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Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital 由念珠菌和非念珠菌罕见酵母菌引起的真菌血症的比较:一家三级医院的回顾性研究
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-15 DOI: 10.1093/mmy/myae037
Yasemin Oz, Mustafa Yılmaz, Tuba Bulduk, Mehmet Basayigit, Eren Gunduz, Selma Metintas
Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor and outcome. In addition, a candidemia group including the patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to reference method. A total of 85 patients with fungemia episodes were included; 25 with NCY fungemia, 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole and amphotericin B were ≤ 2 µg/ml and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species were the problem particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.
虽然念珠菌是真菌病最常见的致病菌,但世界各地关于非念珠菌罕见酵母菌(NCY)的报道也越来越多。虽然这些酵母菌感染的重要性已得到认可,但目前关于这些病原体的流行病学信息却很有限,而且它们对抗真菌的敏感性也各不相同。在本研究中,我们旨在通过与念珠菌血症进行比较,评估由 NCY 引起的真菌血症的临床特征。我们对 2011 年 1 月至 2023 年 8 月期间发生的 NCY 真菌血症的临床特征、诱发因素和结果进行了回顾性评估。此外,还对同期的念珠菌血症患者进行了分组比较。抗真菌药敏试验按照参考方法进行。共纳入 85 例真菌血症患者,其中 25 例为 NCY 真菌血症,60 例为念珠菌血症。氟康唑对几乎所有 NCY 分离物的最小抑菌浓度(MIC)值都很高。伏立康唑、泊沙康唑和两性霉素 B 的 MIC 值≤ 2 µg/ml,卡泊芬净和阿尼芬净对大多数分离菌株的 MIC 值≥ 1 µg/ml。血液恶性肿瘤、免疫抑制治疗、中性粒细胞减少和长期中性粒细胞减少、多微生物菌血症/真菌血症、预先接触抗真菌药物和突破性真菌血症与NCY真菌血症有关,而重症监护病房入院、糖尿病、导尿管和全肠外营养则与念珠菌血症有关。总之,大多数真菌血症都是由NCY菌引起的,尤其是在血液科和血液恶性肿瘤患者中。三度接触抗真菌药物可能会导致真菌血症的流行病学发生变化,从而有利于非阿氏念珠菌和/或NCY。
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引用次数: 0
Evaluation of Interleukin-8 Levels in the Diagnosis of Invasive Pulmonary Aspergillosis in Patients With Haematological Malignancies 评估白细胞介素-8 水平在诊断血液恶性肿瘤患者侵袭性肺曲霉菌病中的作用
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-09 DOI: 10.1093/mmy/myae036
Levent Şensoy, Aynur Atilla, Yusuf Taha Güllü, Demet Gür Vural, Mehmet Turgut, Şaban Esen, Esra Tanyel
This study aimed to determine the level of IL-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, hematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84±15.38 years, while that of the controls was 58.38±16.64 years. Of the patients, 2/25 were classified as having “proven,” 13/25 as “probable,” and 10/25 as “possible” invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cut-off value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/L, sensitivity was 72%, specificity was 64%, PPV was 50%, and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.
本研究旨在确定 IL-8 在诊断侵袭性肺曲霉菌病(IPA)中的水平。我们对 50 名对照组和 25 名患有血液恶性肿瘤的 IPA 患者进行了研究。我们对患者的人口统计学数据、血液学诊断、化疗方案、半乳糖甘露聚糖水平、真菌培养和计算机断层扫描结果进行了前瞻性评估。采用 ELISA 方法对 IL-8 水平进行了研究。病例组患者的平均年龄为(60.84±15.38)岁,对照组患者的平均年龄为(58.38±16.64)岁。其中,2/25 的患者被归类为 "已证实",13/25 的患者被归类为 "可能",10/25 的患者被归类为 "可能 "侵袭性曲霉菌病(IA)。与对照组相比,病例组的血清 IL-8 水平明显较高。血清IL-8水平与中性粒细胞计数呈负相关,与中性粒细胞减少的持续时间呈正相关。检测IPA疾病的血清IL-8参数的重要临界值为≥274纳克/升,敏感性为72%,特异性为64%,PPV为50%,NPV为82%。在亚组分析中,病例组与中性粒细胞减少对照组患者的血清 IL-8 水平无显著差异,而与非中性粒细胞减少对照组患者有显著差异。患 IPA 的中性粒细胞增多症患者的血清 IL-8 水平不足以诊断疾病和预测死亡率。我们仍然需要新的、易于应用的、具有高敏感性和特异性的方法来诊断IPA。
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引用次数: 0
Comparison of Candida colonization in intensive care unit patients with and without COVID-19: First prospective cohort study from Turkey 有 COVID-19 和没有 COVID-19 的重症监护室患者念珠菌定植情况比较:土耳其首次前瞻性队列研究
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-08 DOI: 10.1093/mmy/myae035
Ilvana Çaklovica Küçükkaya, Günseli Orhun, Arif Atahan Çağatay, Sadık Kalaycı, Figen Esen, Fikrettin Şahin, Ali Ağaçfidan, Zayre Erturan
Candida species are the primary cause of fungal infections in intensive care units (ICUs). Despite the increasing prevalence of Candida-related infections, monitoring the progression of these infections from colonization in COVID-19 ICU patients lacks sufficient information. This study aims prospectively to compare 62 COVID-19 and 60 non-COVID-19 ICU patients from admission to discharge in terms of colonization development, rates, isolated Candida species, risk factors, and Candida infections during hospitalization. A total of 1464 samples collected at specific time intervals from various body sites [mouth, skin (axilla), rectal, and urine]. All samples were inoculated onto CHROMagar Candida and CHROMagar Candida Plus media, with isolates identified using MALDI-TOF MS. COVID-19 patients exhibited significantly higher colonization rates in oral, rectal, and urine samples compared to non-COVID-19 patients, (p<0.05). Among the Candida species, non-albicans Candida was more frequently detected in COVID-19 patients, particularly in oral (75.8%-25%; p<0.001) and rectal regions (74.19%-46.66%; p< 0.05). Colonization with mixed Candida species was also more prevalent in the oropharyngeal region (p<0.05). Mechanical ventilation and corticosteroid use emerged as elevated risk factors among COVID-19 patients (p<0.05). Despite the colonization prevalence, both COVID-19-positive and negative patients exhibited low incidences of Candida infections, with rates of 9.67% (n=6/62) and 6.67% (n=3/60), respectively. Consequently, although Candida colonization rates were higher in COVID-19 ICU patients, there was no significant difference in Candida infection development compared to the non-COVID-19 group. However, the elevated rate of non-albicans Candida isolates highlights potential future infections, particularly given their intrinsic resistance in prophylactic or empirical treatments if needed. Additionally, the high rate of mixed colonization emphasizes the importance of using chromogenic media for routine evaluation.
念珠菌是重症监护病房(ICU)真菌感染的主要原因。尽管念珠菌相关感染的发病率越来越高,但对 COVID-19 ICU 患者从定植开始的感染进展情况的监测却缺乏足够的信息。本研究旨在前瞻性地比较 62 名 COVID-19 和 60 名非 COVID-19 ICU 患者从入院到出院期间的定植发展、比率、分离念珠菌种类、风险因素和住院期间的念珠菌感染情况。在特定时间间隔内从不同身体部位(口腔、皮肤(腋窝)、直肠和尿液)共采集了 1464 份样本。所有样本均接种到 CHROMagar 念珠菌培养基和 CHROMagar Candida Plus 培养基上,并使用 MALDI-TOF MS 对分离菌株进行鉴定。与非 COVID-19 患者相比,COVID-19 患者在口腔、直肠和尿液样本中的定植率明显更高(p<0.05)。在念珠菌种类中,COVID-19 患者更常检测到非阿氏念珠菌,尤其是在口腔(75.8%-25%;p<0.001)和直肠区域(74.19%-46.66%;p<0.05)。混合念珠菌的定植在口咽部也更为普遍(p<0.05)。在 COVID-19 患者中,机械通气和皮质类固醇的使用成为高危因素(p<0.05)。尽管定植率很高,但 COVID-19 阳性和阴性患者的念珠菌感染发生率都很低,分别为 9.67%(n=6/62)和 6.67%(n=3/60)。因此,虽然 COVID-19 ICU 患者的念珠菌定植率较高,但与非 COVID-19 组相比,念珠菌感染的发生率并无显著差异。不过,非阿氏念珠菌分离率的升高凸显了未来可能发生的感染,特别是考虑到它们对预防性或经验性治疗(如需要)的内在抵抗力。此外,混合定植率较高也强调了使用显色培养基进行常规评估的重要性。
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引用次数: 0
Aflatoxin Profiles of Aspergillus flavus Isolates in Sudanese Fungal Rhinosinusitis 苏丹真菌性鼻炎中黄曲霉菌分离物的黄曲霉毒素图谱
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-04 DOI: 10.1093/mmy/myae034
Shaoqin Zhou, Mawahib A I Ismail, Vishukumar Aimanianda, G Sybren de Hoog, Yingqian Kang, Sarah A Ahmed
Aspergillus flavus is a commonly encountered pathogen responsible for fungal rhinosinusitis (FRS) in arid regions. The species is known to produce aflatoxins, posing a significant risk to human health. This study aimed to investigate the aflatoxin profiles of A. flavus isolates causing FRS in Sudan. A total of 93 clinical and 34 environmental A. flavus isolates were studied. Aflatoxin profiles were evaluated by phenotypic (thin-layer and high-performance chromatography) and genotypic methods at various temperatures and substrates. Gene expression of aflD and aflR was also analyzed. A total of 42/93 (45%) isolates were positive for aflatoxin B1 and AFB2 by HPLC. When incubation temperature changed from 28°C to 36°C, the number of positive isolates decreased to 41% (38/93). Genetic analysis revealed that 85% (79/93) of clinical isolates possessed all seven-aflatoxin biosynthesis-associated genes, while 27% (14/51) of non-producing isolates lacked specific genes (aflD / aflR / aflS). Mutations were observed in aflS and aflR genes across both aflatoxin-producers and non-producers. Gene expression of aflD and aflR showed the highest expression between the 4th and 6th days of incubation on Sabouraud medium and on the 9th day of incubation on RPMI medium. Aspergillus flavus clinical isolates demonstrated aflatoxigenic capabilities, influenced by incubation temperature and substrate. Dynamic aflD and aflR gene expression patterns over time enriched our understanding of aflatoxin production regulation. The overall findings underscored the health risks of Sudanese patients infected by this species, emphasizing the importance of monitoring aflatoxin exposure.
黄曲霉是干旱地区常见的真菌性鼻炎病原体。众所周知,黄曲霉菌会产生黄曲霉毒素,对人类健康构成重大威胁。本研究旨在调查苏丹引起鼻炎的黄曲霉菌分离物的黄曲霉毒素特征。共研究了 93 个临床黄曲霉分离株和 34 个环境黄曲霉分离株。在不同温度和底物条件下,通过表型(薄层色谱法和高效色谱法)和基因型方法对黄曲霉毒素谱进行了评估。此外,还分析了黄曲霉毒素的基因表达。通过高效液相色谱法,共有 42/93 株(45%)分离物对黄曲霉毒素 B1 和 AFB2 呈阳性。当培养温度从 28℃ 升至 36℃ 时,阳性分离物的数量下降到 41%(38/93)。基因分析表明,85%(79/93)的临床分离物具有所有七种黄曲霉毒素生物合成相关基因,而 27%(14/51)的非生产分离物缺乏特定基因(aflD / aflR / aflS)。在黄曲霉毒素生产者和非生产者中都观察到了 aflS 和 aflR 基因的突变。aflD和aflR的基因表达量在沙保鲁培养基上培养的第4-6天和RPMI培养基上培养的第9天最高。黄曲霉临床分离株具有黄曲霉致病能力,这受培养温度和底物的影响。随着时间的推移,aflD 和 aflR 基因的动态表达模式丰富了我们对黄曲霉毒素生产调控的认识。总体研究结果强调了苏丹患者感染黄曲霉毒素对健康造成的风险,并强调了监测黄曲霉毒素暴露的重要性。
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引用次数: 0
A guide to mycetisms: a toxicological and preventive overview. 霉菌指南:毒理学和预防概述。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-03 DOI: 10.1093/mmy/myae033
M. Benvenuti, M. Zotti, S. La Maestra
Fungi are often considered a delicacy and are primarily cultivated and harvested, although numerous species are responsible for intoxication due to toxin content. Foodborne diseases are a significant public health concern, causing approximately 420,000 deaths and 600 million morbidities yearly, of which mushroom poisoning is one of the leading causes. Epidemiological data on non-cultivated mushroom poisoning in individual countries are often unrepresentative, as intoxication rarely requires emergency intervention. On the other hand, the lack of specialist knowledge among medical personnel about the toxicological manifestations of mushroom consumption may result in ineffective therapeutic interventions. This work aims to provide an easy-to-consult and wide-ranging tool useful for better understanding the variability of mushroom intoxications, the associated symptoms, and the main treatments for the most severe cases, given the absence of a complete species mapping tool toxic. Moreover, we establish an effective collection network that describes the incidence of mushroom poisonings by reporting the species and associated toxicological manifestations for each case. In conclusion, we highlight the need to establish appropriate primary prevention interventions, such as training the affected population and increasing consultancy relationships between mycological experts and specialised healthcare personnel.
真菌通常被视为美味佳肴,主要用于栽培和收获,但许多种类的真菌因含有毒素而导致中毒。食源性疾病是一个重大的公共卫生问题,每年造成约 42 万人死亡,6 亿人发病,其中蘑菇中毒是主要原因之一。各个国家非栽培蘑菇中毒的流行病学数据往往不具代表性,因为中毒很少需要紧急干预。另一方面,医务人员对食用蘑菇的毒理学表现缺乏专业知识,可能导致治疗干预无效。由于缺乏完整的毒物物种图谱工具,这项工作旨在提供一个易于查询且范围广泛的工具,帮助人们更好地了解蘑菇中毒的变异性、相关症状以及最严重病例的主要治疗方法。此外,我们还建立了一个有效的收集网络,通过报告每个病例的物种和相关毒理学表现来描述蘑菇中毒的发生率。总之,我们强调有必要建立适当的初级预防干预措施,例如对受影响人群进行培训,增加真菌学专家和专业医护人员之间的咨询关系。
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引用次数: 0
Safety and pharmacokinetics of antifungal agent VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects: phase 1, first-in-Human, randomized, double-blind, placebo-controlled study of single-ascending oral doses of VT-1598. 抗真菌剂 VT-1598 及其主要代谢物 VT-11134 在健康成年受试者中的安全性和药代动力学:VT-1598 单剂量递增口服的第一阶段、人类首次、随机、双盲、安慰剂对照研究。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-04-03 DOI: 10.1093/mmy/myae032
Kenan Gu, Robert Spitz, Erin Hammett, Anna Jaunarajs, V. Ghazaryan, Edward P Garvey, T. Degenhardt
VT-1598 is a novel fungal CYP51 inhibitor and 1-tetrazole-based antifungal drug candidate with improved selectivity minimizing off-target binding to and inhibition of human CYP450 enzymes. Data are presented from this first clinical study in evaluation of the safety and pharmacokinetic (PK) of single ascending dose of 40, 80, 160, 320, and 640 mg VT-1598, comprising a 160 mg cohort in both fasting and fed states. Eight healthy adults per dose were randomized to receive either oral VT-1598 or placebo (3:1). Over the dose range, exposures were with relatively high variation. The maximum plasma concentrations (Cmax) for VT-1598 were 31.00 to 279.4 ng/mL and for its primary metabolite, VT-11134, were 27.80 to 108.8 ng/mL. Plasma area under the concentration-time curve to the last measurable concentration (AUC0-last) for VT-1598 were 116.1 to 4507 ng*h/mL, and for VT-11134 were 1140 to 7156 ng*h/mL. The dose proportionality was inconclusive based on the results of power model. The peak concentration time (Tmax) was 4 to 5 hr for VT-1598 and for VT-11134. Half-life was 103 to126 hr for VT-11134. After food intake, Cmax of VT-1598 increased by 44% (geometric mean ratio (GMR), 1.44; 90%CI [0.691, 2.19]) and AUC0-last by 126% (GMR, 2.26; 90%CI [1.09, 3.44]), while exposure of VT-11134 was decreased 23% for Cmax (GMR, 0.77; 90%CI [0.239, 1.31]) and unchanged for AUC0-last (GMR, 1.02; 90%CI [0.701, 1.33]). Neither VT-1598 nor VT-11134 were detected in urine. No serious adverse events (AEs) or AEs leading to early termination were observed. The safety and PK profiles of VT-1598 support its further clinical development.
VT-1598 是一种新型真菌 CYP51 抑制剂和 1-四氮唑类抗真菌候选药物,具有更好的选择性,能最大限度地减少与人类 CYP450 酶的脱靶结合和抑制作用。这项首次临床研究评估了单次递增剂量为 40、80、160、320 和 640 毫克 VT-1598(包括空腹和进食状态下的 160 毫克组群)的安全性和药代动力学(PK)。每个剂量有 8 名健康成人随机接受口服 VT-1598 或安慰剂(3:1)。在剂量范围内,暴露量的变化相对较大。VT-1598 的最大血浆浓度(Cmax)为 31.00 至 279.4 纳克/毫升,其主要代谢物 VT-11134 的最大血浆浓度(Cmax)为 27.80 至 108.8 纳克/毫升。VT-1598 至最后可测量浓度的血浆浓度时间曲线下面积(AUC0-last)为 116.1 至 4507 纳克*小时/毫升,VT-11134 为 1140 至 7156 纳克*小时/毫升。根据幂模型的结果,剂量比例关系尚无定论。VT-1598 和 VT-11134 的峰值浓度时间(Tmax)为 4 至 5 小时。VT-11134 的半衰期为 103 至 126 小时。摄入食物后,VT-1598 的 Cmax 增加了 44%(几何平均比 (GMR),1.44;90%CI [0.691,2.19]),AUC0-last 增加了 126%(GMR,2.26;90%CI [1.09,3.44]),而 VT-11134 的 Cmax 暴露降低了 23%(GMR,0.77;90%CI [0.239,1.31]),AUC0-last 暴露不变(GMR,1.02;90%CI [0.701,1.33])。尿液中未检测到 VT-1598 或 VT-11134。未发现严重不良事件或导致提前终止的不良事件。VT-1598的安全性和PK特征支持其进一步的临床开发。
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引用次数: 0
Isolation of azole-resistant Aspergillus spp. from food products. 从食品中分离抗唑曲霉菌属。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-03-28 DOI: 10.1093/mmy/myae026
Satomi Uehara, Yumi Takahashi, Keiko Iwakoshi, Yukari Nishino, Kotono Wada, Asuka Ono, Daisuke Hagiwara, Takashi Chiba, Keiko Yokoyama, Kenji Sadamasu

The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.

耐唑类曲霉菌在全球范围内的流行率正在上升,据推测这与使用唑类杀虫剂有关。曲霉菌病的致病菌曲霉菌属可能通过食物带入住宅。然而,有关食品中抗唑曲霉菌属的研究十分有限。因此,我们从加工食品和商业农产品中分离出曲霉菌属,并进行了唑类药物药敏试验。在 692 个食物样本中,我们从 50 个食物样本分离出 99 株曲霉菌属,包括蔬菜(22.9%)、柑橘类水果(26.3%)、谷类(25.5%)和加工食品(1.8%)。分离出的菌株分属 8 个部分的 18 个菌种:曲霉属、念珠菌属、克拉瓦蒂属、黄曲霉属、烟曲霉属、尼杜兰菌属、尼格里菌属和特雷菌属。分离最多的是 Fumigati,有 39 株,其次是 Nigri,有 28 株。主要菌种为烟曲霉和韦氏烟曲霉。有 10 个烟曲霉菌株和 4 个隐性菌株、4 个黑曲霉隐性菌株、2 个黄曲霉菌株和 4 个赤霉菌株超过了唑类的流行病学临界值。管胞酵母菌(A. tubingensis)、假病毒酵母菌(A. pseudoviridinutans)、褐酵母菌(A. lentulus)、赤酵母菌(A. terreus)和平酵母菌(N. hiratsukae)对多种唑类药物的敏感性较低。发现含有农产品的食品受到曲霉菌属的污染,65.3%的分离物的最小抑菌浓度低于流行病学临界值。我们的研究为阐明食物、环境和临床上重要的曲霉菌属之间的关系奠定了基础。
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引用次数: 0
Use of the Mucorales qPCR on blood to screen high-risk hematology patients is associated with better survival. 使用血液中的粘菌 qPCR 来筛查高风险血液病患者,可提高患者的存活率。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-03-28 DOI: 10.1093/mmy/myae030
Anne-Pauline Bellanger, Houssein Gbaguidi-Haore, Ana Berceanu, Laura Gouzien, Chaima El Machhour, Damien Bichard, Fanny Lanternier, Emeline Scherer, Laurence Millon

Our objective was to determine whether the twice-weekly screening of high-risk hematology patients by Mucorales qPCR on serum affects the prognosis of mucormycosis. Results from all serum Mucorales qPCR tests performed on patients from the hematology unit from January 2017 to December 2022 were analyzed. Patients with positive results were classified as having proven, probable or 'PCR-only' mucormycosis. One-month mortality for the local cohort was compared with that of a national cohort of cases of mucormycosis collected by the French surveillance network for invasive fungal disease ('Réseau de surveillances des infections fongiques invasives en France' (RESSIF)) from 2012 to 2018. From 2017 to 2022, 7825 serum Mucorales qPCR tests were performed for patients from the hematology unit; 107 patients with at least one positive Mucorales qPCR (164 positive samples) were identified. Sixty patients (70 positive samples, median Cq = 40) had no radiological criteria for mucormycosis and were considered not to have invasive fungal disease (70/7825, 0.9% false positives). It was not possible to classify disease status for six patients (12 positive samples, median Cq = 38). Forty-one patients (82 positive samples, median Cq = 35) had a final diagnosis of mucormycosis. In comparison with the RESSIF cohort, the local cohort was independently associated with a 48% lower one-month all-cause mortality rate (age-, sex-, and primary disease-adjusted hazard ratio = 0.52; 95% confidence interval: 0.29-0.94; P 0.03). Proactive screening for invasive mold diseases in high-risk hematology patients, including twice-weekly Mucorales qPCR on serum, was associated with mucormycosis higher survival.

我们的目的是确定每周两次通过血清粘孢子菌 qPCR 对高危血液科患者进行筛查是否会影响粘孢子菌病的预后。我们分析了 2017 年 1 月至 2022 年 12 月期间对血液科患者进行的所有血清粘孢子qPCR检测结果。结果呈阳性的患者被分为已证实、可能或 "仅 PCR "粘孢子菌病。当地队列的一个月死亡率与法国侵袭性真菌疾病监测网络("Réseau de surveillances des infections fongiques invasives en France",RESSIF)从2012年至2018年收集的全国队列粘孢子菌病病例死亡率进行了比较。从 2017 年到 2022 年,血液科对 7825 名患者进行了血清粘孢子菌 qPCR 检测;发现 107 名患者至少有一次粘孢子菌 qPCR 检测呈阳性(164 份阳性样本)。有 60 名患者(70 份阳性样本,中位 Cq = 40)未达到粘孢子菌病的放射学标准,被认为未患侵袭性真菌病(70/7825,假阳性率为 0.9%)。有 6 名患者(12 份阳性样本,中位 Cq = 38)无法进行疾病状态分类。41 名患者(82 份阳性样本,中位 Cq = 35)最终确诊为粘孢子菌病。与 RESSIF 队列相比,当地队列的一个月全因死亡率降低了 48%(年龄、性别和原发病调整后危险比 = 0.52;95% 置信区间:0.29-0.94;P 0.03)。对高风险血液病患者进行侵入性霉菌疾病的积极筛查,包括每周两次对血清进行粘孢子菌 qPCR 检测,与粘孢子菌病的较高存活率有关。
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引用次数: 0
Histoplasma antigens as novel players for the development of new enzyme immunoassays for the serodiagnosis of histoplasmosis: A comparative study of their analytical performance. 将组织胞浆菌抗原作为开发用于组织胞浆菌病血清诊断的新型酶免疫测定的新型参与者:对其分析性能的比较研究。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-03-28 DOI: 10.1093/mmy/myae023
Carolina Rodríguez Laboccetta, Víctor J Briceño Fernández, Agustín Videla Garrido, Gladys B Posse, María L Cuestas, Alejandro D Nusblat

Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.

组织胞浆菌病的明确诊断依赖于培养和/或细胞学/组织病理学;然而,这些程序的灵敏度有限,而且培养耗时。免疫扩散法检测抗体对免疫力低下的人来说灵敏度较低,而且使用的试剂是组织胞浆素(HMN),一种粗抗原提取物。最近,人们发现了新的候选蛋白抗原,并通过 DNA 重组技术生产出了用于诊断组织胞浆菌病的标准化特异性试剂。以不同的荚膜组织胞浆菌抗原为试剂,比较用于诊断组织胞浆菌病抗体检测的新型 ELISAs 的分析性能。通过 DNA 重组技术制备了荚膜组织胞浆菌 100kDa 蛋白(Hcp100)、M 抗原及其免疫反应片段 F1。半乳甘露聚糖是从酵母细胞壁和菌丝细胞壁(分别为 yGM 和 mGM)中纯化出来的。我们评估了 ELISA 试验在血清学检测这些抗原抗体方面的分析性能,并将其与使用 HMN 作为试剂获得的结果进行了比较。Hcp100 ELISA检测抗体的灵敏度为90.0%,特异度为92.0%;而M ELISA的灵敏度为43.3%,特异度为95.0%;F1 ELISA的灵敏度为33.3%,特异度为84.0%;yGM ELISA的灵敏度为96.7%,特异度为94.0%;mGM ELISA的灵敏度为83.3%,特异度为88.0%;HMN ELISA的灵敏度为70.0%,特异度为86.0%。总之,Hcp100 被认为是最有希望用于组织胞浆菌病血清诊断的候选物质。事实证明,HMN 的主要免疫反应元素是 GM 而非 M 抗原。不过,与 M 抗原相比,GM 抗原的交叉反应发生率更高。
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引用次数: 0
COVID-19 associated candidemia: From a shift in fungal epidemiology to a rise in azole drug resistance. 与 COVID -19 相关的念珠菌血症:从真菌流行病学的转变到唑类药物耐药性的上升。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-03-28 DOI: 10.1093/mmy/myae031
Mohammad Javad Najafzadeh, Tahmineh Shaban, Hossein Zarrinfar, Alireza Sedaghat, Neginsadat Hosseinikargar, Fariba Berenji, Mahsa Jalali, Michaela Lackner, Jasper Elvin James, Macit Ilkit, Cornelia Lass-Flörl

Our understanding of fungal epidemiology and the burden of antifungal drug resistance in COVID-19-associated candidemia (CAC) patients is limited. Therefore, we conducted a retrospective multicenter study in Iran to explore clinical and microbiological profiles of CAC patients. Yeast isolated from blood, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method M27-A3 protocol. A total of 0.6% of the COVID-19 patients acquired CAC (43/6174). Fluconazole was the most widely used antifungal, and 37% of patients were not treated. Contrary to historic candidemia patients, Candida albicans and C. tropicalis were the most common species. In vitro resistance was high and only noted for azoles; 50%, 20%, and 13.6% of patients were infected with azole-non-susceptible (ANS) C. tropicalis, C. parapsilosis, and C. albicans isolates, respectively. ERG11 mutations conferring azole resistance were detected for C. parapsilosis isolates (Y132F), recovered from an azole-naïve patient. Our study revealed an unprecedented rise in ANS Candida isolates, including the first C. parapsilosis isolate carrying Y132F, among CAC patients in Iran, which potentially threatens the efficacy of fluconazole, the most widely used drug in our centers. Considering the high mortality rate and 37% of untreated CAC cases, our study underscores the importance of infection control strategies and antifungal stewardship to minimize the emergence of ANS Candida isolates during COVID-19.

我们对 COVID-19 相关念珠菌血症(CAC)患者的真菌流行病学和抗真菌药物耐药性负担了解有限。因此,我们在伊朗开展了一项回顾性多中心研究,以了解 CAC 患者的临床和微生物学特征。从血液中分离出的酵母菌通过基质辅助激光解吸/电离飞行时间质谱法进行鉴定,并使用肉汤微稀释法 M27-A3 方案进行抗真菌药敏试验 (AFST)。COVID-19患者中共有0.6%感染了CAC(43/6174)。氟康唑是使用最广泛的抗真菌药物,37%的患者未接受治疗。与历史上的念珠菌血症患者相反,白念珠菌和热带念珠菌是最常见的菌种。体外耐药性很高,而且只对唑类产生耐药性;分别有50%、20%和13.6%的患者感染了对唑类不敏感(ANS)的热带念珠菌、副丝状念珠菌和白念珠菌分离株。从一名对唑不敏感的患者身上分离出的副丝虫(Y132F)检出了ERG11突变,从而产生了对唑的耐药性。我们的研究表明,在伊朗的 CAC 患者中,ANS 念珠菌分离株的数量出现了前所未有的增长,其中包括首个携带 Y132F 的副丝状念珠菌分离株,这可能会威胁到氟康唑的疗效,而氟康唑是我们中心最广泛使用的药物。考虑到高死亡率和 37% 的 CAC 病例未经治疗,我们的研究强调了感染控制策略和抗真菌管理的重要性,以尽量减少 COVID-19 期间 ANS 念珠菌分离株的出现。
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Medical mycology
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