Amphotericin B

两性霉素 B
  • 文章类型: Case Reports
    肺毛霉菌病在肾移植受者中很少见,死亡率很高。我们报告了一例移植后1年和1个月表现为圆形肺炎的肺毛霉菌病。通过经皮肺活检证实了诊断。完全切除肺肿块,然后静脉注射脂质体两性霉素B治疗,挽救了病人的生命。总之,早期和及时诊断,然后完全切除肺毛霉菌病的病灶可以挽救生命。
    Pulmonary mucormycosis is rare in kidney transplant recipients and has a high mortality rate. We report a case of pulmonary mucormycosis presenting as round pneumonia 1 year and 1 month after the transplant. The diagnosis was confirmed by a percutaneous lung biopsy. A complete resection of the lung mass, followed by intravenous liposomal amphotericin B therapy, saved the life of the patient. In conclusion, early and prompt diagnosis followed by complete resection of the lesion in pulmonary mucormycosis is lifesaving.
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  • 文章类型: Case Reports
    背景:犀牛-眶-脑毛霉菌病(ROCM)是一种罕见的,机会主义,血管侵入性,以及根霉属霉菌引起的致命感染,Mucor,和根佐科。ROCM的全球发病率为百万分之0.005-1.7,死亡率为46%。早期诊断和治疗对这种疾病至关重要,延迟一周可以将死亡率提高到66%。
    方法:一名32岁男性,Janakpur过去15天已知的2019年冠状病毒病(COVID-19)病例,Dhanusha,尼泊尔向Dhulikhel医院急诊科就诊,左眼突然出现视力模糊,左侧眼痛,还有最近三天的鼻出血.
    方法:患者被怀疑患有COVID-19后毛霉菌病,和氢氧化钾(KOH)安装的鼻拭子在显微镜下显示菌丝。静脉和球后脂质体两性霉素B作为药物治疗给药,以及手术清创。治疗需要多学科方法。
    结论:长期,多模式治疗方法包括联合抗真菌药物治疗(静脉注射脂质体两性霉素B和球后两性霉素B),及时的手术清创可改善短期和长期结局.
    BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare, opportunistic, angio-invasive, and fatal infection caused by mold fungi of the genera Rhizopus, Mucor, and Rhizomucor. The global incidence of ROCM is 0.005-1.7 per million, with a fatality rate of 46%. Early diagnosis and treatment are crucial for this disease, as a delay of one week can increase the mortality rate to 66%.
    METHODS: A 32-year-old male, a known case of coronavirus disease 2019 (COVID-19) for the past 15 days from Janakpur, Dhanusha, Nepal presented to the emergency department of Dhulikhel Hospital with a sudden onset of blurred vision in the left eye, left-sided ocular pain, and nasal bleeding for the last three days.
    METHODS: The patient was suspected of post-COVID-19 mucormycosis, and a nasal swab for potassium hydroxide (KOH) mount showed hyphae in microscopy. Intravenous and retrobulbar liposomal amphotericin B were administered as medical therapy, along with surgical debridement. A multidisciplinary approach was necessary for the treatment.
    CONCLUSIONS: A long-term, multimodal treatment approach involving combined antifungal drug therapy (intravenous liposomal amphotericin B and retrobulbar amphotericin B), and timely surgical debridement leads to an improvement in both short-term and long-term outcomes.
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  • 文章类型: Journal Article
    新生隐球菌在“最想要的”人类病原体列表中名列前茅。只有三类抗真菌药物可用于治疗隐球菌病。抗真菌耐药机制的研究仅限于研究特定抗真菌药物如何诱导对特定药物的耐药性,除抗真菌药以外的胁迫对抗真菌抗性甚至交叉抗性的发展的影响在很大程度上尚未被探索。内质网(ER)是真核细胞中普遍存在的亚细胞器。BrefeldinA(BFA)是一种广泛使用的ER应激化学诱导剂。这里,我们发现,BFA的弱选择和强选择都会导致新生梭菌的非整倍性形成,主要是1号染色体、3号染色体和7号染色体的二体性。染色体1的二分体赋予了对两类抗真菌药物的交叉抗性:氟康唑和5-氟胞嘧啶,以及对两性霉素B的超敏反应。耐药性不稳定,由于非整倍体的内在不稳定性。我们发现染色体二分体赋予的Chr1和Chr3表型复制的BFA抗性上的AFR1过表达。AFR1的过表达也导致对氟康唑的耐药性和对两性霉素B的超敏反应。AFR1缺失的菌株在BFA处理后未能形成1号染色体二体性。转录组分析表明,1号染色体二体性同时上调AFR1,ERG11和其他外排和ERG基因。因此,我们认为BFA有可能推动新型梭菌耐药性甚至交叉耐药性的快速发展,以基因组可塑性为帮凶。
    Cryptococcus neoformans is at the top of the list of \"most wanted\" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.
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  • 文章类型: Case Reports
    原发性皮肤毛霉菌病是由环境真菌引起的,即使在有免疫能力的个体中,也可能使腿部溃疡或外伤复杂化。该病例报告重点介绍了2型糖尿病患者的复发性下肢溃疡和蜂窝织炎,对常规抗生素治疗无反应。组织病理学诊断为皮肤毛霉菌病,真菌培养物鉴定出变异根霉为致病生物。最初的口服唑类抗真菌剂仅产生部分反应,他最终需要静脉内治疗。两性霉素B和口服泊沙康唑。这种情况的良好治疗结果需要高度的临床怀疑,早期组织病理学和微生物学诊断,有针对性的全身抗真菌治疗,必要时进行手术清创。
    Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary.
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  • 文章类型: Journal Article
    念珠菌是最常见的真菌感染之一,与高发病率和死亡率相关。喹喔啉衍生物是一组显示有希望的抗微生物活性的小分子。本研究以两性霉素B为对照,探讨3-肼基喹喔啉-2-硫醇对念珠菌的杀菌效果。此外,我们旨在使用小鼠口腔念珠菌病模型评估3-肼基喹喔啉-2-硫醇的体内疗效。通过肉汤微量稀释法对56株念珠菌分离株进行了3-肼基喹喔啉-2-硫醇和两性霉素B的药敏试验。因此,评估和比较最小抑制浓度(MIC)。口腔念珠菌病小鼠模型用于评估3-肼基喹喔啉-2-硫醇的体内活性。本研究使用进展的微生物学评估和ELISA。3-肼基喹喔啉-2-硫醇对大多数白色念珠菌临床分离株比两性霉素B更有效。对光滑念珠菌和近针型念珠菌分离株的有效性更高。然而,对热带念珠菌分离株的效率各不相同。3-肼基喹喔啉-2-硫醇对库德里亚夫泽维毕赤酵母和lusitaniae也有效。3-肼基喹喔啉-2-硫醇在小鼠模型中显示针对白色念珠菌细胞ATCC10231的良好功效。3-肼基喹喔啉-2-硫醇对不同的念珠菌物种显示出有希望的抗真菌和抗炎活性。需要更多的测试和实验。
    Candida ranks as among the most frequently encountered fungal infections that associated with high morbidity and mortality. Quinoxaline derivatives are a group of small molecules that showed a promising antimicrobial activity. This study aimed to investigate the fungicidal effects of 3-hydrazinoquinoxaline-2-thiol against Candida in comparison with Amphotericin B in vitro as a reference. Also, we aim to assess the efficacy of 3-hydrazinoquinoxaline-2-thiol in vivo using mice oral candidiasis model. Fifty-six Candida isolates were subjected to susceptibility testing by broth microdilution method for 3-hydrazinoquinoxaline-2-thiol and Amphotericin B. Therefore, Minimal inhibitory concentrations (MIC) were assessed and compared. The oral candidiasis mice model was used to evaluate the activity of 3-hydrazinoquinoxaline-2-thiol in vivo. Microbiological evaluation of progression and ELISA were used in this study. 3-hydrazinoquinoxaline-2-thiol was more effective than Amphotericin B against most clinical isolates of Candida albicans. Higher effectiveness was seen against Candida glabrata and Candida parapsilosis isolates. However, the efficiency against Candida tropicalis isolates varies. 3-hydrazinoquinoxaline-2-thiol was also effective against Pichia kudriavzevii and Clavispora lusitaniae. 3-hydrazinoquinoxaline-2-thiol showed a good efficacy in mice model against C. albicans cells ATCC 10231. 3-hydrazinoquinoxaline-2-thiol has shown promising antifungal and anti-inflammatory activity against different Candida species. More tests and experiments are needed.
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  • 文章类型: Case Reports
    一名61岁的女性,患有糖尿病和5期慢性肾脏疾病,自3年以来通过左头臂动静脉瘘进行血液透析,糖分不受控制,减肥,和吞咽困难.关于评估,她被发现患有鹅口疮并伴有白细胞增多症。最初的血液和尿液培养是无菌的,超声检查显示肝脏左叶有低回声病变。她在入院后第10天高烧,随后癫痫发作。脑影像学和血清电解质正常。脑脊液分析是非贡献性的,尿液培养显示非白色念珠菌白细胞计数升高。她开始服用氟康唑;然而,她的临床状况恶化了,血液动力学不稳定。重复腹部计算机断层扫描显示,肝脏左叶低密度病变增加,βD葡聚糖水平升高。脓肿的经皮引流没有发现真菌成分。鉴于临床恶化,两性霉素B开始,导致临床改善。临床医师应高度怀疑存在肝脓肿的血液透析患者的真菌病因。
    A 61-year-old female with diabetes and stage 5 chronic kidney disease on hemodialysis since 3 years via left brachiocephalic arteriovenous fistula presented with uncontrolled sugars, weight loss, and dysphagia. On evaluation, she was found to have an oral thrush with leucocytosis. Initial blood and urine cultures were sterile, and ultrasonography revealed hypoechoic lesions in the left lobe of the liver. She had high-grade fever followed by seizures on postadmission Day 10. Brain imaging and serum electrolytes were normal. Cerebrospinal fluid analysis was noncontributory, and urine culture revealed Candida non-albicans with elevated white blood cell counts. She was started on fluconazole; however, her clinical condition deteriorated, with hemodynamic instability. Repeat abdominal computerized tomography revealed increasing hypodense lesions in the left lobe of the liver with elevated beta D glucan levels. Percutaneous drainage of the abscess revealed no fungal elements. In view of clinical deterioration, amphotericin B was started, which resulted in clinical improvement. Clinician should have high index of suspicion for fungal etiology in hemodialysis patients presenting with liver abscess.
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  • 文章类型: Case Reports
    皮肤科假单胞菌瘤(DPM),这是皮肤癣菌的更深的皮肤和/或皮下感染,在韩国国内的短毛猫中很少有报道。一个三岁的孩子,Spyed女性,国内韩国短毛猫提出了一个历史的硬皮,结节,瘙痒1年。在最初的演讲中,在她的腹侧胸腔上发现了覆盖着淡黄色颗粒的多灶性溃疡性结节,腹部,侧翼,和左后肢。溃疡性结节的细胞学显示中性粒细胞变性,巨噬细胞,多核巨细胞,和菌丝。结节的组织学检查显示脓性肉芽肿性皮炎伴真菌斑块,在培养物中鉴定出犬小孢子菌和金黄色葡萄球菌。因此,这只猫被诊断为患有继发性脓皮病的DPM。口服伊曲康唑(10mg/kg,一天一次)被施用,但没有观察到显著的改善。因此,损伤内(IL)注射两性霉素B(0.6mg/结节)和口服特比萘芬(30mg/kg,一天两次)给猫服用。有了这些药物,溃疡和结节的数量和大小显着减少,虽然大的圆顶状结节仍然存在。皮肤病变采用口服特比萘芬和伊曲康唑治疗5个月。然而,6个月后,观察到多灶性溃疡性结节复发,猫在初次陈述后10个月死亡。在这种情况下,IL两性霉素B和口服特比萘芬在DPM治疗中部分有效,这表明这可能是DPM治疗的一种选择。有必要进一步研究以确定IL两性霉素B在DPM管理中的剂量和频率。
    Dermatophytic pseudomycetoma (DPM), which is a deeper dermal and/or subcutaneous infection of dermatophytes, has been rarely reported in Domestic Korean Short Hair Cats. A 3-year-old, spayed female, domestic Korean Short Hair Cat presented with a history of crusts, nodules, and pruritus for 1 year. At the initial presentation, multifocal ulcerative nodules covered with yellowish grains were noted on her ventral thorax, abdomen, flank, and left hindlimb. Cytology of ulcerative nodules revealed degenerative neutrophils, macrophages, multinucleated giant cells, and hyphae. Histological examination of nodules revealed pyogranulomatous dermatitis with fungal plaques, and Microsporum canis and Staphylococcus aureus were identified in the culture. Therefore, the cat was diagnosed with DPM with secondary pyoderma. Oral itraconazole (10 mg/kg, once a day) was administered, but no significant improvement was observed. Therefore, intralesional (IL) injection of amphotericin B (0.6 mg/nodule) and oral administration of terbinafine (30 mg/kg, twice a day) were administered to the cat. With these medications, ulceration and the number and size of nodules decreased significantly, although large dome-shaped nodules remained. Skin lesions were treated with oral terbinafine and itraconazole administration for 5 months. However, after 6 months, recurrence of multifocal ulcerative nodules was observed, and the cat died 10 months after initial presentation. In this case, IL amphotericin B and oral terbinafine administration were partially effective in DPM treatment, suggesting that this may be an option for DPM treatment. Further studies to determine dose and frequency of IL amphotericin B in the management of DPM are warranted.
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  • 文章类型: Case Reports
    肺毛霉菌病(PM)是一种侵袭性和潜在致命的真菌感染,与小根霉(R.微孢子菌)是最常见的病原体。这种感染的常规治疗包括手术和抗真菌药物。然而,由于毛霉菌病的快速进展,单一药物的治疗效果不令人满意,虽然并非所有患者都能耐受手术。创新的治疗方法,如联合治疗,等待其临床疗效的验证。我们报告了一例PM,通过宏基因组学对患者肺部黑色引流液的下一代测序(mNGS)诊断。患者最终康复,并在口服伊沙武康唑联合治疗后出院,吸入两性霉素B,并通过支气管镜局部灌注两性霉素B,这可能是治疗PM的一个有希望的策略,尤其是在无法进行手术的情况下。通过对297例文献的回顾性研究,强调了临床实践中使用的不同治疗方法。
    Pulmonary mucormycosis (PM) is an invasive and potentially fatal fungal infection, with Rhizopus microsporus (R. microsporus) being the most common pathogen. The routine therapy for this infection includes surgery and antifungal agents. However, the therapeutic effects of single agents are unsatisfactory due to the rapid progression of mucormycosis, while not all patients can tolerate surgery. Innovative treatment methods like combination therapy await validations of their clinical efficacy. We report a case of PM that was diagnosed via metagenomics next-generation sequencing (mNGS) of black drainage fluid from the patient\'s lung. The patient eventually recovered and was discharged after a combination therapy of oral isavuconazole, inhaled amphotericin B, and local perfusion of amphotericin B through bronchoscopy, which may be a promising strategy for the treatment of PM, especially for cases where surgery is not possible. A retrospective study of 297 cases in a literature review highlights the different treatment methods used in clinical practice.
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  • 文章类型: Journal Article
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