Antifungal treatment

抗真菌治疗
  • 文章类型: Case Reports
    背景:副孢子菌病是一种被忽视的热带病,由副孢子菌属真菌引起。广泛的症状与疾病有关;然而,肺和皮肤是主要受影响的部位。这种疾病主要见于生活在拉丁美洲农村地区的人们。
    方法:我们介绍了一例对抗真菌治疗反应缓慢的严重播散性副病菌的儿科病例。三个月内,症状演变成肝脾肿大,坏死的颈部和腹部淋巴结,和脾脓肿。两性霉素B脱氧胆酸盐和伊曲康唑的临床反应缓慢,导致胸膜和腹膜腔积液,心力衰竭和休克。两性霉素B脱氧胆酸被脂质体制剂取代,没有回应。随后,治疗中加入了泼尼松,这导致了临床反应的改善。血清学副球菌抗体滴度不典型,在关键阶段滴度非常低,在恢复期显着增加。最终用两性霉素B脱氧胆酸盐清除了感染,脂质体两性霉素B和皮质类固醇的使用。副孢子菌病血清学在出院后两年无反应性。
    结论:由于副球菌细胞引发的强烈炎症反应,短时间给予小剂量泼尼松可调节炎症反应并支持抗真菌治疗.
    BACKGROUND: Paracoccidioidomycosis is a neglected tropical disease caused by fungi of the genus Paracoccidioides. A wide range of symptoms is related to the disease; however, lungs and skin are the sites predominantly affected. The disease is mostly seen in people living in rural areas in Latin America.
    METHODS: We present a pediatric case of severe disseminated paracoccidioidomycosis that slowly responded to the antifungal treatment. Within three months, symptoms evolved into hepatosplenomegaly, necrotic cervical and abdominal lymph nodes, and splenic abscess. Clinical response to amphotericin B deoxycholate and itraconazole was slow, resulting in pleural and peritoneal cavity effusions, heart failure and shock. Amphotericin B deoxycholate was replaced by the liposomal formulation, with no response. Subsequently, prednisone was added to the treatment, which led to improvement in the clinical response. Serological Paracoccidioides antibody titers were atypical, with very low titers in the critical phase and significant increase during the convalescence phase. The infection was finally cleared up with amphotericin B deoxycholate, liposomal amphotericin B and the use of corticosteroids. Paracoccidioidomycosis serology was non-reactive two years post-discharge.
    CONCLUSIONS: Due to the intense inflammatory response triggered by Paracoccidioides cells, giving low-dose prednisone for a short period of time modulated the inflammatory response and supported antifungal treatment.
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  • 文章类型: Journal Article
    体外膜氧合(ECMO)是重症监护医学中用于严重呼吸或心力衰竭患者的救命技术。这篇综述探讨了ECMO患者真菌感染的治疗和预防。根据不同抗真菌药的可用数据提出具体的治疗方案(唑类,棘白菌素,两性霉素B/脂质体两性霉素B)和侵袭性真菌感染。目前,异氟康唑和泊沙康唑拥有最支持的数据,而在ECMO中建议使用伊沙武康唑的修改剂量。棘球白素优选用于侵袭性念珠菌病。然而,由于ECMO回路中浓度损失的数据有限且各不相同,因此选择棘白菌素具有挑战性。使用两性霉素B脂质体时,由于浓度不确定和基于稀缺数据的潜在ECMO功能障碍,同样建议谨慎。我们进一步得出结论,必须进一步研究ECMO对抗真菌药物浓度的影响,以优化危重患者的给药方案。
    Extracorporeal membrane oxygenation (ECMO) is a life-saving technique used in critical care medicine for patients with severe respiratory or cardiac failure. This review examines the treatment and prophylaxis of fungal infections in ECMO patients, proposing specific regimens based on available data for different antifungals (azoles, echinocandins, amphotericin B/liposomal amphotericin B) and invasive fungal infections. Currently, isavuconazole and posaconazole have the most supported data, while modified dosages of isavuconazole are recommended in ECMO. Echinocandins are preferred for invasive candidiasis. However, choosing echinocandins is challenging due to limited and varied data on concentration loss in the ECMO circuit. Caution is likewise advised when using liposomal amphotericin B due to uncertain concentrations and potential ECMO dysfunction based on scarce data. We further conclude with the importance of further research on the impact of ECMO on antifungal drug concentrations to optimize dosing regimens in critically ill patients.
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  • 文章类型: Journal Article
    念珠菌,人类皮肤的共生居民,被认为是各种身体表面皮肤念珠菌病的原因。免疫系统较弱的人,特别是那些有免疫抑制症状的人,更容易受到这种感染。糖尿病,一种主要的代谢紊乱,已经成为诱导免疫抑制的关键因素,从而促进念珠菌定植和随后的皮肤感染。这篇全面的综述研究了糖尿病患者中不同类型的白色念珠菌引起的皮肤念珠菌病的患病率。它探讨了致病性的潜在机制,并提供了建议的预防措施和治疗策略的见解。糖尿病显著增加口腔和食道念珠菌病的易感性。此外,它可以导致女性外阴阴道念珠菌病,男性念珠菌龟头炎,糖尿病患儿的尿布念珠菌病。糖尿病个体也可能在他们的指甲上经历念珠菌感染,手和脚。值得注意的是,糖尿病似乎是肥胖者中的intertrigo综合征和义齿佩戴者中的牙周病的危险因素。总之,糖尿病和皮肤念珠菌病之间错综复杂的关系需要全面了解以制定有效的管理计划。进一步的调查和跨学科的合作努力对于解决这一多方面的挑战和发现新的治疗方法至关重要。管理和预防两种健康状况,包括开发更安全、更有效的抗真菌药物。
    Candida species, commensal residents of human skin, are recognized as the cause of cutaneous candidiasis across various body surfaces. Individuals with weakened immune systems, particularly those with immunosuppressive conditions, are significantly more susceptible to this infection. Diabetes mellitus, a major metabolic disorder, has emerged as a critical factor inducing immunosuppression, thereby facilitating Candida colonization and subsequent skin infections. This comprehensive review examines the prevalence of different types of Candida albicans-induced cutaneous candidiasis in diabetic patients. It explores the underlying mechanisms of pathogenicity and offers insights into recommended preventive measures and treatment strategies. Diabetes notably increases vulnerability to oral and oesophageal candidiasis. Additionally, it can precipitate vulvovaginal candidiasis in females, Candida balanitis in males, and diaper candidiasis in young children with diabetes. Diabetic individuals may also experience candidal infections on their nails, hands and feet. Notably, diabetes appears to be a risk factor for intertrigo syndrome in obese individuals and periodontal disorders in denture wearers. In conclusion, the intricate relationship between diabetes and cutaneous candidiasis necessitates a comprehensive understanding to strategize effective management planning. Further investigation and interdisciplinary collaborative efforts are crucial to address this multifaceted challenge and uncover novel approaches for the treatment, management and prevention of both health conditions, including the development of safer and more effective antifungal agents.
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  • 文章类型: Review
    在免疫功能正常的个体中,血液播散的曲霉脊柱炎很少见。临床,成像,这种情况的病理表现并不具体。因此,这种疾病容易误诊和漏诊。全身抗真菌治疗是曲霉菌脊柱炎的主要治疗方法。我们报告了一例免疫功能正常的患者的血液播散性杂色曲霉脊柱炎。第一次抗真菌治疗持续了4个月,但是曲霉性脊柱炎几个月后又复发了。开始第二个抗真菌治疗疗程至少1年,后续行动一直在进行。目前,没有复发。
    Blood-disseminated Aspergillus spondylitis in immunocompetent individuals is rare. The clinical, imaging, and pathological manifestations of this condition are not specific. Therefore, this disease is prone to misdiagnosis and a missed diagnosis. Systemic antifungal therapy is the main treatment for Aspergillus spondylitis. We report a case of blood-disseminated Aspergillus versicolor spondylitis in a patient with normal immune function. The first antifungal treatment lasted for 4 months, but Aspergillus spondylitis recurred a few months later. A second antifungal treatment course was initiated for at least 1 year, and follow-up has been ongoing. Currently, there has been no recurrence.
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  • 文章类型: Journal Article
    壳聚糖是衍生自几丁质脱乙酰化的阳离子多糖。这种多糖及其寡糖具有许多生物活性,由于其良好的特性,可用于多个领域,如生物降解性,生物相容性,和无毒。这篇综述探讨了壳聚糖和壳寡糖的抗真菌潜力以及它们杀死真菌细胞的活性和作用机制所需的条件。壳聚糖和壳寡糖来源,本文讨论了化学性能和应用。它还解决了真菌对人类健康和作物生产造成的威胁,以及这些糖类如何被证明对这些微生物有效。抗真菌活性的潜在机制,壳聚糖和壳寡糖在真菌细胞中触发的细胞过程,并研究了它们作为潜在抗真菌药的未来前景。
    Chitosan is a cationic polysaccharide derived from chitin deacetylation. This polysaccharide and its oligosaccharides have many biological activities and can be used in several fields due to their favorable characteristics, such as biodegradability, biocompatibility, and nontoxicity. This review aims to explore the antifungal potential of chitosan and chitooligosaccharides along with the conditions used for the activity and mechanisms of action they use to kill fungal cells. The sources, chemical properties, and applications of chitosan and chitooligosaccharides are discussed in this review. It also addresses the threat fungi pose to human health and crop production and how these saccharides have proven to be effective against these microorganisms. The cellular processes triggered by chitosan and chitooligosaccharides in fungal cells, and prospects for their use as potential antifungal agents are also examined.
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  • 文章类型: Case Reports
    喉真菌病,在具有系统免疫能力的个体中经常被忽视的情况,需要提高临床警惕性以进行准确诊断。该疾病模仿其他喉部疾病的症状,如胃食管反流,肉芽肿病,角化病,和声门恶性肿瘤,风险因素包括长期使用抗生素,吸入类固醇,和吸烟。临床上,它表现出各种症状,包括声音嘶哑,偶尔疼痛,吞咽困难,和吞咽困难.诊断包括观察角化过度,特别是当上皮内嗜中性粒细胞存在时,通过专门的染色提示进一步研究真菌元素。有效的管理包括延长全身抗真菌治疗和消除诱发因素以防止复发或治疗失败。尽管它有可能模仿一系列喉部疾病,喉真菌病仍然是一个较少考虑的鉴别诊断。一般人群中风险因素的共性加剧了这一点,包括长期使用抗生素,吸入类固醇治疗,和吸烟习惯,这可能会使个体易患喉部真菌感染。此外,高度怀疑和专业诊断技术的必要性,例如通过活检和真菌元素的专门染色鉴定上皮内嗜中性粒细胞过度角化,强调了诊断这种情况的复杂性。记录这个病例报告的理由是多方面的,主要集中在以下事实:喉真菌病在免疫功能正常的患者中很少见,导致系统性免疫功能正常的个体对喉真菌病的认识不足,以及它所带来的诊断挑战。此外,该文件旨在强调对综合治疗方法的迫切需要,包括长期的全身抗真菌治疗以及识别和消除诱发因素,确保有效管理并防止复发。
    Laryngeal mycosis, a condition often overlooked in systemically immunocompetent individuals, requires heightened clinical vigilance for accurate diagnosis. The disease mimics symptoms of other laryngeal conditions such as gastroesophageal reflux, granulomatous disease, keratosis, and glottic malignancies, with risk factors including prolonged use of antibiotics, inhaled steroids, and smoking. Clinically, it presents with variable symptoms including hoarseness, and occasionally pain, dysphagia, and odynophagia. Diagnosis involves the observation of hyperkeratosis, notably when intraepithelial neutrophils are present, prompting further investigation for fungal elements through specialized staining. Effective management encompasses prolonged systemic antifungal treatment and the elimination of predisposing factors to prevent recurrence or treatment failure. Despite its potential to mimic a range of laryngeal diseases, laryngeal mycosis remains a less considered differential diagnosis. This is compounded by the commonality of risk factors in the general population, including prolonged antibiotic use, inhaled steroid therapy, and smoking habits, which may predispose individuals to fungal infections of the larynx. Furthermore, the necessity for a high index of suspicion and specialized diagnostic techniques, such as the identification of hyperkeratosis with intraepithelial neutrophils through biopsy and specialized staining for fungal elements, underscores the complexity of diagnosing this condition. The rationale for documenting this case report is multifaceted, primarily focusing on the fact that laryngeal mycosis is rare among immunocompetent patients leading to under-recognition of laryngeal mycosis in systemically immunocompetent individuals and the diagnostic challenges it presents. Additionally, the documentation seeks to emphasize the critical need for comprehensive treatment approaches, including prolonged systemic antifungal therapy and the identification and elimination of predisposing factors, to ensure effective management and prevent recurrence.
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  • 文章类型: Journal Article
    目的:念珠菌菌血症与高死亡率相关,尤其是在危重患者中。我们的目的是确定念珠菌血症危重患者死亡率的预测因素,重点是可以改善预后的早期干预措施。
    方法:多中心回顾性研究。
    方法:这项回顾性研究于2015年至2021年在三家欧洲大学医院的重症监护病房进行。至少有一种念珠菌血培养阳性的成年患者。包括在内。不需要源控制的患者被排除。主要结果是14天死亡率。
    结果:共纳入409次念珠菌血症。大多数念珠菌与导管相关(173;41%),其次是来历不明(170;40%)。43%的发作发生感染性休克。总的来说,14天死亡率为29%。在Cox比例风险回归模型中,感染性休克(P0.001;HR2.20,CI1.38-3.50),SOFA评分≥10分(P0.008;HR1.83,CI1.18-2.86),和先前的SARS-CoV-2感染(P0.003;HR1.87,CI1.23-2.85)与14天死亡率相关,而联合早期适当的抗真菌治疗和来源控制(P<0.001;HR0.15,CI0.08-0.28),与没有早期适当抗真菌治疗或来源控制的患者相比,没有适当抗真菌治疗的早期来源控制(P<0.001;HR0.23,CI0.12-0.47)与更好的生存率相关。
    结论:在念珠菌病危重患者中,早期源控制与更好的预后相关。
    OBJECTIVE: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis.
    METHODS: Multicenter retrospective study.
    METHODS: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality.
    RESULTS: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38-3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18-2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23-2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08-0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12-0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control.
    CONCLUSIONS: Early source control was associated with better outcome among candidemic critically ill patients.
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  • 文章类型: Journal Article
    欧洲医学真菌学联合会(ECMM)由于侵袭性真菌感染(FI)的激增而形成,2016年启动了卓越中心计划,以指导利益相关者进入领先的医学真菌学网站。本报告重点介绍科隆ECMM卓越中心,2017年被认可为钻石公司积极参与全球事务。该中心通过电子邮件和电话提供免费咨询,在24小时内对危及生命的FI做出反应,收集原产地数据,病原体,感染细节,还有更多.两年多了,全球共收到189项请求,主要来自德国(85%),主要涉及曲霉属。,Mucorales,和念珠菌属。4%的病例发生真菌混合感染。该中心的服务有效地解决了国际金融机构的挑战,倡导一项涵盖所有ECMM卓越中心的全面研究,以加强全球真菌学护理。积极拓展咨询平台至关重要,未来的分析需要评估专家建议对患者预后的影响。
    The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center\'s service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice\'s impact on patient outcomes.
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  • 文章类型: Journal Article
    世界卫生组织(WHO)最近公布了一份真菌优先病原体名单,包括白色念珠菌和C.auris。念珠菌耐药性的增加引起了人们的关注,考虑到只有四类药物的可用性。WHO正在寻找具有不同目标和作用机制的新型药剂类别。靶向念珠菌谷冬酶以控制内在细胞死亡可能为侵袭性念珠菌病提供新的治疗机会。在这次审查中,我们提供了念珠菌细胞死亡的现有证据,描述念珠菌谷冬酶,并商量了假丝酵母β-胱天蛋白酶的潜力,为其提供一个新的特异性靶点。靶向念珠菌细胞死亡具有良好的科学原理,因为许多市售抗真菌剂的杀菌活性是介导的,其中,细胞死亡触发。但是现有的抗真菌药物都没有特异性激活念珠菌的β-半胱氨酸蛋白酶,使此靶标成为非易感分离株的新治疗机会。预计基于真菌的激活的抗真菌药物将具有广泛的作用,正如在许多真菌中已经描述的,包括丝状真菌。考虑到这种原始的作用机制,将这些新的抗真菌候选药物与现有的抗真菌药物结合起来可能会引起极大的兴趣。这种方法将有助于避免抗真菌耐药性的发展,在念珠菌中尤其增加。
    The World Health Organization (WHO) recently published a list of fungal priority pathogens, including Candida albicans and C. auris. The increased level of resistance of Candida is raising concern, considering the availability of only four classes of medicine. The WHO is seeking novel agent classes with different targets and mechanisms of action. Targeting Candida metacaspases to control intrinsic cell death could provide new therapeutic opportunities for invasive candidiasis. In this review, we provide the available evidence for Candida cell death, describe Candida metacaspases, and discuss the potential of Candida metacaspases to offer a new specific target. Targeting Candida cell death has good scientific rationale given that the fungicidal activity of many marketed antifungals is mediated, among others, by cell death triggering. But none of the available antifungals are specifically activating Candida metacaspases, making this target a new therapeutic opportunity for non-susceptible isolates. It is expected that antifungals based on the activation of fungi metacaspases will have a broad spectrum of action, as metacaspases have been described in many fungi, including filamentous fungi. Considering this original mechanism of action, it could be of great interest to combine these new antifungal candidates with existing antifungals. This approach would help to avoid the development of antifungal resistance, which is especially increasing in Candida.
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  • 文章类型: Case Reports
    该报告描述了子宫胚真菌病的罕见发生,在北美流行的皮肤芽胞杆菌感染的非典型全身表现。专注于一名51岁的有免疫能力的女性,表现出腹痛和不规则的阴道出血,它强调了反映常见妇科疾病的症状所带来的复杂诊断障碍。尽管记录的病例不到10例,子宫受累的稀有性凸显了增加临床怀疑的必要性。多方面的诊断策略综合了风险因素,旅行史,成像,和组织病理学检查。强调由妇科医生主持的多学科治疗,病理学家,和传染病专家,抗真菌药物的利用,尤其是伊曲康唑,是关键的。解决文献的稀缺性和这种疾病与普遍疾病的临床相似性,进一步的研究对于设计定制的子宫胚菌病诊断和治疗方案至关重要。这项研究通过提供对几乎没有记载的疾病的批判性见解,丰富了现有的文献。贡献了对临床理解和管理策略至关重要的新观点。
    The report delineates the rare occurrence of uterine blastomycosis, an atypical systemic presentation of Blastomyces dermatitidis infection prevalent in North America. Focused on a 51-year-old immunocompetent female displaying abdominal pain and irregular vaginal bleeding, it underscores the intricate diagnostic hurdles posed by symptoms mirroring common gynecological conditions. Despite fewer than 10 recorded cases, the rarity of uterine involvement highlights the imperative for heightened clinical suspicion. The multifaceted diagnostic strategy integrates risk factors, travel history, imaging, and histopathological examinations. Emphasizing a multidisciplinary treatment helmed by gynecologists, pathologists, and infectious disease specialists, the utilization of antifungal agents, notably itraconazole, is pivotal. Addressing the scarcity of literature and the condition\'s clinical resemblance to prevalent ailments, further research becomes paramount in devising tailored diagnostic and treatment protocols for uterine blastomycosis. This study enriches the existing literature by providing critical insights into a scarcely documented condition, contributing novel perspectives essential for clinical understanding and management strategies.
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