小孢子菌(Microsporum canis)(34%)。在大多数情况下,治疗过程是有利的。结论:我们强调TC在成人中是一种罕见的疾病,在女性,特别是绝经后妇女中观察到较高的患病率。成人TC虽然不常见,但由于其潜在的非典型表现,应在老年患者头皮病变的鉴别诊断中予以考虑。紫毛蝗是突尼斯中部最常见的种类。准确的真菌学诊断和确定致病因素仍然至关重要。
{"title":"Tinea capitis in adults: A 14-year retrospective study in central Tunisia","authors":"Hamed Chouaieb ,&nbsp;Mohammad Akhoundi ,&nbsp;Nadia Ghariani Fetoui ,&nbsp;Yasmine Kalboussi ,&nbsp;Samar Ismail ,&nbsp;Imen Khammari ,&nbsp;Sophie Brun ,&nbsp;Mohamed Denguezli ,&nbsp;Akila Fathallah","doi":"10.1016/j.mycmed.2025.101582","DOIUrl":"10.1016/j.mycmed.2025.101582","url":null,"abstract":"<div><h3>Objectives</h3><div>Tinea capitis (TC) is a common fungal infection predominantly affecting school-aged children while being rare among adults. Few studies, particularly in Tunisia, have specifically focused on TC in adults. This retrospective study aimed to assess the epidemiological and mycological profile of adult TC in central Tunisia (North Africa).</div></div><div><h3>Methods</h3><div>A retrospective study of adult TC cases diagnosed at the Farhat Hached University Hospital of Sousse, in Tunisia, has been carried out over a 14-year period (2009–2022). Diagnosis was based on clinical presentation and mycological culture. Of 3711 patients examined, 41 adult patients (24 women and 17 men) were diagnosed with TC. The mean age was 43 years old. Ten patients had a history of corticosteroid therapy. Physical examination revealed associated tinea corporis in 6 cases (14.6 %), onychomycosis in 10 cases (24 %) and both those conditions concomitantly in one patient (2.4 %). Direct examination was positive in 97.5 % of cases. The most prevalent species of dermatophyte were <em>Trichophyton violaceum</em> (46 %) and <em>Microsporum canis</em> (34 %). In the majority of cases, the course of treatment was favorable.</div></div><div><h3>Conclusion</h3><div>We highlight TC as an uncommon condition in adults, with a higher prevalence observed in women, particularly postmenopausal women. Adult TC, though uncommon, should be considered in differential diagnoses for scalp lesions in elderly patients due to potential atypical presentations. <em>Trichophyton violaceum</em> is the most frequent species in central Tunisia. Accurate mycological diagnosis and identification of contributing factors remain crucial.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"35 4","pages":"Article 101582"},"PeriodicalIF":1.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthesis, characterization, and antifungal activity of metallic nanoparticles and simvastatin against fungi that cause superficial infections 金属纳米颗粒和辛伐他汀对引起表面感染的真菌的合成、表征和抗真菌活性。
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-09 DOI: 10.1016/j.mycmed.2025.101580
Diego Henrique Morandi , Maria Gabriela Martins dos Reis , Aline Ratuchne , Ricardo Sérgio Couto de Almeida , Guilherme Fonseca Reis , Luciano Aparecido Panagio
Superficial mycoses present several clinical manifestations, ranging from lesions of the skin and its appendages to progression into disseminated infections. Antifungal resistance to currently available drugs is a global public health concern, necessitating novel antimicrobial compounds. Metal nanoparticles or simvastatin (SIM), via drug repositioning, represent promising avenues. The aims of this study were to synthesize and characterize silver nanoparticles (AgNPs) and selenium nanoparticles (SeNPs) and to evaluate their antifungal activity in combination with simvastatin against T. mentagrophytes, T. rubrum, N. gypsea, C. albicans, C. tropicalis, and M. pachydermatis. Nanoparticles were biosynthesized using the supernatant of L. ornata and characterized by UV–Vis, FTIR, zeta potential analysis, DLS, and EDXRF. Their antifungal activity was assessed via broth microdilution (MIC) and checkerboard assays to evaluate agent interactions. MIC values ranged from 1 to 8.7 µg/mL for AgNPs, 194.5 to 778 µg/mL for SeNPs, and 78 to 312.5 µg/mL for simvastatin. A synergistic effect was observed between AgNPs and simvastatin against T. rubrum and T. mentagrophytes. The L. ornata strain demonstrated the ability to synthesize AgNPs and SeNPs, though further research is required to optimize SeNP production. The tested compounds displayed antifungal activity against most of the species analyzed, highlighting their potential as promising alternatives for treating superficial mycoses and combating antifungal resistance.
浅表真菌病有几种临床表现,从皮肤及其附属物的损伤到进展为播散性感染。对现有药物的抗真菌耐药性是一个全球性的公共卫生问题,需要新的抗菌化合物。通过药物重新定位,金属纳米颗粒或辛伐他汀(SIM)代表了有希望的途径。本研究的目的是合成纳米银粒子(AgNPs)和纳米硒粒子(SeNPs)并对其进行表征,并评价其与辛伐他汀联合使用对植物T. mentagrophytes、T. rubrum、N. gypsea、C. albicans、C. tropicalis和厚皮分枝杆菌的抗真菌活性。利用鸢尾上清液合成纳米颗粒,并通过紫外可见光谱、红外光谱、zeta电位分析、DLS和EDXRF对其进行了表征。通过微量肉汤稀释法(MIC)和棋盘法(棋盘法)评估其抗真菌活性。AgNPs的MIC值为1 ~ 8.7µg/mL, SeNPs的MIC值为194.5 ~ 778µg/mL,辛伐他汀的MIC值为78 ~ 312.5µg/mL。AgNPs与辛伐他汀对红藓和红藓有协同作用。L. ornata菌株显示出合成AgNPs和SeNPs的能力,但需要进一步研究优化SeNP的生产。测试的化合物对大多数分析的物种显示出抗真菌活性,突出了它们作为治疗浅表真菌病和对抗抗真菌耐药性的有希望的替代品的潜力。
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引用次数: 0
Disseminated histoplasmosis in erythematosus systemic lupus: A case report and review 系统性红斑狼疮并发弥散性组织胞浆菌病1例报告及复习
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-09 DOI: 10.1016/j.mycmed.2025.101581
Carlos Solórzano, Johiner Vanegas, Maria Alejandra Caro, Maria Camila Rubio
Histoplasmosis is an endemic mycosis in some regions affecting particularly immunosuppressed individuals. The global prevalence of disseminated histoplasmosis in systemic lupus erythematosus (SLE) patients is <1 %, but rises in endemic areas such as Colombia. Clinical manifestations in those patients are atypical, ranging from non-specific symptoms to severe cases of multi-organ failure. Given its rarity and the nonspecific nature of its symptoms, disseminated histoplasmosis in the context of systemic lupus erythematosus remains a diagnostic challenge.
A 28-year-old female patient with a history of SLE diagnosed in 2009 presented to our clinic in February 2024. The patient reported an acute onset of non-specific symptoms, with a subsequent treatment for a suspected bacterial lung infection and successfully discharged. However, due to persistent fever and ongoing weight loss, she returned for further evaluation. Initially a thoracic computed tomography and fiberoptic bronchoscopy was performed, with negative results for tuberculosis (TB), however TB treatment was empirically initiated according to imagenological findings. During hospitalization, the patient developed gastrointestinal bleeding, prompting further investigations and confirming Histoplasma capsulatum in a biopsy. Despite the antifungal therapy, the patient’s condition deteriorated, culminating in multiorgan failure and death 10 days later.
This case underscores the importance of prompt and accurate diagnosis of disseminated histoplasmosis in patients with SLE. The clinical presentation can mimic a lupus flare or other infectious diseases, potentially delaying the initiation of appropriate therapy. In endemic regions such as Latin America, it is critical to include disseminated histoplasmosis in the differential diagnosis of febrile illness in immunosuppressed patients.
组织胞浆菌病是一种地方性真菌病,在某些地区尤其影响免疫抑制的个体。系统性红斑狼疮(SLE)患者中弥散性组织胞浆菌病的全球患病率为1%,但在哥伦比亚等流行地区有所上升。这些患者的临床表现是非典型的,从非特异性症状到严重的多器官功能衰竭。鉴于其罕见性和其症状的非特异性,弥散性组织胞浆菌病在系统性红斑狼疮的背景下仍然是一个诊断挑战。患者为女性,28岁,2009年确诊SLE病史,于2024年2月来我院就诊。患者报告急性发作的非特异性症状,随后因疑似细菌性肺部感染接受治疗,并成功出院。然而,由于持续发烧和持续体重下降,她返回进一步评估。最初进行了胸部计算机断层扫描和纤维支气管镜检查,结果为结核(TB)阴性,但根据影像学结果开始了结核病治疗。住院期间,患者出现胃肠道出血,促使进一步调查并在活检中确认荚膜组织浆体。尽管进行了抗真菌治疗,但患者病情恶化,最终导致多器官衰竭,10天后死亡。本病例强调了及时准确诊断SLE患者播散性组织胞浆菌病的重要性。临床表现可以模仿狼疮发作或其他传染病,潜在地延迟适当治疗的开始。在拉丁美洲等流行地区,将播散性组织浆菌病纳入免疫抑制患者发热性疾病的鉴别诊断是至关重要的。
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引用次数: 0
Novel antifungal activity of broxyquinoline against ITC-Resistant mutants via inhibition of methionine aminopeptidase in Aspergillus fumigatus 溴喹啉通过抑制烟曲霉中蛋氨酸氨基肽酶对itc抗性突变体的新型抗真菌活性
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-02 DOI: 10.1016/j.mycmed.2025.101577
Peiying Chen , Siyuan Tao , Simin Xu , Yangyang Yong , Fei Gao , Yuan Chen , Chujie Lu , Wei Lin

Background

A rising public health threat of invasive aspergillosis causing by azole-resistant Aspergillus species necessitates the development of novel antifungal agents. We performed a screening of antifungal compounds against azole-resistant fungi and broxyquinoline was identified. Our aim was to investigate its antifungal activities and antifungal mechanism.

Methods

Fungal susceptibility testing for broxyquinoline carried out by the broth-based microdilution methods. Cell viability treated by broxyquinoline was tested by resazurin dye testing. The synergistic effect of broxyquinoline and itraconazole was evaluated using checkboard assay. Enzyme activity was investigated with spectrophotometric methods. The key amino acid residues in the binding of broxyquinoline with A. fumigatus methionine aminopeptidase (AfMetAP) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays.

Results

Broxyquinoline has fungicidal activity against azole-resistant A. fumigatus and synergistic effects with itraconazole. Moreover, we discovered that broxyquinoline is strong inhibitor of AfMetAP through interacting with key residues T279A/W280A of AfMetAP1 and Y527A of AfMetAP2, and in vivo, the strains with high expression of AfMetAP are resistant to BQ.

Conclusions

Broxyquinoline has antifungal activities against azole-resistant Aspergillus spp. and is also a potentiator of ITC in vitro. AfMetAP may biologically targets to BQ in vivo regulating antifungal activity. T279A/W280A of AfMetAP1 and Y527A of AfMetAP2 are key amino acid sites to maintain stable interactions between broxyquinoline and target enzymes AfMetAP.
背景:由抗唑曲霉引起的侵袭性曲霉病对公众健康的威胁越来越大,因此有必要开发新的抗真菌药物。我们进行了抗真菌化合物对唑耐药真菌的筛选和鉴定溴喹啉。我们的目的是研究其抗真菌活性和抗真菌机制。方法采用微稀释法对溴喹啉进行真菌药敏试验。采用复蓝素染色法检测溴喹啉处理后的细胞活力。采用棋盘法评价溴喹啉与伊曲康唑的协同作用。用分光光度法测定酶活性。通过结构分析、定点诱变和微尺度热电泳(MST)等方法确定了溴喹啉与烟曲霉甲硫氨酸氨基肽酶(AfMetAP)结合的关键氨基酸残基。结果溴喹啉对耐唑烟曲霉有一定的杀菌活性,并与伊曲康唑有协同作用。此外,我们通过与AfMetAP1的关键残基T279A/W280A和AfMetAP2的关键残基Y527A相互作用,发现溴喹啉是AfMetAP的强抑制剂,并且在体内,AfMetAP高表达的菌株对BQ具有抗性。结论溴喹啉对抗唑曲霉具有一定的抗真菌活性,是体外ITC增强剂。AfMetAP可能是生物靶点BQ在体内调节抗真菌活性。AfMetAP1的T279A/W280A和AfMetAP2的Y527A是维持溴喹啉与靶酶AfMetAP稳定相互作用的关键氨基酸位点。
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引用次数: 0
Terbinafine-resistant Trichophyton indotineae in two Italian MSM: a new emerging sexually transmissible infection 特比萘芬耐药在两个意大利男男性接触者:一种新出现的性传播感染
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-02 DOI: 10.1016/j.mycmed.2025.101578
Luigi Pisano , Deborah Cruciani , Silvia Crotti , Manuela Papini
We report, to the best of our knowledge, the first two cases of Trichophyton (T.) indotineae infection observed in a couple of Italian engaged men who have sex with men (MSM), potentially acquired through sexual contact with a third man from India.
This article also provides a narrative review of the most recent existing literature on the potential sexual transmission of genital dermatophytoses. For dermatophytosis sexual transmission is a presumptive diagnosis but some clinical criteria may raise suspicion of sexual transmission, such as the occurrence of genital lesions in individuals with high-risk sexual behavior, without simultaneous involvement of the feet and/or nails, without a history of contact with infected animals, and the presence of similar lesions in sexual partners.
In recent years, several reports have indicated a potential sexual transmission of genital dermatophytosis, mainly caused by T. mentagrophytes genotype VII (TMVII), first observed in heterosexual individuals and then also in groups of MSM, suggesting a potentially unnoticed epidemic at the European level. From 2020 onwards, the emergence of T. indotineae, a novel strain closely related to TMVII, yet often associated with Terbinafine resistance, has been documented in more than 30 countries worldwide. Laboratory identification requires advanced molecular techniques, as culture-based methods are unable to differentiate T. indotineae from other Trichophyton species. A proper species-level diagnosis is essential to establish the appropriate treatment. Dermatologists should be aware of the international spread of this new strain and its potential sexual transmission and conduct targeted mycological tests in at-risk populations.
我们报告,据我们所知,在一对意大利已婚男子(MSM)中观察到的头两例印度毛癣菌(T.)感染,可能是通过与来自印度的第三名男子的性接触获得的。这篇文章也提供了一个叙述性的审查,最近的现有文献对生殖器皮癣的潜在性传播。对于皮肤真菌病,性传播是一种推定诊断,但某些临床标准可能引起对性传播的怀疑,例如在有高风险性行为的个体中出现生殖器病变,脚和/或指甲未同时受损伤,无与受感染动物接触史,以及性伴侣中存在类似病变。近年来,一些报告表明生殖器皮肤真菌病的潜在性传播,主要由T. mentagrophytes基因型VII (TMVII)引起,首先在异性恋个体中观察到,然后在男男性接触者群体中也观察到,这表明在欧洲一级可能未被注意到的流行病。从2020年起,在全球30多个国家出现了与TMVII密切相关的新型菌株T. indotineae,但通常与特比萘芬耐药性有关。实验室鉴定需要先进的分子技术,因为基于培养的方法无法将T. indottineae与其他毛癣菌区分开来。适当的物种水平诊断对于确定适当的治疗方法至关重要。皮肤科医生应意识到这种新菌株的国际传播及其潜在的性传播,并在高危人群中进行有针对性的真菌学检测。
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引用次数: 0
Performance of recombinase polymerase amplification-based assay (RPA) for rapid detection of fungal pathogens in clinical samples of patients in Abidjan, Côte d’Ivoire 重组酶聚合酶扩增法(RPA)快速检测阿比让Côte科特迪瓦患者临床样本中真菌病原体的性能
IF 1.8 4区 医学 Q3 MYCOLOGY Pub Date : 2025-09-02 DOI: 10.1016/j.mycmed.2025.101579
David Koffi , Francis K. Kouadjo , Stephane T. Koui , Kader Diarrassouba , Benjamin Djedji , Jon Salmanton-García , Valerie Ira-Bonouman , Joseph A. Djaman , Andre O. Toure

Background

The diversity of fungal species involved in medical mycology and the increasing rates of resistances make antifungal therapy increasingly challenging. A strategic approach aims to prevent the spread of resistant fungal pathogens and address the prolonged culture time required for fungal identification. The identification of microscopic fungi in biological samples has gained growing interest in molecular biology. The promising isothermal amplification technique can overcome the shortcomings of conventional methods by offering a short reaction time, as well as high specificity and sensitivity.

Objective

This study was initiated to develop a rapid method for identifying fungi from patient biological samples.

Materials.and.Methods

Ninety biological samples were collected from patients and various anatomical sites. The samples were cultured, and DNA extraction was performed on the isolates and biological products. The obtained DNA was used for amplification via RPA (Recombinase Polymerase Amplification).

Results

The results demonstrated varying sensitivity and specificity depending on the type of biological sample, with high sensitivity and specificity for mucosal samples (100 %, respectively), followed by those of invasive mycoses (80 % and 67 %, respectively), and superficial mycoses (72 % sensitivity).

Conclusion

The overall sensitivity and specificity of the RPA method across all sample types were elevated, with 92 % and 100 %, respectively.
医学真菌学中真菌种类的多样性和耐药性的增加使得抗真菌治疗越来越具有挑战性。一种战略方法旨在防止耐药真菌病原体的传播,并解决真菌鉴定所需的长时间培养问题。生物样品中微小真菌的鉴定在分子生物学中引起了越来越大的兴趣。等温扩增技术具有反应时间短、特异度高、灵敏度高等优点,克服了传统方法的不足。目的建立一种快速鉴定患者生物标本中真菌的方法。材料和方法从患者和不同解剖部位收集90份生物标本。对样品进行培养,对分离物和生物制品进行DNA提取。获得的DNA通过RPA (Recombinase Polymerase amplification)进行扩增。结果不同生物样品的敏感性和特异性不同,其中粘膜样品的敏感性和特异性较高(分别为100%),其次是侵袭性真菌病(分别为80%和67%),浅表真菌病(分别为72%)。结论RPA法在所有样品类型中的总体敏感性和特异性均有提高,分别为92%和100%。
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Journal de mycologie medicale
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