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Drugs in Clinical Development for Fungal Infections (includes MAT023, encochleated amphotericin B))

Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news

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Case 1: A 20-years old woman with cystic fibrosis (CF), deltaF508 homozygote, predicted 35% FEV1 was treated with inhalative antibiotics due to colonisation with Pseudomonas aeruginosa (PA). An allergic bronchopulmonary aspergillosis has previously been treated, with no evidence of reactivation. After severe exacerbations and a drop of FEV1 to 17%, she stabilized with steroids and IV-antibiotics. Despite a reduction of Pseudomonas, a low FEV1 persisted. Yeast grew in repeated sputum cultures, but could not be identified by standard methods. ITS-sequencing revealed the presence of Blastobotrys raffinosifermentans. Adequate ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Cystic Fibrosis Source Type: research
This article is protected by copyright. All rights reserved. Fungal infections that result in the death of immunocompromised subjects have risen steadily over the last few years. The metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐specific manner, has been shown to be an important virulence determinant. Characterisation of preferred nutrient source utilisation, including sensing and uptake, by pathogenic fungi has only been partially characterised, and further species‐specific elucidation is required, in order to uncover targets for anti‐fungal therapies.
Source: Molecular Microbiology - Category: Microbiology Authors: Tags: Microreview Source Type: research
SCY-078 is a novel IV/oral triterpene antifungal agent that is currently in clinical development for the treatment of invasive and mucotaneous fungal infections. It has broad-spectrum activity against both Aspergillus and Candida. Given its fungicidal activity and oral formulation a proof-of-concept study was conducted to evaluate the safety and efficacy of 2 dosing regimens of Oral SCY-078 in subjects with moderate to severe Vulvovaginal Candidiasis (VVC) and to estimate rate and time to recurrence of VVC.
Source: American Journal of Obstetrics and Gynecology - Category: OBGYN Authors: Tags: IDSOG Abstract Source Type: research
Fungal infections pose a significant public health burden with high morbidity and mortality. CD101 is a novel echinocandin under development for the treatment and prevention of systemic Candida infections. Preclinical studies were conducted to evaluate the metabolic stability, plasma protein binding, pharmacokinetics, toxicity, and efficacy of CD101 at various dose levels. CD101 was stable to biotransformation in rat/monkey/human liver microsomes and rat/monkey/dog/human hepatocytes.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
We report the case of a 53‐year‐old male with a history of acute myelogenous leukemia, who suffered the rupturing of a right‐sided pulmonary artery pseudoaneurysm combined with pneumonia. He underwent a right‐sided lower lobectomy. The resected lung tissue demonstrated a mycotic pseudoaneurysm of a pulmonary artery branch together with a filamentous fungal infection. Pseudoaneurysms are caused by the breaching of all layers of a blood vessel wall. The extravasated blood is trapped by the surrounding extravascular tissue or clots. Cladosporium was detected during a polymerase chain reaction‐based analysis followed...
Source: Pathology International - Category: Pathology Authors: Tags: Case Report Source Type: research
Most systemic fungal infections are caused by opportunistic fungal pathogens in immunocompromised hosts. However, invasive disease can occur in immunocompetent individuals if the exposure dose is high or with primary (dimorphic) fungal pathogens (causes of endemic mycoses include Blastomyces, Coccidioides, Histoplasma, Paracoccidioides and Talaromyces spp.). Systemic fungal infections usually originate either in the lungs (Aspergillus, Cryptococcus, Mucorales spp., as a result of inhalation) or from endogenous flora (Candida spp.
Source: Medicine - Category: Internal Medicine Authors: Tags: Fungal infections Source Type: research
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Abstract BackgroundProspective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. MethodsNIH‐sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post‐transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI‐related risks and outcomes. ResultsIn 59 PLT, pre‐transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre‐...
Source: Clinical Transplantation - Category: Transplant Surgery Authors: Tags: Original Article Source Type: research
C Agrawal, V Sood, A Kumar, V RaghavanIndian Journal of Nephrology 2017 27(5):392-394 Invasive fungal infections (IFIs) are a significant cause of morbidity in solid organ transplant (SOT) recipients. Common causes among them are Aspergillus, Candida, and Cryptococcus. Antifungal prophylaxis has led to decrease in overall incidence of IFI; however, there is very little decline in the incidence of Cryptococcal infections of SOT recipients because effective prophylaxis is not available against this infectious agent. Spectrum of manifestation of Cryptococcal infection varies in immunocompetent and immunocompromised host with...
Source: Indian Journal of Nephrology - Category: Urology & Nephrology Authors: Source Type: research
All serious fungal infections need appropriate antifungal therapy for successful patient outcome. Only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. Azole resistance among Candida and Aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida species, especially Candida glabrata. The spread of agriculturally derived azole-resistant Aspergillus fumigatus and emerging threats such as multidrug resistant Candida auris are also alarming.
Source: The Lancet Infectious Diseases - Category: Infectious Diseases Authors: Tags: Series Source Type: research
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