amphotericin B

两性霉素 B
  • 文章类型: English Abstract
    Amphotericin B (AmB) is a broad-spectrum and potent polyene antifungal drug for the treatment of invasive fungal diseases (IFDs). Currently, amphotericin B deoxycholate (AmB-D) and three AmB lipid formulations, namely liposomal amphotericin B (L-AmB), amphotericin B colloidal dispersion (ABCD), and amphotericin B lipid complex (ABLC) are available for clinical use. In view of clinical concerns and misperceptions in the selection of different formulations of AmB, the present consensus summarized their pharmaceutical characteristics, antifungal mechanism, pharmacokinetics/phamacodynamics, drug interactions, indications, dosage, local administration, and adverse reactions based on the latest clinical research evidence, guidelines, and clinical experience. This consensus also recommends formulation selection and dosage adjustment for the treatment of target IFDs and in special populations, thereby providing expert consensus for clinical decision-making and standardized application of AmB.
    两性霉素B(AmB)是临床治疗侵袭性真菌病(IFD)广谱强效的多烯类抗真菌药物。目前已有两性霉素B脱氧胆酸盐(AmB-D)及3种AmB脂质剂型,包括两性霉素B脂质体(L-AmB)、两性霉素B胶状分散体(ABCD)和两性霉素B脂质复合物(ABLC)可供临床使用。根据临床在选择AmB不同剂型方面关注与困惑的问题,本共识结合国内外最新临床研究证据、指南、共识以及临床经验,针对AmB 4种不同剂型的药剂学特点、抗真菌作用机制、药代动力学/药效学、药物相互作用、适应证、用法用量、局部用药、不良反应防治等特点,明确AmB在IFD目标治疗的剂型与剂量选择,并对特殊人群的用法用量加以规范,为该类药物的临床决策与合理应用提供指导意见。.
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  • 文章类型: English Abstract
    重症患者COVID-19相关性肺曲霉病(CAPA)的发病率和死亡率较高。尽管COVID-19相关毛霉菌病(CAPM)相对罕见,其严重程度和经常延迟诊断或误诊导致其高死亡率。危重患者CAPA和CAPM的诊断和治疗具有挑战性。早期诊断和标准化治疗是获得良好结果的两个最重要因素。因此,组织了一个由中国胸科学会和中国胸科医师协会重症监护小组专家组成的工作组,根据目前的医学证据和临床实践,以提高危重患者CAPA和CAPM的临床治疗能力。工作组根据文献和临床实践经验起草了初步文本。经过两轮讨论,最后提出了16项建议,将推荐强度分为推荐,建议和不推荐。-胸部图像和支气管镜的利用1.胸部CT,而不是胸部X光,建议可能的CAPA或CAPM患者为支气管镜检查提供诊断证据和定位以获取微生物标本。不能仅根据胸部CT的阳性体征来诊断CAPA。对于可能患有CAPM.2的患者,建议使用胸部造影CT或肺动脉CT(CTPA)。在可能的CAPA或CAPM的情况下,建议尽快进行支气管镜检查和收集BALF以进行微生物学检查。·微生物检验的选择策略3.显微镜检查,文化,曲霉菌的GM检测和PCR。BALF的建议用于可能的CAPA患者。对于可能的CAPM,建议对BALF进行真菌染色和培养。建议在重症患者和可能的CAPM中选择适当的标本进行分子生物学检测。-诊断判决书4.建议将修订的ECMM/ISHAM共识声明作为CAPA的诊断标准,并建议将Delphi共识声明作为CAPM的诊断标准。-抗真菌治疗的适当时间5。对于患有严重COVID-19的患者,尤其是具有CAPA6危险因素的患者,建议使用两性霉素B或其脂质体进行CAPA的预防性治疗。对于可能的CAPA,建议尽快开始经验性抗曲霉治疗,并同时获得曲霉菌的微生物证据。严重COVID-19患者不推荐CAPM预防性治疗。建议尽早开始对可能的CAPM进行经验性治疗,和微生物证据应同时获得。-抗真菌剂的临床应用9.建议伏立康唑或伊沙康康唑作为CAPA的初始治疗。两性霉素B脂质体被建议作为CAPM的初始治疗。对于肾功能不全或两性霉素B脂质体不耐受/不可用的患者,可选择使用艾沙康唑或泊沙康唑。在患有气管支气管炎的CAPA患者中,除全身抗真菌药物外,还建议吸入抗真菌药物。11.联合治疗不推荐作为CAPA的初始治疗,但可以用作挽救治疗策略。建议使用三唑或两性霉素B与卡泊芬净或米卡芬净组合;而不建议使用两性霉素B与三唑组合。对于有广泛病变的CAPM患者,快速进展或一般情况差,建议将两性霉素B脂质体与伊沙康康唑或泊沙康唑联合使用。-反应评估和治疗持续时间12.建议根据临床症状/体征全面评估治疗反应,患者的影像学和微生物学检查。CAPA可以结合血清GM.13的动态变化进行评估。CAPA的推荐治疗持续时间为至少6-12周。CAPM建议至少3-6个月的总课程,应根据4-6周静脉治疗的反应考虑序贯治疗。-如何调整抗炎治疗14.在严重COVID-19合并可能或可能的丝状真菌感染的患者中,建议停止或适当减少抗炎治疗,考虑到疾病过程中感染和炎症的严重程度。在这些患者中不建议使用基于糖皮质激素的巴利替尼和/或托珠单抗的组合。-如何治疗潜在的疾病15.在糖尿病患者中,建议严格控制血糖。长期使用糖皮质激素和/或免疫抑制剂的患者,建议降低免疫抑制的强度。建议使用粒细胞集落刺激因子来改善由于各种原因导致的粒细胞缺乏患者的循环粒细胞水平。-什么时候应该考虑手术16。在CAPA患者中,不建议手术,除非大血管,心包,或者涉及胸壁,或者患者有反复或大咯血。对于CAPM患者,建议诊断后早期手术切除病灶。手术是严重COVID-19患者的高风险手术,建议多学科团队对此进行讨论。
    经验证COVID-中医中医中医中医中医中医中医中医中医(CAPA)的康复病症,中医中医中医中医高,中医中医中医中医中医中医中医中医中医高。而中医中医中医中医中医嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯嗯
    The incidence and mortality of COVID-19 associated pulmonary aspergillosis (CAPA) are high in critically ill patients. Although COVID-19 associated mucormycosis (CAPM) is relatively rare, its severity and often a delayed diagnosis or misdiagnosis lead to its high mortality. The diagnosis and treatment of CAPA and CAPM in critically ill patients are challenging. Early diagnosis and a standardized therapy are the two most important factors for a good outcome. Therefore, a working group of experts from Chinese Thoracic Society and Chinese Association of Chest Physicians Critical Care Group was organized to develop this consensus based on the current medical evidence and clinical practice, in order to improve the ability of clinical treatment for critically ill patients with CAPA and CAPM. The working group drafted a preliminary text based on the literature and clinical practice experience. Following two rounds of discussion, 16 final recommendations were made, with the recommendation strength divided into recommend, suggest and not recommend.-Utilization of chest images and bronchoscopy1. Chest CT, rather than chest X-ray, is recommended for possible CAPA or CAPM patients to provide diagnostic evidence and localization for bronchoscopy to obtain microbiological specimens. A diagnosis of CAPA could not be made on the basis of positive signs on chest CT alone. Chest contrast CT or pulmonary artery CT (CTPA) is recommended in patients with probable CAPM.2. In the case of possible CAPA or CAPM, it is recommended that bronchoscopy and BALF collection for microbiological examinations be pereformed as soon as possible.-The selection strategies of microbiological examinations3. Microscopic examination, culture, GM testing and PCR for aspergillus Spp. of BALF are recommended in patients with probable CAPA. Fungal staining and culture of BALF are suggested for possible CAPM. Selected appropriate specimens for molecular biological detection are suggested in critically ill patients and possible CAPM.-Diagnostic critieria4. The revised ECMM/ISHAM consensus statement is recommended as the diagnostic criteria for CAPA and the Delphi consensus statement is recommended as the diagnostic criteria for CAPM.-Appropriate time for antifungal therapy5. Prophylactic therapy of CAPA with amphotericin B or its liposomes is suggested for patients with severe COVID-19, especially those with risk factors for CAPA.6. It is recommended to start the empirical anti-Aspergillus therapy as soon as possible for possible CAPA, and obtain the microbiological evidence for aspergillosis at the same time.7. Prophylactic therapy for CAPM is not recommended for severe COVID-19 patients.8. Early initiation of empirical therapy for possible CAPM is recommended, and microbiological evidence should be obtained at the same time.-Clinical applications for antifungal agents9.Voriconazole or isavuconazole are recommended as initial treatment for CAPA. Amphotericin B liposomes are suggested as the initial treatment for CAPM. Isavuconazole or posaconazole may be an option in patients with renal insufficiency or amphotericin B liposome intolerance/unavailability.10. In CAPA patients with tracheobronchitis, antifungal drug inhalation is recommended in addition to systemic antifungal medication.11. Combination therapy is not recommended as initial therapy for CAPA, but may be used as a salvage therapy strategy. Triazole or amphotericin B in combination with caspofungin or micafungin is recommended; whereas amphotericin B in combination with triazole is not recommended. For CAPM patients with extensive lesions, rapid progression or poor general condition, a combination of amphotericin B liposome with isavuconazole or posaconazole is suggested.-Response assessment and treatment duration12. It is recommended that treatment response be assessed comprehensively according to the clinical symptoms/signs, imaging and microbiological examination of patients. CAPA can be evaluated in combination with the dynamic change in serum GM.13. The recommended treatment duration of CAPA is at least 6-12 weeks. A total course of at least 3-6 months is suggested for CAPM, and the sequential treatment should be considered according to the response to 4-6 weeks of intravenous therapy.-How to adjust the anti-inflammatory therapy14. In patients with severe COVID-19 combined with possible or probable filamentous fungal infection, it is suggested that of anti-inflammatory therapy be stopped or reduced appropriately, taking into account of the severity of the infection and inflammation of the disease course. The combination of baritinib and/or tozzizumab based on glucocorticoids is not suggested in these patients.-How to treat the underlying diseases15. In patients with diabetes, strict glycaemic control is suggested. In patients with long-term use of glucocorticoids and/or immunosuppressants, it is suggested to reduce the intensity of immunosuppression. Granulocyte colony-stimulating factor is suggested to use to improve the circulating granulocyte levels in patients with granulocyte deficiency due to various causes.-When an operation should be considered16. In patients with CAPA, surgery is not recommended unless large blood vessels, pericardium, or chest wall are involved, or the patient has recurrent or massive hemoptysis. For CAPM patients, early surgical removal of lesions after diagnosis is recommended. Surgery is a high-risk procedure in patients with severe COVID-19, and a multidisciplinary team discuss is suggested.
    重症COVID-19相关肺曲霉病(CAPA)的发病率及病死率均较高。而新型冠状病毒感染相关肺毛霉病(CAPM)虽然相对少见,但疾病本身的严重性加之误诊及诊断延误也导致其病死率居高不下。目前,重症CAPA及CAPM的诊断及治疗均面临巨大挑战。如何早期诊断并规范治疗是救治成功的关键。因此,中国医师协会呼吸医师分会危重症学组与中华医学会呼吸病学分会危重症学组发起并组织相关领域专家,基于目前的循证医学证据及临床实践经验,撰写本共识,以期提高重症CAPA及CAPM患者的临床救治。工作组结合文献及临床实践经验,形成共识的初步文本。经两次讨论会,最终确定16条核心推荐意见并给出推荐强度,分为推荐、建议及不推荐。.
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  • 文章类型: English Abstract
    Amphotericin B (AmB) is an antifungal drug with the broadest spectrum and the most robust antifungal activity in clinical practice. Although there are many kinds of lipid formulations which significantly reduce the toxicity and side effects of amphotericin B deoxycholate (AmBd), AmBd will still play an important clinical role in China for a long time since lipid formulations are substantially more expensive. To standardize the clinical application of AmBd, well-known experts in this field were invited to reach a consensus on the antifungal properties, pharmacokinetic characteristics, dosage regimen, clinical application, prevention and treatment of adverse reactions of AmBd.
    两性霉素B(AmB)是目前临床上抗真菌谱最广,活性最强的抗真菌药物,尽管有多种脂质制剂上市,极大地降低了两性霉素B脱氧胆酸盐(AmBd)的不良反应,但价格昂贵。因此,在我国AmBd在未来很长的一段时间内仍有重要的临床地位。为了提高AmBd临床疗效,降低毒副反应,编写组邀请国内该领域知名专家就AmBd的抗菌特性、药动学特点、给药方案、临床应用、不良反应防治等方面达成了共识,规范AmBd的临床应用。.
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  • 文章类型: Practice Guideline
    The Taiwan Acute Kidney Injury (AKI) Task Force conducted a review of data and developed a consensus regarding nephrotoxins and AKI. This consensus covers: (1) contrast-associated AKI; (2) drug-induced nephrotoxicity; (3) prevention of drug-associated AKI; (4) follow up after AKI; (5) re-initiation of medication after AKI. Strategies for the avoidance of contrast media related AKI, including peri-procedural hydration, sodium bicarbonate solutions, oral N-acetylcysteine, and iso-osmolar/low-osmolar non-ionic iodinated contrast media have been recommended, given the respective evidence levels. Regarding anticoagulants, both warfarin and new oral anticoagulants have potential nephrotoxicity, and dosage should be reduced if renal pathology exam proves renal injury. Recommended strategies to prevent drug related AKI have included assessment of 5R/(6R) reactions - risk, recognition, response, renal support, rehabilitation and (research), use of AKI alert system and computerized decision support. In terms of antibiotics-associated AKI, avoiding concomitant administration of vancomycin and piperacillin-tazobactam, monitoring vancomycin trough level, switching from vancomycin to teicoplanin in high-risk patients, and replacing conventional amphotericin B with lipid-based amphotericin B have been shown to reduce drug related AKI. With respect to non-steroidal anti-inflammatory drug associated AKI, it is recommended to use these drugs cautiously in the elderly and in patients receiving renin-angiotensin-aldosterone system inhibitors/diuretics triple combinations.
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  • 文章类型: Journal Article
    严重急性呼吸综合征冠状病毒2对气道上皮造成直接损害,使曲霉入侵。关于COVID-19相关肺曲霉病的报道引起了人们的担忧,即它使COVID-19的病程恶化并增加死亡率。此外,已报道首例由耐药唑曲霉菌引起的COVID-19相关肺曲霉菌病。本文构成了关于定义和管理COVID-19相关肺曲霉病的共识声明,由专家编写,并得到医学真菌学协会的认可。建议尽可能定义COVID-19相关的肺曲霉病,可能,或在样本有效性和诊断确定性的基础上证明。推荐的一线治疗是伏立康唑或伊沙武康唑。如果唑耐药性是一个问题,那么两性霉素B脂质体是首选药物。我们的目的是为临床研究提供定义,并为COVID-19相关肺曲霉病的诊断和治疗提供最新的临床管理建议。
    Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    2018年,世卫组织发布了诊断指南,预防,与艾滋病毒相关的隐球菌病的管理。建议采取两种策略来降低低收入和中等收入国家(LMICs)与艾滋病毒相关的隐球菌性脑膜炎相关的高死亡率:针对确诊脑膜炎病例的优化组合疗法和针对接受治疗的门诊艾滋病毒感染者的隐球菌抗原筛查计划。WHO治疗LMICs中HIV相关隐球菌性脑膜炎的首选疗法是1周的两性霉素B加氟胞嘧啶,替代疗法是氟康唑加氟胞嘧啶2周。在ACTA审判中,1周(短期)两性霉素B加氟胞嘧啶导致10周死亡率为24%(95%CI-16至32),2周氟康唑和氟胞嘧啶导致10周死亡率为35%(95%CI-29至41)。然而,与广泛使用的氟康唑单药治疗,在许多非洲LMIC环境中,HIV相关隐球菌性脑膜炎导致的死亡率约为70%.因此,在资源有限的环境中改变HIV相关隐球菌性脑膜炎的管理的潜力是巨大的.可持续获得基本药物,包括氟胞嘧啶和两性霉素B,在LMIC中是最重要的,也是这种个人观点的重点。
    In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO\'s preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-born parasitic disease characterized by various skin lesions that cause disfiguration if healed spontaneously. Although CL has been endemic for many years in the southern regions of Turkey, an increasing incidence in nonendemic regions is being observed due to returning travelers and, more recently, due to Syrian refugees. Thus far, a limited number of national guidelines have been proposed, but no common Turkish consensus has emerged.
    OBJECTIVE: The aim of this study was to develop diagnostic and therapeutic guidelines for the management of CL in Turkey.
    METHODS: This guideline is a consensus text prepared by 18 experienced CL specialists who have been working for many years in areas where the disease is endemic. The Delphi method was used to determine expert group consensus. Initially, a comprehensive list of items about CL was identified, and consensus was built from feedback provided by expert participants from the preceding rounds.
    RESULTS: Evidence-based and expert-based recommendations through diagnostic and therapeutic algorithms according to local availability and conditions are outlined.
    CONCLUSIONS: Because CL can mimic many other skin diseases, early diagnosis and early treatment are very important to prevent complications and spread of the disease. The fastest and easiest diagnostic method is the leishmanial smear. The most common treatment is the use of local or systemic pentavalent antimony compounds.
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  • 文章类型: Case Reports
    BACKGROUND: Rhinocerebral mucormycosis is a rare, rapidly progressive and potentially lethal disease almost exclusively affecting immunocompromised hosts or patients with metabolic disorders, such as poorly controlled diabetes mellitus.
    METHODS: This work is aimed to describe five cases of rhinocerebral mucormycosis to review and possibly define diagnostic and surgical treatment guidelines. In all the patients, surgical debridement, systemic and local antifungal therapy, and oral rehabilitation using filling prostheses were performed.
    RESULTS: None of the patients revealed recurrence of the infection, as confirmed by radiological and clinical long term follow up.
    CONCLUSIONS: Given the lethal nature of the disease, the authors underline the importance of early diagnosis and of a multidisciplinary approach in order to undertake correct surgical and medical treatments, while keeping the underlying disease under control.
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