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High diversity of yeast species and strains responsible for vulvovaginal candidiasis in South-East Gabon 加蓬东南部引起外阴阴道念珠菌病的酵母菌种类和菌株的高度多样性
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2022.101354
M. Bignoumba , R. Onanga , B.S. Kumulungui , R.F. Kassa Kassa , Y. Mouanga Ndzime , K. Mbombe Moghoa , D. Stubbe , P. Becker

Objectives

Candida albicans generally remains the principal pathogenic yeast responsible for vulvovaginal candidiasis (VVC), although with variable prevalence. In this study, we evaluated the evolution of the prevalence of the non-Candida albicans Candida (NCAC) species and investigated the genotypic diversity and the population genetic structure of the circulating C. albicans strains associated with VVC in the vicinity of Franceville (Gabon).

Methods

A total of 110 independent isolates were identified using both MALDI-TOF MS and conventional techniques. The population genetic structure of the C. albicans strains was determined by multiple locus variable-number tandem repeat analysis using 4 microsatellite markers.

Results

The mean and median age of the patients was 31 years. Seven patients had a mixed infection. C. albicans accounted for 62 % (n=68) of the total isolates. NCAC were dominated by C. glabrata, followed by P. kudriavzevii, C. parapsilosis, C. tropicalis, M. guilliermondii, and C. nivariensis. The cluster analysis revealed a high diversity, with a total of 50 different genotypes. The most represented genotype was shared by only four strains, while the vast majority (39 strains) had a unique MLVA pattern. Geographic clusters were not detected.

Conclusion

The study provides information on species distribution and possible changing epidemiology while reporting for the first time C. nivariensis in VVC in Africa. This study is also the first to investigate the genotypic diversity of the circulating C. albicans strains associated with VVC in Central Africa. Such analyses would help understand the molecular epidemiology of C. albicans.

目的白色念珠菌通常仍然是导致外阴阴道念珠菌病(VVC)的主要致病酵母,尽管其患病率各不相同。在本研究中,我们评估了非白色念珠菌Candida(NCAC)物种的流行演变,并调查了在加蓬Franceville附近与VVC相关的循环白色念珠菌菌株的基因型多样性和群体遗传结构。利用4个微卫星标记,通过多基因座可变数串联重复分析确定了白色念珠菌菌株的群体遗传结构。结果患者的平均和中位年龄为31岁。7名患者有混合感染。白色念珠菌占分离株总数的62%(n=68)。NCAC主要由光滑乳杆菌(C.glabrata)为主,其次是库氏乳杆菌(P.kudriavzevii)、副psilosis乳杆菌、热带乳杆菌(C.tropicalis)、吉列蒙迪乳杆菌(M.guilliermondii)和尼瓦里乳杆菌(C.nivariensis)。聚类分析显示出高度多样性,共有50种不同的基因型。最具代表性的基因型仅由四个菌株共享,而绝大多数(39个菌株)具有独特的MLVA模式。未检测到地理群集。结论该研究首次报道了非洲VVC中的雪腐镰刀菌的物种分布和可能的流行病学变化。这项研究也是首次调查中非与VVC相关的循环白色念珠菌菌株的基因型多样性。这样的分析将有助于了解白色念珠菌的分子流行病学。
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引用次数: 0
Detection of Pneumocystis jirovecii by PCR in patients with lung cancer: A preliminary study PCR检测肺癌患者肺孢子虫的初步研究
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101365
Ozlem Ulusan Bagci , Filiz Guldaval , Can Muftuoglu , Ufuk Mert , Seray Toz , Damla Serce Unat , Omer Selim Unat , Gulru Polat , Ayse Caner

Introduction

Infection complications in lung cancer (LC), one of the most common cancers in the world, are still among the most important causes of death. Of them, P. jirovecii, which is as an opportunistic infection, causes a life-threatening type of pneumonia in cancer patients. This preliminary study aimed to determine the incidence and clinical status of P. jirovecii by PCR in lung cancer patients compared to the conventional method.

Material and methods

Sixty-nine lung cancer patients and fSorty healthy individuals were included in the study. After sociodemographical and clinical features were recorded, sputum samples were collected from attenders. Firstly, microscopic examination was made with Gomori's methenamine silver stain and then PCR was performed.

Results

P. jirovecii was detected in three of 69 lung cancer patients by PCR (4.3%), but not by microscopy. However, healthy individuals were negative for P. jirovecii by both methods. Based on clinical and radiological findings, P. jirovecii was evaluated as probable infection in one patient and colonization in the other two patients. Although PCR is more sensitive than conventional staining methods, it cannot distinguish probable and proven infections from pulmonary colonization.

Discussion

It is important to evaluate the decision of infection together with laboratory, clinical and radiological findings. Moreover, PCR may enable to know the colonization and to take precautions such as prophylaxis, due to the risk of colonization turning into an infection in immunocompromised patient groups. Further studies involving larger populations and evaluating the colonization-infection relationship in patients with solid tumors are needed.

癌症是世界上最常见的癌症之一,其感染并发症仍然是最重要的死亡原因之一。其中,P.jirovecii是一种机会性感染,会导致癌症患者患上危及生命的肺炎。本初步研究旨在与传统方法相比,通过PCR测定癌症患者中吉罗韦氏疟原虫的发病率和临床状况。材料和方法研究纳入了癌症的16例患者和16例健康人。在记录了社会人口学和临床特征后,从就诊者身上采集痰液样本。首先用Gomori’s methenamine银染进行显微镜检查,然后进行PCR。结果P。69例癌症患者中有3例(4.3%)经PCR检测到jirovecii,但显微镜下未检测到。然而,健康个体在两种方法中均对吉若韦奇P.jirovecii呈阴性。根据临床和放射学检查结果,对一名患者的吉若韦奇P.jirovecii可能感染和另外两名患者的定植进行了评估。尽管PCR比传统染色方法更敏感,但它无法区分可能的和已证实的感染与肺部定植。讨论结合实验室、临床和放射学检查结果来评估感染的决定是很重要的。此外,由于免疫功能受损患者群体的定植转化为感染的风险,PCR可以了解定植并采取预防措施,如预防。需要进一步的研究涉及更大的人群,并评估实体瘤患者的定植-感染关系。
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引用次数: 0
Disseminated Medicopsis romeroi infection in a kidney transplant recipient: A case report 肾移植受者播散性苦参感染1例报告
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2022.101355
Bhavana Ganduri, R. Sujith, Praveen Tirlangi, Ravikiran Nalla, Sadhana Y. Veturi, Gagandeep Singh, Immaculata Xess, S R Keithi-Reddy

Medicopsis romeroi is a rare, dematiaceous fungus that is difficult to identify using conventional fungal tests. Although uncommon, immunocompromised patients are particularly susceptible to this opportunistic fungus. Here, we report the case of a renal transplant recipient who presented with painful disseminated subcutaneous and soft tissue lesions. Sequencing of the Internal transcribed spacer (ITS) region of the ribosomal DNA identified the fungus as Medicopsis romeroi. Additionally, tissue samples from a non-healing wound on the left forearm grew Rhizopus spp. on Sabouraud dextrose agar, indicating a Mucormycosis superinfection. The patient's condition improved with surgical intervention and antifungal therapy with Posaconazole and Terbinafine. This case demonstrates the need for a high index of suspicion in order to facilitate early diagnosis and treatment and thus reduce the risk of dissemination.

梅德罗Medicopsis romeroi是一种罕见的暗色真菌,很难通过传统的真菌测试进行鉴定。尽管不常见,但免疫功能低下的患者特别容易感染这种机会真菌。在此,我们报告了一例肾移植受者,其表现为疼痛的皮下和软组织播散性病变。对核糖体DNA的内部转录间隔区(ITS)进行测序,确定该真菌为梅德罗Medicopsis romeroi。此外,左前臂未愈合伤口的组织样本在沙氏葡萄糖琼脂上生长出根霉属,表明存在毛霉菌病重叠感染。通过手术干预和泊沙康唑和特比萘芬的抗真菌治疗,患者的病情有所改善。该病例表明,需要高怀疑指数,以便于早期诊断和治疗,从而降低传播风险。
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引用次数: 0
Fungal keratitis caused by Coniochaeta mutabilis—A case report 变异Coniochaeta引起真菌性角膜炎1例
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101384
Jadesola Oremosu , Lawson Ung , James Chodosh , Connie Cañete-Gibas , Nathan P. Wiederhold , Emma C. Davies , Paulo J.M. Bispo

We present a rare case of recalcitrant fungal keratitis caused by Coniochaeta mutabilis, successfully managed with a course of oral, topical, intrastromal, and intracameral antifungals. A 57-year-old male on their fourth week of treatment for presumed left herpes simplex keratitis presented to clinic with severe left-sided foreign body sensation after gardening in his yard. On examination, a white corneal plaque was observed at 8 o'clock, shown to be a dense collection of fungal hyphae on confocal microscopy. Corneal cultures revealed yeast-like cells, initially identified as Kabatiella zeae by matching 100% identity with K. zeae strains CBS 767.71 and CBS 265.32 in BLASTn search using the internal transcribed spacer (ITS) sequence. Treated for over four months with topical amphotericin B and oral voriconazole without improvement, recourse to intrastromal and intracameral amphotericin B injections, coupled with the application of cyanoacrylate glue to the lesion and a bandage contact lens, led to eventual resolution. The patient subsequently underwent cataract surgery, achieving a BCVA of 20/20 in the eye. Surprisingly, upon further sequence analyses of combined ITS and large subunit ribosomal ribonucleic acid (LSU) and investigation of the K. zeae German strain CBS 767.71, the organism was revealed to be Coniochaeta mutabilis (formerly Lecythospora mutabilis). This means that the correct name for CBS 767.71 and CBS 265.32 is C. mutabilis and should be corrected in the GenBank record to avoid misleading identification in the future. This case also underscores the urgent unmet need for improved molecular diagnostic modalities in the care of corneal infections

我们报告了一例罕见的顽固性真菌性角膜炎,由变异Coniochaeta引起,成功地通过口服,局部,眼内和眼内的抗真菌药物治疗。一名57岁男性,因疑似左侧单纯疱疹角膜炎治疗第四周,在庭院园艺后出现严重的左侧异物感。检查时,8点钟方向可见白色角膜斑块,共聚焦显微镜下可见真菌菌丝密集聚集。角膜培养发现酵母样细胞,利用内部转录间隔序列(ITS)在BLASTn搜索中与玉米卡氏菌CBS 767.71和CBS 265.32的一致性达到100%,初步鉴定为玉米卡氏菌(Kabatiella zeae)。外用两性霉素B和口服伏立康唑治疗了4个多月,没有改善,求助于粘膜内和肠腔内注射两性霉素B,加上在病变处应用氰基丙烯酸酯胶和绷带接触镜,最终得到了解决。患者随后接受了白内障手术,眼部BCVA达到20/20。令人惊讶的是,通过ITS和大亚基核糖体核糖核酸(LSU)的进一步序列分析和对玉米科德国菌株CBS 767.71的调查,该生物被发现是Coniochaeta mutabilis(原Lecythospora mutabilis)。这意味着CBS 767.71和CBS 265.32的正确名称是C. mutabilis,应该在GenBank记录中进行更正,以避免将来的误导性识别。这个病例也强调了迫切需要改善分子诊断模式在角膜感染的护理
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引用次数: 1
Trends of CNS Cryptococcosis during Pre- and Post-HIV era: A 38 years’ retrospective cohort analysis from south India 艾滋病毒前和后时期中枢神经系统隐球菌病的趋势:来自印度南部的38年回顾性队列分析
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101358
Shayanki Lahiri , Sayani Maji , Netravathi Manjunath , Veenakumari H Bahubali , Nagarathna Chandrashekar

Objective

Central nervous system cryptococcosis (CNSc) is an AIDS defining opportunistic infection. This retrospective study aimed to analyze the changing epidemiology of CNSc cases from the period of pre- to post-emergence of HIV epidemic in south India.

Methods

Confirmed cases of CNSc from 1978 to 2015 were analyzed for demographic and clinical details with special reference to the cases diagnosed in south India during the period 1952–1977. Geographical distribution, affected age groups, clinical aspects, and comorbidities in relation to immune status were analysed

Results

The highest number of CNSc cases (n = 125) were recorded in 2006, with 89.6% HIV positivity. The highest HIV-positivity (93.6%) was documented in the years 2002 and 2009. CNSc cases have majorly changed after the introduction and spread of HIV in terms of predisposing factors, comorbidities, severity, affected age groups and treatment. Notably, an overall rise was observed in non-HIV associated CNSc cases from 1997 (8.1%) to 2015 (16.9%).

Conclusion

The peak of CNSc had already reached in south India during 2005–2006. However, the number of new infections has slowly decreased in last ten years. Progressive awareness and, early diagnosis of HIV and cryptococcosis, adequate availability of HAART and potential antifungal therapy has played crucial roles in changing epidemiology of the CNSc and its associated mortality.

目的中枢神经系统隐球菌病(CNSc)是一种艾滋病定义的机会性感染。本回顾性研究旨在分析印度南部HIV流行前后CNSc病例流行病学的变化。方法分析1978年至2015年确诊的CNSc病例的人口统计学和临床细节,特别是1952年至1977年在印度南部诊断的病例。分析了地理分布、受影响的年龄组、临床方面以及与免疫状态相关的合并症。结果2006年记录的CNSc病例数最高(n=125),HIV阳性率为89.6%。2002年和2009年记录的艾滋病毒阳性率最高(93.6%)。在HIV引入和传播后,CNSc病例在易感因素、合并症、严重程度、受影响的年龄组和治疗方面发生了重大变化。值得注意的是,从1997年(8.1%)到2015年(16.9%),非HIV相关的CNSc病例总体上升。结论2005-2006年,印度南部的CNSc已经达到峰值。然而,在过去的十年里,新感染的人数已经慢慢减少。对HIV和隐球菌病的逐渐认识和早期诊断、HAART的充分可用性和潜在的抗真菌治疗在改变CNSc的流行病学及其相关死亡率方面发挥了至关重要的作用。
{"title":"Trends of CNS Cryptococcosis during Pre- and Post-HIV era: A 38 years’ retrospective cohort analysis from south India","authors":"Shayanki Lahiri ,&nbsp;Sayani Maji ,&nbsp;Netravathi Manjunath ,&nbsp;Veenakumari H Bahubali ,&nbsp;Nagarathna Chandrashekar","doi":"10.1016/j.mycmed.2023.101358","DOIUrl":"10.1016/j.mycmed.2023.101358","url":null,"abstract":"<div><h3>Objective</h3><p><span>Central nervous system </span>cryptococcosis<span> (CNSc) is an AIDS defining opportunistic infection<span>. This retrospective study aimed to analyze the changing epidemiology of CNSc cases from the period of pre- to post-emergence of HIV epidemic in south India.</span></span></p></div><div><h3>Methods</h3><p>Confirmed cases of CNSc from 1978 to 2015 were analyzed for demographic and clinical details with special reference to the cases diagnosed in south India during the period 1952–1977. Geographical distribution, affected age groups, clinical aspects, and comorbidities in relation to immune status were analysed</p></div><div><h3>Results</h3><p>The highest number of CNSc cases (<em>n</em><span> = 125) were recorded in 2006, with 89.6% HIV positivity. The highest HIV-positivity (93.6%) was documented in the years 2002 and 2009. CNSc cases have majorly changed after the introduction and spread of HIV in terms of predisposing factors, comorbidities, severity, affected age groups and treatment. Notably, an overall rise was observed in non-HIV associated CNSc cases from 1997 (8.1%) to 2015 (16.9%).</span></p></div><div><h3>Conclusion</h3><p><span>The peak of CNSc had already reached in south India during 2005–2006. However, the number of new infections has slowly decreased in last ten years. Progressive awareness and, early diagnosis of HIV and cryptococcosis, adequate availability of HAART and potential </span>antifungal therapy has played crucial roles in changing epidemiology of the CNSc and its associated mortality.</p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9510299","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: 1
Reversible deafness and blindness in Cryptococcus gattii meningitis with a ventriculoperitoneal shunt: A case report and literature review 加蒂隐球菌脑膜炎合并脑室-腹膜分流的可逆性耳聋和失明:1例报告并文献复习
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101357
Anni Wang , Jia Liu , Junyu Liu , Lu Yang , Shiqi Yao , Bang-e Qin , Zhihui Su , Xiaofeng Xu , Han Xia , Ying Jiang , Fuhua Peng

Cryptococcus gattii (C. gattii) has been considered a leading cause of meningitis in immunocompetent hosts in tropical and subtropical regions. Visual loss is common but hearing impairment is relatively infrequent in C. gattii meningitis. Notably, there have been limited studies on the etiology, and especially therapy of auditory and ocular complications associated with C. gattii meningitis. Here we report a case of reversible deafness and blindness treated with a ventriculoperitoneal shunt (VPS) surgery in C. gattii meningitis. This case indicated that elevated intracranial pressure (ICP) may play a role in the concurrent hearing and vision impairments associated with C. gattii meningitis and the early VPS surgery after the initiation of the antifungal therapy may effectively improve both hearing and vision in this condition.

gattii隐球菌(C.gattii)被认为是热带和亚热带地区免疫活性宿主脑膜炎的主要原因。视觉丧失是常见的,但听力损伤相对罕见的C.gattii脑膜炎。值得注意的是,对病因的研究有限,尤其是对与先天性脑膜炎相关的听觉和眼部并发症的治疗。本文报告一例经脑室-腹腔分流术(VPS)治疗先天性脑膜炎的可逆性耳聋和失明病例。该病例表明,颅内压升高(ICP)可能在加蒂氏菌脑膜炎并发的听力和视力损伤中发挥作用,在开始抗真菌治疗后进行早期VPS手术可以有效改善这种情况下的听力和视觉。
{"title":"Reversible deafness and blindness in Cryptococcus gattii meningitis with a ventriculoperitoneal shunt: A case report and literature review","authors":"Anni Wang ,&nbsp;Jia Liu ,&nbsp;Junyu Liu ,&nbsp;Lu Yang ,&nbsp;Shiqi Yao ,&nbsp;Bang-e Qin ,&nbsp;Zhihui Su ,&nbsp;Xiaofeng Xu ,&nbsp;Han Xia ,&nbsp;Ying Jiang ,&nbsp;Fuhua Peng","doi":"10.1016/j.mycmed.2023.101357","DOIUrl":"10.1016/j.mycmed.2023.101357","url":null,"abstract":"<div><p><span><em>Cryptococcus gattii</em></span> (<em>C. gattii</em><span>) has been considered a leading cause of meningitis in immunocompetent hosts in tropical and subtropical regions. Visual loss is common but hearing impairment is relatively infrequent in </span><em>C. gattii</em> meningitis. Notably, there have been limited studies on the etiology, and especially therapy of auditory and ocular complications associated with <em>C. gattii</em><span><span> meningitis. Here we report a case of reversible deafness and blindness treated with a </span>ventriculoperitoneal shunt (VPS) surgery in </span><em>C. gattii</em><span> meningitis. This case indicated that elevated intracranial pressure (ICP) may play a role in the concurrent hearing and vision impairments associated with </span><em>C. gattii</em><span> meningitis and the early VPS surgery after the initiation of the antifungal therapy may effectively improve both hearing and vision in this condition.</span></p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455444","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
Review: The application of corticosteroids in cryptococcal meningitis 综述:皮质类固醇在隐球菌性脑膜炎中的应用
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101364
Junyu Liu , Jia Liu , Lu Yang, Xiaofeng Xu, Qin Bang-e, Ying Jiang, Fuhua Peng

Cryptococcal meningitis (CM) is a serious disease with high morbidity and mortality. Although the patients who received corticosteroids were at high risk of having CM, corticosteroids also have been used as an adjunct to antifungal drugs for treating people with CM in some situations (such as immune reconstitution inflammatory syndrome, cerebral cyptococcoma, et al.). Here, we summarize the current knowledge on the application of the corticosteroids in CM, aiming to help clinicians to reasonably use corticosteroids in patients with CM.

隐球菌性脑膜炎(CM)是一种发病率和死亡率较高的严重疾病。尽管接受皮质类固醇治疗的患者患有CM的风险很高,但皮质类固醇也被用作抗真菌药物的辅助药物,用于治疗某些情况下的CM患者(如免疫重建炎症综合征、脑cytococoma等)。在这里,我们总结了皮质类固醇在CM中应用的最新知识,旨在帮助临床医生在CM患者中合理使用皮质类固醇。
{"title":"Review: The application of corticosteroids in cryptococcal meningitis","authors":"Junyu Liu ,&nbsp;Jia Liu ,&nbsp;Lu Yang,&nbsp;Xiaofeng Xu,&nbsp;Qin Bang-e,&nbsp;Ying Jiang,&nbsp;Fuhua Peng","doi":"10.1016/j.mycmed.2023.101364","DOIUrl":"10.1016/j.mycmed.2023.101364","url":null,"abstract":"<div><p><span><span>Cryptococcal meningitis (CM) is a serious disease with high morbidity and mortality. Although the patients who received corticosteroids were at high risk of having CM, corticosteroids also have been used as an adjunct to </span>antifungal drugs for treating people with CM in some situations (such as </span>immune reconstitution inflammatory syndrome<span>, cerebral cyptococcoma, et al.). Here, we summarize the current knowledge on the application of the corticosteroids in CM, aiming to help clinicians to reasonably use corticosteroids in patients with CM.</span></p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455980","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
In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus 金糠蛋白对耐伊曲康唑烟曲霉的体外抑菌及抗菌活性研究
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101381
Peiying Chen , Jing Yang , Yuanling Jin , Chujie Lu , Zhenzhen Feng , Fei Gao , Yuan Chen , Fuling Wang , Zhuo Shang , Wei Lin

Background

Infections caused by azole-resistant Aspergillus are a rising public health threat with high mortality rates, high treatment costs and limited available antifungals, indicating an urgent need for new antifungals or strategies. Our aim was to investigate antifungal and antibiofilm activities of auranofin, an FDA-approved anti-antirheumatic drug.

Methods

Fungal susceptibility testing for auranofin was carried out by the broth-based microdilution methods. Cell viability treated by auranofin was tested by resazurin dye testing. The synergistic effect of auranofin and antifungal drugs was evaluated using checkboard assay. The inhibitory of biofilms were measured by crystal violet staining. Gene expression level analysis and enzyme activity was investigated with qRT-PCR analysis and DTNB assay. The key amino acid residues in the binding of auranofin with A. fumigatus thioredoxin reductase (AfTrxR) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays.

Results

Auranofin has fungicidal activity and in vitro antifungal spectrum including Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Aspergillus niger, even itraconazole (ITC)-resistant A. fumigatus. Additionally, it has antibiofilm activities against ITC-resistant A. fumigatus by reducing the expression level of SomA and MedA. Moreover, we discovered a synergistic effect of auranofin and ITC or amphotericin B against ITC-resistant A. fumigatus. Auranofin downregulated the gene transcription of AfTrxR, and strongly inhibited the enzyme activity of AfTrxR through interacting with residues C145 and C148.

Conclusions

Auranofin has fungicidal and antibiofilm activities in Aspergillus spp. and is also a potentiator of ITC or amphotericin B in vitro.

背景抗唑曲霉菌引起的感染是一种日益严重的公共卫生威胁,死亡率高,治疗成本高,可用的抗真菌药物有限,这表明迫切需要新的抗真菌药或策略。我们的目的是研究金诺芬的抗真菌和抗生物膜活性,金诺芬是美国食品药品监督管理局批准的抗风湿病药物。方法采用肉汤微量稀释法对金诺芬进行真菌药敏试验。通过重氮祖林染色测试金诺芬处理的细胞活力。采用棋盘格法评价金诺芬与抗真菌药物的协同作用。通过结晶紫染色测定生物膜的抑制作用。用qRT-PCR分析和DTNB分析研究基因表达水平分析和酶活性。通过结构分析、定点诱变和微尺度热泳(MST)分析,确定了金诺芬与烟曲霉硫氧还蛋白还原酶(AfTrxR)结合的关键氨基酸残基。结果Auranofin具有杀菌活性和体外抗真菌谱,包括黄曲霉、烟曲霉、土曲霉、黑曲霉,甚至伊曲康唑(ITC)抗性烟曲霉。此外,它通过降低SomA和MedA的表达水平,对耐ITC的烟曲霉具有抗生物膜活性。此外,我们发现了金诺芬和ITC或两性霉素B对耐ITC烟曲霉的协同作用。Auranofin下调了AfTrxR的基因转录,并通过与残基C145和C148的相互作用强烈抑制了AfTrxR的酶活性。
{"title":"In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus","authors":"Peiying Chen ,&nbsp;Jing Yang ,&nbsp;Yuanling Jin ,&nbsp;Chujie Lu ,&nbsp;Zhenzhen Feng ,&nbsp;Fei Gao ,&nbsp;Yuan Chen ,&nbsp;Fuling Wang ,&nbsp;Zhuo Shang ,&nbsp;Wei Lin","doi":"10.1016/j.mycmed.2023.101381","DOIUrl":"10.1016/j.mycmed.2023.101381","url":null,"abstract":"<div><h3>Background</h3><p>Infections caused by azole-resistant <span><em>Aspergillus</em></span><span><span><span><span> are a rising public health threat with high mortality rates, high </span>treatment costs and limited available </span>antifungals, indicating an urgent need for new antifungals or strategies. Our aim was to investigate antifungal and antibiofilm activities of </span>auranofin, an FDA-approved anti-antirheumatic drug.</span></p></div><div><h3>Methods</h3><p><span><span><span>Fungal susceptibility testing for auranofin was carried out by the broth-based microdilution methods. Cell viability treated by auranofin was tested by </span>resazurin dye testing. The synergistic effect of auranofin and antifungal drugs was evaluated using checkboard assay. The inhibitory of biofilms were measured by </span>crystal violet<span><span><span> staining. Gene expression level analysis and </span>enzyme activity was investigated with qRT-PCR analysis and </span>DTNB assay. The key amino acid residues in the binding of auranofin with </span></span><em>A. fumigatus</em><span> thioredoxin reductase (</span><em>Af</em>TrxR) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays.</p></div><div><h3>Results</h3><p><span>Auranofin has fungicidal activity and </span><em>in vitro</em> antifungal spectrum including <span><em>Aspergillus flavus</em><span><span><em>, Aspergillus fumigatus, </em><em>Aspergillus terreus</em><em>, </em></span><em>Aspergillus niger</em><em>,</em></span></span><span> even itraconazole (ITC)-resistant </span><em>A. fumigatus</em>. Additionally, it has antibiofilm activities against ITC-resistant <em>A. fumigatus</em> by reducing the expression level of <em>SomA</em> and <em>MedA</em><span>. Moreover, we discovered a synergistic effect of auranofin and ITC or amphotericin B against ITC-resistant </span><em>A. fumigatus</em><span>. Auranofin downregulated the gene transcription of </span><em>Af</em>TrxR, and strongly inhibited the enzyme activity of <em>Af</em>TrxR through interacting with residues C145 and C148.</p></div><div><h3>Conclusions</h3><p>Auranofin has fungicidal and antibiofilm activities in <em>Aspergillus</em> spp. and is also a potentiator of ITC or amphotericin B <em>in vitro</em>.</p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9511374","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
Invasive cerebral aspergillosis in non-neutropenic patients: A case series from Western India 非中性粒细胞减少患者的侵袭性脑曲霉病:来自印度西部的病例系列
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2023.101380
Subhashree Samantaray , Deepak Kumar , Durga Shankar Meena , Gopal Krishana Bohra , R Akshatha , Vidhi Jain , Sarbesh Tiwari , T Balamurugan , Naresh Midha , Mahendra Kumar Garg

Purpose

Invasive cerebral aspergillosis (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021.

Methods

All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, histopathology and serum/CSF galactomannan.

Results

A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal brain abscess and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ Aspergillus antigen, Bio-Rad, France) with OD >1 and one patient had high serum galactomannan (OD >2). CSF culture grew Aspergillus species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement.

Conclusion

Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.

目的侵袭性脑曲霉菌病(ICA)是一种罕见但致命的感染,影响中性粒细胞减少免疫功能低下的患者。最近在非中性粒细胞减少的环境中也有病例报告。我们在此报告了2021年3月至10月在我们位于印度西部的三级护理中心诊断的一系列非中性粒细胞减少患者的ICA病例。方法对所有临床放射学怀疑为中枢神经系统感染的患者进行分析。收集有关临床放射学特征、诊断、治疗和结果的数据。在排除细菌、病毒和分枝杆菌的病因后,发送适当的样本进行KOH(氢氧化钾)湿悬、真菌培养、组织病理学和血清/CSF半乳甘露聚糖检查。结果共有4例患者被诊断为ICA,平均年龄43.5岁。三名患者有明显的合并症;分别用地塞米松治疗糖尿病、慢性肝病和新冠肺炎肺炎。一名患者没有已知的诱发因素。放射学上,一名患者出现额脑脓肿,两名患者出现多发皮质下高信号。根据CSF半乳甘露聚糖(Platelia™ 曲霉抗原,Bio-Rad,法国),OD>;1和1名患者具有高血清半乳甘露聚糖(OD>;2)。两名患者的CSF培养物中生长出曲霉菌。所有患者均接受伏立康唑治疗。一名患者康复,其余三名患者因表现延迟和大脑广泛受累而死亡。结论即使在非中性粒细胞减少的患者中,对脑曲霉菌病也有很高的怀疑指数。CSF半乳甘露聚糖可被认为是诊断非中性粒细胞减少环境下ICA的可靠标志物。早期诊断可以及时进行抗真菌治疗,这可能是改善疗效的关键。
{"title":"Invasive cerebral aspergillosis in non-neutropenic patients: A case series from Western India","authors":"Subhashree Samantaray ,&nbsp;Deepak Kumar ,&nbsp;Durga Shankar Meena ,&nbsp;Gopal Krishana Bohra ,&nbsp;R Akshatha ,&nbsp;Vidhi Jain ,&nbsp;Sarbesh Tiwari ,&nbsp;T Balamurugan ,&nbsp;Naresh Midha ,&nbsp;Mahendra Kumar Garg","doi":"10.1016/j.mycmed.2023.101380","DOIUrl":"10.1016/j.mycmed.2023.101380","url":null,"abstract":"<div><h3>Purpose</h3><p>Invasive cerebral aspergillosis<span> (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021.</span></p></div><div><h3>Methods</h3><p><span><span>All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, </span>treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, </span>histopathology<span> and serum/CSF galactomannan.</span></p></div><div><h3>Results</h3><p><span><span><span>A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease<span> and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal </span></span>brain abscess<span> and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ </span></span>Aspergillus antigen, Bio-Rad, France) with OD &gt;1 and one patient had high serum galactomannan (OD &gt;2). CSF culture grew </span><em>Aspergillus</em><span> species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement.</span></p></div><div><h3>Conclusion</h3><p>Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.</p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449717","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: 1
Hospital Trichosporon asahii isolates with simple architecture biofilms and high resistance to antifungals routinely used in clinical practice 医院分离的朝日毛丝虫病菌具有结构简单的生物膜和对抗真菌药物的高耐药性
IF 3.6 4区 医学 Q2 Medicine Pub Date : 2023-05-01 DOI: 10.1016/j.mycmed.2022.101356
Amanda Milene Malacrida, Jakeline Luiz Corrêa, Isabella Letícia Esteves Barros, Flávia Franco Veiga, Elton da Cruz Alves Pereira, Melyssa Negri, Terezinha Inez Estivalet Svidzinski

Infections by Trichosporon spp. are increasing worldwide and its treatment remains a challenge. Colonization of medical devices has been considered as a predisposing factor for trichosporonosis, which is related to fungal biofilm production. Thus, this study aimed to evaluate the ability of six hospital T. asahii isolates to form biofilm on abiotic surface, as well as to investigate the impact of three classic antifungals on both planktonic and biofilm forms. The fungal identification was based on macro and micromorphological characteristics, biochemical tests and confirmation by mass spectrometry assisted by the flight time desorption/ionization matrix (MALDI-TOF MS). Antifungal susceptibility assay of planktonic cells showed inhibitory and fungicidal concentrations ranging from 2.5 to 10 µg/mL for voriconazole, 2 to 8 µg/mL for fluconazole, and 1 to 4 µg/mL for amphotericin B. All T. asahii strains were able to form biofilms on the polystyrene microplates surface within 24 h, showing a simple architecture when compared with Candida spp. biofilm. On the other hand, the same antifungals did not show action in neither the inhibition of biofilm formation nor on the formed biofilm. Concluding, the present study reinforced the relevance of the MALDI-TOF MS methodology for a safe identification of T. asahii. Classic antifungals were active on the planktonic form, but not on the biofilms. All isolates formed biofilms on the polystyrene microplates and showed a simple architecture.

毛孢子虫的感染在全球范围内不断增加,其治疗仍然是一个挑战。医疗器械的定植被认为是毛孢子病的诱发因素,毛孢子病与真菌生物膜的产生有关。因此,本研究旨在评估六种医院T.asahii分离株在非生物表面形成生物膜的能力,并研究三种经典抗真菌药物对浮游生物和生物膜形式的影响。真菌鉴定基于宏观和微观形态特征、生化测试和飞行时间解吸/电离基质(MALDI-TOF MS)辅助的质谱法确认。浮游细胞的抗真菌药敏试验显示,伏立康唑的抑制和杀真菌浓度为2.5至10µg/mL,氟康唑为2至8µg/mL和两性霉素B为1至4µg/mL。与念珠菌相比,所有T.asahii菌株都能在24小时内在聚苯乙烯微孔板表面形成生物膜,显示出简单的结构。生物膜。另一方面,同样的抗真菌药物在抑制生物膜形成和对形成的生物膜都没有表现出作用。最后,本研究加强了MALDI-TOF-MS方法对T.asahii安全鉴定的相关性。经典的抗真菌药物对浮游生物形式有活性,但对生物膜没有活性。所有分离物均在聚苯乙烯微孔板上形成生物膜,结构简单。
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引用次数: 2
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Journal de mycologie medicale
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