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Identification of Filamentous Fungi: An Evaluation of Three MALDI-TOF Mass Spectrometry Systems. 丝状真菌的鉴定:三种MALDI-TOF质谱系统的评价。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-06-01 DOI: 10.1111/myc.70078
Isabel Klugherz, Bettina Kölli, Moritz Reinmüller, Birgit Willinger, Eva Leitner, Ivo Steinmetz, Karl Dichtl

Background: Identification of filamentous fungi still poses a major challenge to laboratories. Matrix assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS) is a promising tool, since it offers low-cost and fast results. Different MALDI-TOF MS systems are available for routine laboratories. This is a comprehensive head-to-head comparison of three devices and the respective reference spectrum databases.

Materials and methods: A set of 77 pre-characterised isolates of filamentous fungi was measured (in duplicates) parallelly with three MALDI-TOF MS systems after 24 h, 48 h and 72 h of incubation: (1) Biotyper smart ('BT', Bruker Daltonics),(2) EXS2600 ('EXS', Zybio) and (3) VITEK MS PRIME ('VITEK', bioMérieux).

Results: After three measurements, no valid results at the species level ('green category') were obtained for 18%, 21% and 14% of isolates by BT, EXS and VITEK. Depending on the MALDI-TOF MS system, validity rates ranged from 58%-82% for the different time points. Correct and valid results were obtained for 82%, 73% and 81% of isolates by BT, EXS and VITEK. BT was the system that required the most duplicate measurements. EXS displayed the highest rate of misidentification events. VITEK had the highest rate of unidentified isolates, which were featured within its database.

Conclusion: Based on our experience, all three devices proved to be suitable for routine diagnostics. The timepoint of measurement had a major impact on the quality of analysis and should be considered by the user. Lowering the validity cut-off levels might increase the performance of the EXS system.

背景:丝状真菌的鉴定仍然是实验室面临的主要挑战。基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)是一种很有前途的工具,因为它提供了低成本和快速的结果。不同的MALDI-TOF质谱系统可用于常规实验室。这是一个全面的头对头比较三个设备和各自的参考频谱数据库。材料和方法:在孵育24小时、48小时和72小时后,用3个MALDI-TOF质谱系统平行测量77个预表征的丝状真菌分离物:(1)Biotyper smart ('BT', Bruker Daltonics),(2) EXS2600 ('EXS', Zybio)和(3)VITEK MS PRIME ('VITEK', biom rieux)。结果:经三次检测,BT、EXS和VITEK法分别检测18%、21%和14%的分离株均未获得物种水平(“绿色类别”)的有效结果。根据MALDI-TOF MS系统,不同时间点的效度在58%-82%之间。BT法、EXS法和VITEK法对分离株的正确率分别为82%、73%和81%。BT是需要重复测量最多的系统。EXS的误认率最高。VITEK具有最高的未识别分离株率,这些分离株在其数据库中具有特色。结论:根据我们的经验,这三种设备都适用于常规诊断。测量的时间点对分析的质量有很大的影响,应该被用户考虑。降低有效性截止水平可能会提高EXS系统的性能。
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引用次数: 0
Comparative Efficacy of Three Oral Itraconazole Formulations in Superficial Dermatophytosis. 三种口服伊曲康唑制剂治疗浅表性皮肤癣的疗效比较。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-06-01 DOI: 10.1111/myc.70080
Harsh Tyagi, Shitij Goel, Aneesha Puri, Isha Singla, Anmol Rathore

Introduction: Dermatophytosis is a chronic public health issue in India, often requiring systemic antifungals. Itraconazole (ITZ) is commonly used, but conventional forms show variable absorption. Super-bioavailable itraconazole (SUBA-ITZ) offers improved pharmacokinetics, though clinical comparisons are limited.

Objective: To compare the efficacy, safety, relapse, and recurrence rates of three oral ITZ formulations-Conventional ITZ 100 mg (C-ITZ), SUBA-ITZ 65 mg, and SUBA-ITZ 50 mg-in superficial dermatophytosis.

Methods: In this open-label, randomised study at a tertiary hospital, 150 patients with confirmed tinea corporis, cruris, or faciei were equally assigned to: Group A: C-ITZ 100 mg BID Group B: SUBA-ITZ 65 mg BID Group C: SUBA-ITZ 50 mg BID Treatment lasted 6 weeks without topical antifungals. Assessments were done at 3 and 6 weeks; relapse and recurrence were monitored telephonically at 3 and 6 months.

Results: All groups showed similar clinical response at 6 weeks (BSA, PGA, KOH negativity), with no significant differences. At 3 months, Group C had significantly lower relapse and recurrence (10.2%) than Group B (31.1%, 28.9%) and Group A (23.9%, 26.1%) (p < 0.05). By 6 months, differences were not significant.

Conclusion: All three itraconazole formulations demonstrated comparable short-term efficacy in treating superficial dermatophytosis. These findings underscore the need for larger, long-term randomised controlled trials to optimise itraconazole dosing strategies.

在印度,皮肤真菌病是一种慢性公共卫生问题,通常需要全身抗真菌药物。伊曲康唑(Itraconazole, ITZ)是常用的,但传统形式的吸收变化较大。超生物可利用伊曲康唑(SUBA-ITZ)提供了改善的药代动力学,尽管临床比较有限。目的:比较常规ITZ 100 mg (C-ITZ)、SUBA-ITZ 65 mg、SUBA-ITZ 50 mg三种口服ITZ制剂治疗浅表性皮肤癣的疗效、安全性、复发率和复发率。方法:在一所三级医院进行的这项开放标签随机研究中,150名确诊为体癣、皮疹或面部癣的患者被平均分配到:a组:C- itz 100 mg BID B组:SUBA-ITZ 65 mg BID C组:SUBA-ITZ 50 mg BID治疗持续6周,不使用局部抗真菌药物。在第3周和第6周进行评估;在3个月和6个月时电话监测复发和复发情况。结果:6周时各组临床反应相似(BSA、PGA、KOH阴性),差异无统计学意义。3个月时,C组的复发和复发率(10.2%)明显低于B组(31.1%,28.9%)和A组(23.9%,26.1%)。(p)结论:三种伊曲康唑制剂治疗浅表性皮肤癣的短期疗效相当。这些发现强调需要更大规模的长期随机对照试验来优化伊曲康唑的给药策略。
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引用次数: 0
Central Nervous System Histoplasmosis: A Retrospective Review of Clinical Characteristics, Treatments and Outcomes With Comparison to Disseminated Histoplasmosis Without Central Nervous System Involvement. 中枢神经系统组织胞浆菌病:临床特征、治疗方法和与未累及中枢神经系统的播散性组织胞浆菌病比较的结果的回顾性回顾。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70068
Tyler J Brehm, Kristen A Staggers, Richard J Hamill, Rodrigo Hasbun, Hana M El Sahly

Background: Central nervous system (CNS) histoplasmosis occurs in 5%-10% of patients with disseminated histoplasmosis, is sparsely described in the literature and is highly morbid.

Objectives: To evaluate clinical characteristics and outcomes of patients with CNS and non-CNS disseminated histoplasmosis.

Methods: In this retrospective case-control study, we matched 45 cases of CNS histoplasmosis with 45 controls with disseminated histoplasmosis without CNS involvement by hospital and date of encounter. Data were collected from three hospitals from January 2000 to December 2022 using histoplasmosis-related ICD-9/10 codes. Patients were classified as confirmed (Histoplasma growth on cerebrospinal fluid [CSF] or CNS culture), probable (positive CSF Histoplasma antigen or antibody), or possible (positive urine or serum Histoplasma antigen plus either CSF WBC ≥ 5 cells/μL or abnormalities on CNS imaging, with no other evident cause) CNS histoplasmosis.

Results: CNS (n = 45) and non-CNS disseminated histoplasmosis (n = 45) patients had similar demographic and clinical characteristics, although persons living with HIV (PLWH) were more prevalent in the CNS histoplasmosis group (93.3% and 80.0%, respectively, p = 0.019). CSF profiles (CSF WBC, glucose and total protein) and MRI brain imaging were normal in 28.2% and 21.9% of CNS histoplasmosis patients, respectively. CNS histoplasmosis patients were severely ill, with 34.1% requiring ICU care and Glasgow Outcome Scores of 1-4 in 51.1% of patients at discharge. In-hospital mortality was 6.7% for CNS vs. 13.3% for disseminated histoplasmosis (p = 0.215).

Conclusions: In this large CNS histoplasmosis cohort, we found an increased prevalence of PLWH in CNS vs. non-CNS disseminated histoplasmosis. Similar to prior CNS histoplasmosis cohorts, we report relatively high rates of normal CSF profiles (28.2%) and MRI brain imaging (21.9%). We also found significant morbidity in patients with CNS histoplasmosis, data which were not reported in prior cohorts.

背景:中枢神经系统(CNS)组织胞浆菌病发生在弥散性组织胞浆菌病患者的5%-10%,文献中很少描述,发病率很高。目的:评价中枢神经系统和非中枢神经系统弥散性组织浆菌病患者的临床特点和预后。方法:在本回顾性病例对照研究中,我们将45例中枢神经系统组织胞浆菌病与45例未累及中枢神经系统的弥散性组织胞浆菌病按医院和发病日期进行匹配。使用组织浆菌病相关ICD-9/10代码从2000年1月至2022年12月收集了三家医院的数据。将患者分为确诊(脑脊液(CSF)或中枢神经系统培养的组织浆体生长)、可能(脑脊液组织浆体抗原或抗体阳性)或可能(尿液或血清组织浆体抗原阳性且脑脊液WBC≥5个细胞/μL或中枢神经系统影像学异常,无其他明显原因)中枢神经系统组织浆体病。结果:中枢神经系统(n = 45)和非中枢神经系统弥散性组织胞浆菌病(n = 45)患者具有相似的人口统计学和临床特征,尽管艾滋病毒感染者(PLWH)在中枢神经系统组织胞浆菌病组更为普遍(分别为93.3%和80.0%,p = 0.019)。28.2%和21.9%的中枢神经系统组织浆菌病患者脑脊液谱(脑脊液白细胞、葡萄糖和总蛋白)和MRI脑成像正常。中枢神经系统组织胞浆菌病患者病情严重,34.1%的患者需要ICU护理,51.1%的患者出院时格拉斯哥预后评分为1-4。中枢神经系统疾病的住院死亡率为6.7%,弥散性组织胞浆菌病为13.3% (p = 0.215)。结论:在这个大型中枢神经系统组织浆菌病队列中,我们发现中枢神经系统中PLWH的患病率高于非中枢神经系统弥散性组织浆菌病。与之前的中枢神经系统组织浆菌病队列相似,我们报告了相对较高的脑脊液正常发生率(28.2%)和MRI脑成像(21.9%)。我们还发现中枢神经系统组织浆菌病患者有显著的发病率,这些数据在以前的队列中没有报道。
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引用次数: 0
Performance Evaluation of Five Real-Time PCR Assays for the Detection of Candida auris DNA. 五种实时荧光定量PCR检测耳念珠菌DNA的性能评价。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70065
Jochem B Buil, Bart van den Bosch, Suzan J van der Maas, Eelco F J Meijer, Theun de Groot, Joseph Meletiadis, Paul E Verweij, Willem J G Melchers, Suzan D Pas

Objectives: This study aimed to systematically evaluate and compare the performance of two laboratory-developed assays (LDAs) and three commercially available real-time PCR assays for the detection of Candida auris. The analytical sensitivity, specificity and limit of detection (LOD) of each assay were assessed, alongside their clinical sensitivity in identifying C. auris colonisation.

Methods: Ten C. auris strains representing five clades, as well as genetically related yeasts, common yeast species, and dermatophytes, were used to assess assay sensitivity and cross reactivity. Clinical and environmental samples were collected from patients during an outbreak and tested with three commercial PCR assays (AurisID, Fungiplex, FungiXpert) and two LDAs (CDC LDA, EMC LDA). LOD was determined using Probit analysis. Diagnostic sensitivity was evaluated by comparing the detection rate of each individual assay to the total detection rate of all assays combined.

Results: The EMC LDA exhibited the highest analytical sensitivity, with a LOD of 8 conidia/reaction, followed by CDC LDA (16 conidia/reaction), AurisID and FungiXpert (19 conidia/reaction), and Fungiplex (596 conidia/reaction). Specificity testing revealed cross-reactivity in the CDC LDA and AurisID assays with C. pseudohaemulonii at high conidia levels, while no cross-reactivity was observed in the other assays. EMC LDA showed the highest clinical sensitivity (100%), whereas Fungiplex had the lowest positivity rate (71%). No false positives were observed in negative control swabs for any assay.

Conclusions: Real-time PCR is a crucial tool for the rapid and sensitive detection of C. auris , especially in clinical settings where timely identification is essential for effective patient management and infection control. Numerous PCR assays are available for this purpose; however, our study demonstrates that the sensitivity of these assays can vary significantly. The observed differences underscore the importance of establishing international reference standards and proficiency panels to enhance the accuracy and comparability of assay performance across different studies and laboratories.

目的:本研究旨在系统地评价和比较两种实验室开发的检测方法(lda)和三种市售实时PCR检测方法检测念珠菌的性能。评估了每种检测方法的分析灵敏度、特异性和检出限(LOD),以及它们在鉴定耳念珠菌定殖方面的临床敏感性。方法:采用代表5个分支的10株金黄色葡萄球菌,以及遗传相关酵母菌、常见酵母菌和皮肤真菌,评估检测灵敏度和交叉反应性。在疫情期间从患者身上收集临床和环境样本,并使用三种商用PCR检测方法(AurisID、Fungiplex、FungiXpert)和两种LDA (CDC LDA、EMC LDA)进行检测。LOD采用Probit分析法测定。通过比较每个单独检测的检出率与所有检测的总检出率来评估诊断敏感性。结果:EMC LDA的分析灵敏度最高,LOD为8个分生菌/反应,其次为CDC LDA(16个分生菌/反应)、AurisID和FungiXpert(19个分生菌/反应)和Fungiplex(596个分生菌/反应)。特异性测试显示CDC LDA和AurisID检测与高分生孢子水平的假马龙假梭菌具有交叉反应性,而其他检测未观察到交叉反应性。EMC LDA临床敏感性最高(100%),而Fungiplex阳性率最低(71%)。阴性对照拭子在任何检测中均未观察到假阳性。结论:实时荧光定量PCR是快速、灵敏检测金黄色葡萄球菌的重要工具,特别是在临床环境中,及时识别对有效的患者管理和感染控制至关重要。许多PCR检测可用于此目的;然而,我们的研究表明,这些检测方法的敏感性可能会有很大差异。观察到的差异强调了建立国际参考标准和熟练度小组以提高不同研究和实验室测定性能的准确性和可比性的重要性。
{"title":"Performance Evaluation of Five Real-Time PCR Assays for the Detection of Candida auris DNA.","authors":"Jochem B Buil, Bart van den Bosch, Suzan J van der Maas, Eelco F J Meijer, Theun de Groot, Joseph Meletiadis, Paul E Verweij, Willem J G Melchers, Suzan D Pas","doi":"10.1111/myc.70065","DOIUrl":"https://doi.org/10.1111/myc.70065","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to systematically evaluate and compare the performance of two laboratory-developed assays (LDAs) and three commercially available real-time PCR assays for the detection of Candida auris. The analytical sensitivity, specificity and limit of detection (LOD) of each assay were assessed, alongside their clinical sensitivity in identifying C. auris colonisation.</p><p><strong>Methods: </strong>Ten C. auris strains representing five clades, as well as genetically related yeasts, common yeast species, and dermatophytes, were used to assess assay sensitivity and cross reactivity. Clinical and environmental samples were collected from patients during an outbreak and tested with three commercial PCR assays (AurisID, Fungiplex, FungiXpert) and two LDAs (CDC LDA, EMC LDA). LOD was determined using Probit analysis. Diagnostic sensitivity was evaluated by comparing the detection rate of each individual assay to the total detection rate of all assays combined.</p><p><strong>Results: </strong>The EMC LDA exhibited the highest analytical sensitivity, with a LOD of 8 conidia/reaction, followed by CDC LDA (16 conidia/reaction), AurisID and FungiXpert (19 conidia/reaction), and Fungiplex (596 conidia/reaction). Specificity testing revealed cross-reactivity in the CDC LDA and AurisID assays with C. pseudohaemulonii at high conidia levels, while no cross-reactivity was observed in the other assays. EMC LDA showed the highest clinical sensitivity (100%), whereas Fungiplex had the lowest positivity rate (71%). No false positives were observed in negative control swabs for any assay.</p><p><strong>Conclusions: </strong>Real-time PCR is a crucial tool for the rapid and sensitive detection of C. auris , especially in clinical settings where timely identification is essential for effective patient management and infection control. Numerous PCR assays are available for this purpose; however, our study demonstrates that the sensitivity of these assays can vary significantly. The observed differences underscore the importance of establishing international reference standards and proficiency panels to enhance the accuracy and comparability of assay performance across different studies and laboratories.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"68 5","pages":"e70065"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
β-D-Glucan Testing in Candidemia: Determinants of Positivity and Association With Mortality. 念珠菌β- d -葡聚糖检测:阳性决定因素及其与死亡率的关系。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70067
Karl Oldberg, Jakob Stenmark, Helena Hammarström

Background: Serum 1,3-β-d-glucan (BDG) tests are frequently used for diagnosing invasive candidiasis. However, BDG tests remain negative in many patients with candidemia, and factors influencing the probability for positive test results are poorly understood.

Objectives: To study clinical and microbiological factors predictive of a positive BDG test, as well as the association of a positive BDG test with mortality in patients with candidemia.

Methods: In a retrospective cohort of patients with candidemia, BDG was analysed by the Glucatell assay and the Wako Beta-Glucan Test. Predisposing conditions, focus of infection and other variables were retrieved from medical charts and laboratory databases. Their association with a positive BDG test, and the association between positive BDG and death was tested in univariate analysis and multivariable logistic regression.

Results: We included 134 patients with candidemia. Positive BDG and a non-abdominal deep-seated focus of infection (e.g., hematogenously disseminated infection and deep mediastinal/pleural candidiasis) were positively correlated in univariate and multivariable analyses [Wako adjusted odds ratio 9.11 (95% CI 1.66-172, p = 0.039), Glucatell adjOR 9.14 (95% CI 1.66-172, p = 0.039)]. Having a positive BDG test increased the risk for 90 days mortality after controlling for potential confounders, mainly age, septic shock, and ICU admission [Wako adjOR 4.73 (95% CI 1.71-14.7, p = 0.0043), Glucatell adjOR 3.59 (95% CI 1.33-10.6, p = 0.015)].

Conclusions: In patients with candidemia, a positive BDG test is more common in the presence of a concomitant non-abdominal deep-seated infection. Patients with a positive BDG test have a higher 90-day mortality.

背景:血清1,3-β-d-葡聚糖(BDG)检测常用于诊断侵袭性念珠菌病。然而,在许多念珠菌病患者中,BDG检测仍为阴性,而影响检测结果阳性概率的因素尚不清楚。目的:研究预测BDG检测阳性的临床和微生物因素,以及BDG检测阳性与念珠菌病患者死亡率的关系。方法:对念珠菌血症患者进行回顾性队列分析,采用Glucatell试验和Wako β -葡聚糖试验分析BDG。从医学图表和实验室数据库中检索易感条件、感染焦点和其他变量。用单因素分析和多因素logistic回归检验了它们与BDG阳性的相关性,以及BDG阳性与死亡的相关性。结果:我们纳入134例念珠菌病患者。在单因素和多因素分析中,BDG阳性与非腹部深部感染灶(如血源性弥散性感染和深纵隔/胸膜念珠菌病)呈正相关[Wako校正比值比为9.11 (95% CI 1.66-172, p = 0.039), Glucatell adjOR为9.14 (95% CI 1.66-172, p = 0.039)]。在控制了潜在混杂因素(主要是年龄、感染性休克和ICU入院)后,BDG检测阳性增加了90天死亡率的风险[Wako值4.73 (95% CI 1.71-14.7, p = 0.0043), Glucatell值3.59 (95% CI 1.33-10.6, p = 0.015)]。结论:在念珠菌病患者中,伴有非腹腔深部感染的BDG检测阳性更为常见。BDG检测阳性的患者90天死亡率较高。
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引用次数: 0
Common Disease-Difficult Understanding: Readability Analysis of Superficial Skin Fungal Infections On-Line Materials in European Languages. 常见病-难以理解:浅表皮肤真菌感染的可读性分析。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70057
Tomasz Skrzypczak, Anna Skrzypczak, Andrzej Jaworek, Jacek C Szepietowski

Background: Studies analysing the readability of online materials about dermatomycoses were very limited.

Objectives: This study evaluated the readability of online materials related to superficial skin fungal infections in English, German, French, Italian, Spanish and Polish.

Methods: The terms 'dermatomycosis', 'dermatophytosis' and 'trichophytosis' translated into included languages were searched using the Google search engine. The first 50 records in each language were screened for suitability. Articles that were accessible, relevant to dermatological fungal infections and aimed at patient education were included. The LIX score was utilised to assess readability.

Results: In general, 167 articles out of 900 screened (19%) were analysed. The overall mean LIX score was 56 ± 7, which classified articles as very difficult to comprehend. The most readable were articles retrieved with the search term 'trichophytosis' with a mean LIX score of 49 ± 3, followed by 'dermatophytosis' with 54 ± 8 and 'dermatomycosis' with 58 ± 7 (p < 0.001). The most readable articles were in English (48 ± 7) and Spanish (50 ± 5), followed by German (54 ± 4), French (55 ± 6), Italian (59 ± 5) and Polish (63 ± 4) (p < 0.001). The increase in the number of analysed articles was correlated with a higher average LIX score (p = 0.036, R2 = 0.708).

Conclusions: Low availability and readability of online patient materials related to superficial skin fungal infections could hinder patient understanding, leading to improper antifungal use, increased recurrence rates and the risk of antifungal resistance. The dermatologists should take action to ensure adequate online materials in Internet-based society.

背景:分析皮肤真菌病在线资料可读性的研究非常有限。目的:本研究评估了英语、德语、法语、意大利语、西班牙语和波兰语中与皮肤表层真菌感染相关的在线资料的可读性。方法:使用谷歌搜索引擎搜索翻译成所纳入语言的术语“皮肤真菌病”、“皮肤癣”和“毛癣”。对每种语言的前50条记录进行了筛选以确定其适用性。文章是可访问的,相关的皮肤病真菌感染和旨在患者教育纳入。LIX评分用于评估可读性。结果:总的来说,900篇筛选的文献中有167篇(19%)被分析。总体平均LIX得分为56±7,这将文章归类为非常难以理解。以“毛癣”为检索词的文章可读性最高,LIX平均评分为49±3分,其次是“皮肤癣”,54±8分,“皮肤真菌病”,58±7分(p 2 = 0.708)。结论:与浅表皮肤真菌感染相关的在线患者资料的可获得性和可读性较低,可能会阻碍患者的理解,导致抗真菌药物使用不当,增加复发率和抗真菌药物耐药的风险。皮肤科医生应采取行动,以确保在互联网为基础的社会有足够的网上资料。
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引用次数: 0
Efficacy and Safety of Efinaconazole 10% Topical Solution for Treatment of Onychomycosis in Older Adults: A Post Hoc Analysis of Two Phase 3 Randomised Trials. 10%艾非那康唑局部溶液治疗老年人甲真菌病的疗效和安全性:两项3期随机试验的事后分析
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70069
Shari R Lipner, Aditya K Gupta, Warren S Joseph, Boni Elewski, Eric Guenin, Tracey C Vlahovic

Background: Onychomycosis is common in older adults and can be difficult to treat owing to slower nail growth, increased nail thickness, comorbidities, and concomitant medications. Oral treatments can be complicated by contraindications, drug-drug interactions, and adverse effects. Topical treatments such as efinaconazole 10% solution may be beneficial for treating older adults.

Objectives: To evaluate the efficacy/safety of efinaconazole 10% solution in adults aged ≥ 65 years with toenail onychomycosis.

Patients/methods: In two multicenter, double-blind, phase 3 studies (NCT01008033; NCT01007708), patients with mild to moderate toenail onychomycosis were randomised (3:1) to once-daily efinaconazole or vehicle for 48 weeks, with a 4-week follow-up. Pooled data for participants aged ≥ 65 years were analysed post hoc (n = 162 efinaconazole, n = 56 vehicle). The primary endpoint was complete cure (0% involvement of target toenail plus mycologic cure [negative KOH and fungal culture]) at week 52. Treatment-emergent adverse events (TEAEs) were assessed throughout.

Results: At week 52, a significantly greater proportion of older adults (aged 65-71 years) achieved complete cure with efinaconazole than vehicle (13.6% vs. 3.6%; p < 0.05). Complete/almost complete cure rate was also significantly greater (≤ 5% involvement and mycologic cure; 19.1% vs. 5.4%; p = 0.01), and over half (59.2%) of participants achieved mycologic cure with efinaconazole versus 12.5% with vehicle (p < 0.001). Treatment-related TEAE rates with efinaconazole were low (6.0%) and similar to the overall study population.

Conclusions: Efinaconazole 10% solution showed similar efficacy/safety in participants aged ≥ 65 years to the overall phase 3 population, despite potential age-related nail changes. These results demonstrate the benefits of efinaconazole in older patients with onychomycosis.

背景:甲真菌病常见于老年人,由于指甲生长缓慢,指甲厚度增加,合并症和伴随药物治疗,可能难以治疗。口服治疗可能因禁忌症、药物-药物相互作用和不良反应而复杂化。局部治疗如10%艾非那康唑溶液可能对治疗老年人有益。目的:评价10%艾非那康唑溶液治疗≥65岁成人甲真菌病的疗效和安全性。患者/方法:两项多中心、双盲、3期研究(NCT01008033;NCT01007708),轻度至中度脚趾甲真菌病患者随机(3:1)分到每日一次的依非那康唑组或对照组,为期48周,随访4周。对年龄≥65岁参与者的汇总数据进行事后分析(n = 162, n = 56)。主要终点是在第52周完全治愈(目标趾甲0%受累加上真菌学治愈[KOH阴性和真菌培养])。在整个过程中评估治疗中出现的不良事件(teae)。结果:在第52周,老年人(65-71岁)完全治愈的比例明显高于对照组(13.6% vs 3.6%;p结论:10%艾非那康唑溶液在年龄≥65岁的受试者中表现出与总体3期人群相似的疗效/安全性,尽管可能出现与年龄相关的指甲变化。这些结果证明了艾非那康唑对老年甲癣患者的益处。
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引用次数: 0
Retrospective Review of Fungal Keratitis at Two Tertiary Hospitals in Perth, Western Australia Between 2006 and 2022. 2006年至2022年西澳大利亚珀斯两家三级医院真菌性角膜炎的回顾性分析
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70071
Harry Hohnen, Nishant Davidoss, Steven Wiffen, Arron Radinger, Shu Jin Tan, Dianne Gardam, Andrea Ang

Background: Fungal keratitis is a significant cause of ocular morbidity globally. There is a lack of contemporary local data in Western Australia.

Methods: A retrospective chart review of fungal keratitis cases at two tertiary hospitals in Perth, Western Australia identified between 1 January 2006 and 31 December 2022. Data on patient demographics, isolated organisms, risk factors, clinical features, outcomes, and management were collected and analysed.

Results: There were 68 cases of clinically significant fungal keratitis with positive culture results from corneal scrapes. The most commonly isolated pathogens were Fusarium species (37%), Candida species (28%), Scedosporium species (10%), and Aspergillus species (9%). The most common predisposing risk factors were prior use of topical corticosteroids (40%), contact lens wear (35%), ocular surface disease (without a corneal graft) (25%), ocular trauma (including organic matter exposure) (18%), and a previous corneal graft procedure (16%). Corneal perforation occurred in 25% of cases. A high proportion, 22 episodes in 18 eyes (26%), of patients required therapeutic penetrating keratoplasty, and 6% required evisceration.

Conclusions: Results were largely consistent with previous studies in the Australian context. Fusarium species and Candida albicans were the most common pathogens isolated. Prior topical corticosteroid use was the most common predisposing risk factor, followed closely by contact lens wear and ocular surface disease. A large proportion of patients experienced corneal perforations and required penetrating keratoplasty.

背景:真菌性角膜炎是全球眼部发病的重要原因。西澳大利亚缺乏当代当地数据。方法:对2006年1月1日至2022年12月31日在西澳大利亚珀斯的两家三级医院发现的真菌性角膜炎病例进行回顾性分析。收集和分析了患者人口统计学、分离微生物、危险因素、临床特征、结局和管理方面的数据。结果:有临床意义的真菌性角膜炎68例,培养结果阳性。最常见的病原菌是镰刀菌(37%)、念珠菌(28%)、塞多孢子菌(10%)和曲霉(9%)。最常见的易感危险因素是既往使用局部皮质类固醇(40%)、佩戴隐形眼镜(35%)、眼表疾病(未接受角膜移植)(25%)、眼外伤(包括接触有机物)(18%)和既往角膜移植手术(16%)。25%的病例发生角膜穿孔。18只眼睛22次(26%)的患者需要治疗性穿透性角膜移植术,6%需要摘除角膜。结论:结果在很大程度上与澳大利亚背景下的先前研究一致。镰刀菌和白色念珠菌是最常见的病原菌。既往局部使用皮质类固醇是最常见的易感危险因素,其次是隐形眼镜佩戴和眼表疾病。大部分患者出现角膜穿孔,需要进行穿透性角膜移植术。
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引用次数: 0
Candida vulturna, the Next Fungal Menace? A Narrative Review. 秃鹫假丝酵母,下一个真菌威胁?叙述性评论。
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70070
Ritika Harchand, Bram Spruijtenburg, Eelco F J Meijer, Theun de Groot, Shivaprakash M Rudramurthy, Jacques F Meis

Introduction: The yeast Candida vulturna is a member of the Candida haemulonii species complex, like its close relative Candida auris. Members of this species complex, including C. vulturna, often display reduced susceptibility to one or more antifungal classes. Human invasive infections by C. vulturna are increasingly reported in various countries, while the first identification of this fungus, isolated from a flower, occurred less than 10 years ago. The purpose of this review is to compile all reported outbreaks and cases and describe the characteristics of this emerging yeast.

Methods: PubMed, Scopus, Web of Science and Google Scholar were reviewed for publications until April 14, 2025. Records in English were found by using the keyword Candida (Candidozyma) vulturna, and were included if cases were invasive infections.

Results: All reported 94 cases were exclusively from the last 10 years, often in Asian or Latin American countries and included three outbreaks in Brazil, Vietnam and China. Patients displayed diverse clinical characteristics with an overall low mortality rate of 18%. Most studies (n = 11) performed antifungal susceptibility testing (AFST) with microbroth dilution methods and found reduced susceptibility to azoles and amphotericin B. The ERG11P135S mutation was shown to confer azole resistance, although the mechanism behind amphotericin B resistance has not been uncovered. Identification by MALDI-ToF routinely misidentified C. vulturna as C. pseudohaemulonii or C. duobushaemulonii, leaving molecular identification by ITS sequencing or whole genome sequencing as the only available methods for accurate species determination.

Conclusion: Although C. vulturna is still a rare yeast, cases are increasingly reported in tropical regions. The yeast has outbreak potential, in addition to reduced susceptibility to azoles and amphotericin B. Treatment with echinocandins showed favourable outcomes with a low mortality rate.

简介:秃鹫念珠菌是念珠菌haemulonii种复合体的成员,与其近亲耳念珠菌一样。该物种复合体的成员,包括秃鹫,通常表现出对一种或多种抗真菌类的敏感性降低。vulturna对人类的侵袭性感染在各个国家都有越来越多的报道,而这种真菌的首次鉴定是在不到10年前从一朵花中分离出来的。本综述的目的是汇编所有报道的暴发和病例,并描述这种新兴酵母的特征。方法:检索PubMed、Scopus、Web of Science和b谷歌Scholar,检索截止到2025年4月14日的出版物。用关键词vulturna念珠菌(Candidozyma)查找英文记录,并纳入侵袭性感染病例。结果:所有报告的94例病例均发生在过去10年,通常发生在亚洲或拉丁美洲国家,其中包括巴西、越南和中国的三次暴发。患者表现出多样化的临床特征,总体死亡率低至18%。大多数研究(n = 11)采用微肉汤稀释法进行了抗真菌药敏试验(AFST),发现对唑类药物和两性霉素B的敏感性降低。尽管两性霉素B耐药的机制尚未揭示,但ERG11P135S突变可导致唑类药物耐药。MALDI-ToF鉴定通常会将C. vulturna错认为C. pseudohaemulonii或C. duobushaemulonii,从而使ITS测序或全基因组测序的分子鉴定成为准确确定物种的唯一方法。结论:虽然秃鹫酵母仍然是一种罕见的酵母菌,但热带地区的病例报道越来越多。除了降低对唑类和两性霉素b的敏感性外,这种酵母还具有爆发的潜力。用刺白菌素治疗显示出良好的结果,死亡率低。
{"title":"Candida vulturna, the Next Fungal Menace? A Narrative Review.","authors":"Ritika Harchand, Bram Spruijtenburg, Eelco F J Meijer, Theun de Groot, Shivaprakash M Rudramurthy, Jacques F Meis","doi":"10.1111/myc.70070","DOIUrl":"10.1111/myc.70070","url":null,"abstract":"<p><strong>Introduction: </strong>The yeast Candida vulturna is a member of the Candida haemulonii species complex, like its close relative Candida auris. Members of this species complex, including C. vulturna, often display reduced susceptibility to one or more antifungal classes. Human invasive infections by C. vulturna are increasingly reported in various countries, while the first identification of this fungus, isolated from a flower, occurred less than 10 years ago. The purpose of this review is to compile all reported outbreaks and cases and describe the characteristics of this emerging yeast.</p><p><strong>Methods: </strong>PubMed, Scopus, Web of Science and Google Scholar were reviewed for publications until April 14, 2025. Records in English were found by using the keyword Candida (Candidozyma) vulturna, and were included if cases were invasive infections.</p><p><strong>Results: </strong>All reported 94 cases were exclusively from the last 10 years, often in Asian or Latin American countries and included three outbreaks in Brazil, Vietnam and China. Patients displayed diverse clinical characteristics with an overall low mortality rate of 18%. Most studies (n = 11) performed antifungal susceptibility testing (AFST) with microbroth dilution methods and found reduced susceptibility to azoles and amphotericin B. The ERG11<sup>P135S</sup> mutation was shown to confer azole resistance, although the mechanism behind amphotericin B resistance has not been uncovered. Identification by MALDI-ToF routinely misidentified C. vulturna as C. pseudohaemulonii or C. duobushaemulonii, leaving molecular identification by ITS sequencing or whole genome sequencing as the only available methods for accurate species determination.</p><p><strong>Conclusion: </strong>Although C. vulturna is still a rare yeast, cases are increasingly reported in tropical regions. The yeast has outbreak potential, in addition to reduced susceptibility to azoles and amphotericin B. Treatment with echinocandins showed favourable outcomes with a low mortality rate.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"68 5","pages":"e70070"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genotypic Diversity and Molecular Basis of Fluconazole Resistance in Candida parapsilosis Clinical Isolates Collected Over 7 Years in a Tertiary-Care Hospital in North India. 印度北部一家三级医院7年来收集的假丝酵母菌临床分离株氟康唑耐药的基因型多样性和分子基础
IF 4.1 2区 医学 Q1 DERMATOLOGY Pub Date : 2025-05-01 DOI: 10.1111/myc.70062
Vrinda Sharma, Sourav Das, Bram Spruijtenburg, Theun de Groot, Eelco Meijer, Harsimran Kaur, Shivaprakash M Rudramurthy, Anup Ghosh

Background: The recent rise in the global incidence of fluconazole resistance in C. parapsilosis has become a significant public health concern. Epidemiological studies suggest that fluconazole resistance in C. parapsilosis spreads through endemic clones. We, therefore, investigated the molecular epidemiology of fluconazole-resistant C. parapsilosis in our centre.

Methods: C. parapsilosis isolates from 2016 through 2022 were investigated for antifungal susceptibility. Fluconazole-resistant isolates were analysed for ERG11 mutation using Sanger sequencing. Gene expression profiles of ERG11, CDR1 and MDR1 were assessed by real-time qPCR. The epidemiological relationship of resistant and susceptible isolates of C. parapsilosis was investigated using short tandem repeat typing. Additionally, biofilm production and cell wall ergosterol contents were also quantified and compared.

Results: Among 572 C. parapsilosis isolates, 48 (8.4%) were resistant to fluconazole. Of 28 recoverable resistant isolates, 17.9% (5/28) were wild-type and 82.1% (23/28) harboured the following ERG11 mutations: Y132F (n = 3), K143R (n = 10) and K143R + R398I (10/28). Significant fold-changes were observed in ERG11 (p = 0.037) and MDR1 (p = 0.008) gene expressions in fluconazole resistant compared to susceptible isolates. Contrary to global reports, STR typing suggested a limited clonal transmission of resistant C. parapsilosis with multiple introductions of resistant isolates in our centre. On fluconazole exposure, ergosterol content significantly increased (p < 0.01) in resistant isolates, particularly in isolates harbouring ERG11K143R + R398I mutations. In contrast, fluconazole-susceptible isolates formed comparatively higher baseline biofilm (p < 0.05) than resistant isolates with ERG11K143R mutation.

Conclusion: The current study underscores the need for continuous molecular surveillance and tailored therapeutic options for effective management of fluconazole resistance in C. parapsilosis.

背景:最近全球氟康唑耐药C. parapsilosis的发病率上升已成为一个重要的公共卫生问题。流行病学研究表明,弓形虫对氟康唑的耐药性通过地方性克隆传播。因此,我们在本中心调查了氟康唑耐药的弓形虫的分子流行病学。方法:对2016 ~ 2022年分离的假丝裂菌进行抗真菌药敏试验。采用Sanger测序对耐氟康唑分离株进行ERG11突变分析。实时荧光定量pcr检测ERG11、CDR1和MDR1基因表达谱。采用短串联重复分型方法,研究了耐药株和敏感株间的流行病学关系。此外,还定量比较了生物膜产量和细胞壁麦角甾醇含量。结果:572株株中,48株(8.4%)对氟康唑耐药。在28株可恢复耐药菌株中,17.9%(5/28)为野生型,82.1%(23/28)携带以下ERG11突变:Y132F (n = 3)、K143R (n = 10)和K143R + R398I(10/28)。氟康唑耐药菌株的ERG11 (p = 0.037)和MDR1 (p = 0.008)基因表达明显改变。与全球报告相反,STR分型表明,在我们的中心,通过多次引入耐药分离株,耐药C. parapsilosis发生了有限的克隆传播。氟康唑暴露后,麦角甾醇含量显著增加(p K143R + R398I突变)。相比之下,氟康唑敏感的分离株形成了相对较高的基线生物膜(p K143R突变)。结论:目前的研究强调需要持续的分子监测和量身定制的治疗方案,以有效管理氟康唑耐药性。
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引用次数: 0
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