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Anfotericina B liposomal: farmacología clínica, farmacocinética y farmacodinamia 脂质体两性霉素B:临床药理学、药代动力学和药效学
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.02.004
José Ramón Azanza Perea

Liposomal amphotericin B is a lipid formulation of the antifungal drug amphotericin B with some distinguishing characteristics in its pharmacological behavior that entail some clinical differences of great interest. The significant improvement in the systemic and renal tolerability is one of them. This fact is related to the great stability of the liposome, promoted by its negative charge, the presence of cholesterol and the remarkable thermo-stability of the remaining lipids that compose it. In this situation, amphotericin B seems to be released from the liposome not spontaneously but when the liposome binds to the ergosterol in the fungal cell membrane. For this reason, there is almost no free amphotericin B in plasma or tissues, although it seems that its availability is greater when there is fungal infection. As a consequence, when the pharmacokinetic behavior is studied, the concentration and availability of liposomal amphotericin B are very high, and its volume of distribution is reduced in comparison with the other formulations.

脂质体两性霉素B是抗真菌药物两性霉素B的脂质制剂,其药理行为具有一些独特的特征,引起了一些临床差异的极大兴趣。系统和肾脏耐受性的显著改善就是其中之一。这一事实与脂质体的巨大稳定性有关,这种稳定性是由它的负电荷、胆固醇的存在和组成它的剩余脂质的显著的热稳定性所促进的。在这种情况下,两性霉素B似乎不是自发地从脂质体中释放出来,而是当脂质体与真菌细胞膜中的麦角甾醇结合时释放出来的。因此,血浆或组织中几乎没有游离两性霉素B,尽管在真菌感染时它的可用性似乎更大。因此,当研究药代动力学行为时,两性霉素B脂质体的浓度和可用性非常高,与其他制剂相比,其分布体积减小。
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引用次数: 1
Anfotericina B liposomal: treinta años de una herramienta muy eficaz para el tratamiento de las micosis invasoras 脂质体两性霉素B:三十年来治疗侵袭性真菌病的非常有效的工具
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.04.007
Javier Pemán , Guillermo Quindós
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引用次数: 1
Relevancia de la anfotericina B liposomal en el tratamiento de las infecciones fúngicas invasoras en pacientes oncohematológicos 脂质体两性霉素B在肿瘤血液学患者侵袭性真菌感染治疗中的相关性
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.03.001
Carolina García-Vidal , Lourdes Vázquez , Isidro Jarque

Liposomal amphotericin B (L-AmB) has been a key cornerstone for the management of invasive fungal infections (IFI) caused by a wide array of molds and yeasts during the last three decades. Multiple studies performed over this period have generated a large body of evidence on its efficacy and safety, becoming the main antifungal agent in the management of IFI in patients with hematologic malignancies in several not mutually exclusive clinical settings. First, L-AmB is the most commonly used antifungal agent in patients undergoing intensive chemotherapy for acute leukemia and high-risk myelodysplastic syndrome, as well as in hematopoietic stem cell transplant recipients. Additionally, due to the administration of newer targeted therapies (such as monoclonal antibodies or small molecule inhibitors), opportunistic mold infections are increasingly being reported in patients with hematologic malignancies usually considered low-risk for IFI. These agents usually have a high drug-drug interaction potential, being triazoles, commonly used for antifungal prophylaxis, included. Finally, patients developing breakthrough IFI because of either subtherapeutic concentrations of antifungal prophylactic drugs in blood or selection of resistant strains, require broad spectrum antifungal therapy, usually with an antifungal of a different class. In both situations, L-AmB remains as the best option for early antifungal therapy.

在过去的三十年中,脂质体两性霉素B (L-AmB)已成为管理由多种霉菌和酵母引起的侵袭性真菌感染(IFI)的关键基石。在此期间进行的多项研究已经产生了大量关于其有效性和安全性的证据,在一些并不相互排斥的临床环境中,它成为血液系统恶性肿瘤患者IFI治疗的主要抗真菌药物。首先,L-AmB是急性白血病和高危骨髓增生异常综合征患者接受强化化疗以及造血干细胞移植患者最常用的抗真菌药物。此外,由于新的靶向治疗(如单克隆抗体或小分子抑制剂)的使用,机会性霉菌感染在血液恶性肿瘤患者中越来越多地被报道,通常被认为是IFI的低风险。这些药物通常具有很高的药物相互作用潜力,包括三唑类,通常用于抗真菌预防。最后,由于血液中抗真菌预防性药物浓度低于治疗水平或选择耐药菌株而出现突破性IFI的患者需要广谱抗真菌治疗,通常使用不同类别的抗真菌药物。在这两种情况下,L-AmB仍然是早期抗真菌治疗的最佳选择。
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引用次数: 4
La infección fúngica en el paciente pediátrico inmunodeprimido 小儿免疫功能低下患者的真菌感染
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.04.005
Marta González-Vicent , José Tomás Ramos-Amador

In recent years, immunodeficiency condition has experienced a rise among children, who are at risk of invasive fungal infections (IFI) due to their health condition. Cancer, non-malignant hematological diseases, as primary immunodeficiencies, hematopoietic stem cell transplantation (HSCT), extreme prematurity, or critically ill condition in Pediatric Intensive Care Unit (PICU) are some immunosuppressive situations in children. The use of oncologic therapies, including immunotherapy and monoclonal antibodies, for the treatment of the aforementioned health conditions has led to an increase in morbidity and mortality rates of IFI in children.

The underlying diseases and their management, comorbidities, the diagnostic tests used (both molecular and imaging), as well as the treatment used can be significantly different between adult patients and children admitted to PICU or with cancer. In pediatrics, the treatment of IFI is based primarily on pharmacokinetic studies performed in adults. In higher risk patients prophylaxis should be considered and, in the case of an IFI diagnosis, an antifungal treatment should be administered as early as possible, supported by the reversion of the immune dysfunction and surgery when appropriate.

近年来,免疫缺陷状况在儿童中有所上升,由于他们的健康状况,他们面临侵袭性真菌感染(IFI)的风险。癌症、非恶性血液系统疾病,如原发性免疫缺陷、造血干细胞移植(HSCT)、极度早产或儿科重症监护病房(PICU)危重症,都是儿童免疫抑制的一些情况。使用肿瘤疗法,包括免疫疗法和单克隆抗体治疗上述健康状况,导致儿童患IFI的发病率和死亡率增加。潜在疾病及其管理、合并症、使用的诊断测试(分子和成像)以及使用的治疗方法在PICU收治的成人患者和儿童患者或癌症患者之间可能存在显著差异。在儿科,IFI的治疗主要基于在成人中进行的药代动力学研究。在高风险患者中应考虑预防,在IFI诊断的情况下,应尽早给予抗真菌治疗,并辅以免疫功能障碍的恢复和适当的手术。
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引用次数: 2
Tratamiento antifúngico individualizado en el paciente crítico con infección fúngica invasora 侵袭性真菌感染危重患者个体化抗真菌治疗
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.04.006
Rafael Zaragoza , Emilio Maseda , Javier Pemán

Invasive candidiasis (IC) is the most common invasive fungal infection (IFI) affecting critically ill patients, followed by invasive pulmonary aspergillosis (IPA). International guidelines provide different recommendations for a first-line antifungal therapy and, in most of them, echinocandins are considered the first-line treatment for IC, and triazoles are so for the treatment of IPA. However, liposomal amphotericin B (L-AmB) is still considered a second-line therapy for both clinical entities. Although in the last decade the management of IFI has improved, several controversies persist. The antifungal drugs currently available may have a suboptimal activity, or be wrongly used in certain IFI involving critically ill patients. The aim of this review is to analyze when to provide individualized antifungal therapy to critically ill patients suffering from IFI, emphasizing the role of L-AmB. Drug-drug interactions, the clinical status, infectious foci (peritoneal candidiasis is discussed), the fungal species involved, and the need of monitoring the concentration of the antifungal drug in the patient are considered.

侵袭性念珠菌病(IC)是最常见的侵袭性真菌感染(IFI),影响危重患者,其次是侵袭性肺曲霉病(IPA)。国际指南对一线抗真菌治疗提供了不同的建议,在大多数指南中,棘白菌素被认为是IC的一线治疗,而三唑则被认为是治疗IPA的一线治疗。然而,脂质体两性霉素B (L-AmB)仍被认为是这两种临床实体的二线治疗。尽管在过去十年中,国际金融机构的管理有所改善,但仍存在一些争议。目前可用的抗真菌药物可能具有次优活性,或者在某些涉及危重患者的IFI中错误使用。本综述的目的是分析何时为IFI危重患者提供个体化抗真菌治疗,强调L-AmB的作用。考虑到药物相互作用,临床状况,感染灶(讨论腹膜念珠菌病),所涉及的真菌种类,以及监测患者抗真菌药物浓度的需要。
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引用次数: 4
Evolución de la infección fúngica invasora en los últimos 30 años 过去30年侵袭性真菌感染的演变
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.03.003
José Tiago Silva , Isabel Ruiz-Camps , José María Aguado

Clinical mycology is in continuous development. The appearance of new clinical guidelines has made it possible to improve the approach to opportunistic fungal infections, especially in immunosuppressed patients (oncohematological and/or transplant recipients). At the same time, the development of new diagnostic tools and new antifungals with a greater spectrum of action and fewer side effects have led to faster diagnoses and treatments that are more effective. Along with these advances, there has been a change in the epidemiology of invasive fungal infection (IFI), with the appearance of new patients (e.g., COPD, liver cirrhosis, post-influenza) and new microorganisms (Candida auris, Lomentospora prolificans, mucorales), and resistant fungi (isolates of Aspergillus resistant to azoles) which the clinician must take into account when choosing the treatment of a patient with an IFI. In this paper we will briefly review the advances in recent decades and the emerging problems.

临床真菌学是一个不断发展的学科。新的临床指南的出现使得改善机会性真菌感染的方法成为可能,特别是在免疫抑制患者(血液肿瘤和/或移植受者)中。与此同时,新的诊断工具和作用范围更广、副作用更少的新型抗真菌药物的开发,导致了更快的诊断和更有效的治疗。随着这些进展,侵袭性真菌感染(IFI)的流行病学也发生了变化,出现了新的患者(例如,慢性阻塞性肺病、肝硬化、流感后)和新的微生物(耳念珠菌、增殖性lolotospora prolificans、mucorales),以及耐药真菌(曲霉菌对唑类药物耐药的分离株),临床医生在选择IFI患者的治疗时必须考虑到这些。在本文中,我们将简要回顾近几十年来的进展和新出现的问题。
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引用次数: 2
Antifúngicos de uso sistémico 全身使用的抗真菌药物
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.04.004
Inmaculada Quiles-Melero, Julio García-Rodríguez

Las infecciones fúngicas invasivas han aumentado en las últimas décadas y las opciones terapéuticas para combatirlas son limitadas. Los agentes antifúngicos empleados son útiles y tienen óptima actividad in vitro, pero pierden eficacia debido al desarrollo de resistencias por parte de los hongos. El incremento de especies con resistencia primaria o secundaria a algunos fármacos antifúngicos ha generado la necesidad de desarrollar nuevas formulaciones o recurrir a alternativas como la combinación de fármacos. En este artículo se revisará el espectro de actividad de las principales familias de antifúngicos, polienos, azoles, equinocandinas, 5-fluorocitosina y nuevos fármacos antifúngicos, así como los mecanismos de resistencia descritos contra los mismos.

Invasive fungal infections have increased over the last decades and the therapeutic choices to treat them are limited. The antifungal agents currently available are useful and have optimal in vitro activity; however, their activity can be lowered due to the development of fungal resistance. The increase in primary or secondary resistance to some antifungal drugs has led to the search of alternatives such as the combination of drugs or the development of new antifungals. In this paper, the activity of the main families of antifungal drugs, polyenes, azoles, echinocandins, 5-fluorocytosine and other new antifungal drugs, are reviewed. The main resistance mechanisms developed by fungi are also described.

在过去的几十年里,侵袭性真菌感染有所增加,对抗它们的治疗选择有限。所使用的抗真菌药物是有用的,在体外具有最佳的活性,但由于真菌产生耐药性而失去效力。对一些抗真菌药物具有一级或二级耐药性的物种的增加产生了开发新配方或使用替代药物(如联合药物)的需求。本研究的目的是评估抗真菌药物的抗真菌活性,并确定抗真菌药物的抗真菌活性,以及抗真菌药物的耐药性机制。侵袭性真菌感染在过去几十年中有所增加,治疗它们的治疗选择有限。目前可用的抗真菌药物是有用的,具有最佳的体外活性;然而,由于真菌抗性的发展,它们的活动可能会减少。= =地理= =根据美国人口普查,这个县的面积为,其中土地和(1.1%)水。本文回顾了主要的抗真菌药物家族,如多烯类、唑类、棘球绦虫类、5-氟催产素和其他新型抗真菌药物的活性。= =地理= =根据美国人口普查,这个县的面积为。
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引用次数: 3
Seguridad clínica de la anfotericina B liposomal 脂质体两性霉素B的临床安全性
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-04-01 DOI: 10.1016/j.riam.2021.02.001
Borja Suberviola

This article reviews the safety profile of liposomal amphotericin B, emphasizing the renal toxicity; the risk factors for its presentation, incidence, severity, and potential reversibility are expounded.

本文综述了两性霉素B脂质体的安全性,强调其肾毒性;阐述了其表现、发生率、严重程度和潜在可逆性的危险因素。
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引用次数: 3
Exophiala dermatitidis as a cause of central line associated bloodstream infection in an infant: Case report and literature review 外表皮皮炎是婴儿中央线相关血流感染的原因:病例报告和文献回顾
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-01-01 DOI: 10.1016/j.riam.2020.09.004
Anil Kumar , Aswathy Nandakumar , Sajitha Nair , Ashutosh Singh , Nandita Shashindran , Swathy Thulasidharan , Kiran Subhash , Arya Ramachandran , Anuradha Chowdhary

Background

Exophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described.

Case report

Clinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06 mg/l), voriconazole (0.03 mg/l) and itraconazole (0.03 mg/l) showed very low MICs when compared to fluconazole (4 mg/l)

Conclusions

As we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment.

背景:嗜皮菌性皮炎是一种真菌,已知可引起浅表、皮下、皮肤和深部感染,很少引起中枢性血流感染(CLABSI)。一例CLABSI由于在一个婴儿皮炎e描述。病例报告:临床和实验室资料摘自患者病历和实验室记录。通过表型鉴定和核糖体DNA ITS区和LSU区测序,鉴定该分离物为皮炎杆菌。Medline检索回顾了所有由皮炎E.引起的CLABSI病例。与氟康唑(4 mg/l)相比,泊沙康唑(0.06 mg/l)、伏立康唑(0.03 mg/l)和伊曲康唑(0.03 mg/l)的mic值非常低。结论文献中未见婴儿皮炎e型所致CLABSI病例,本文报道第一例。测序是准确鉴定该物种的必要方法。迅速切除中央静脉导管,然后用两性霉素B或唑治疗,似乎是最有效的治疗方法。
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引用次数: 6
Problemas clínicos en Micología Médica: problema número 55 医学真菌学的临床问题:第55期
IF 1.9 4区 生物学 Q3 Medicine Pub Date : 2021-01-01 DOI: 10.1016/j.riam.2020.10.004
Mercedes Romero , Fernando Messina , Roxana Depardo , Emmanuel Marín , Alicia Arechavala , Nicolás Lista , Alejandra Rodríguez , Gabriela Santiso

A 31-year-old woman, with signs of HIV infection (oral thrush, weight loss, asthenia) presented to our hospital with dyspnea and fever. A rapid HIV test yielded a positive result, and cryptococcal capsular antigen was detected in serum. In the mycological study of the clinical respiratory samples, yeasts compatible with Cryptococcus were observed under light microscope in a wet mount; structures compatible with Pneumocystis jirovecii were also observed in Giemsa stain. Treatment for both pathologies was prescribed but, unfortunately, the patient died 7 days after. The finding of two etiologic agents in the same clinical picture is rare but not exceptional, and it always must be considered in immunocompromised hosts.

一名31岁女性,有HIV感染症状(鹅口疮、体重下降、虚弱),以呼吸困难、发热就诊。快速HIV检测结果为阳性,血清中检测到隐球菌荚膜抗原。在临床呼吸道样本的真菌学研究中,在湿mount光镜下观察到与隐球菌相容的酵母;吉姆萨染色也观察到与氏肺囊虫相容的结构。对这两种病症进行了治疗,但不幸的是,患者在7天后死亡。在同一临床图像中发现两种病因是罕见的,但并不例外,在免疫功能低下的宿主中必须加以考虑。
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引用次数: 1
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Revista Iberoamericana De Micologia
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