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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ConclusionsWe conclude that micafungin was clinically effective for the treatment of invasive candida and aspergillus infections and that usage did not increase the risk of liver dysfunction even in patients with abnormal ALT at baseline.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
C. Teixeira Fungal infections caused by Candida, Aspergillus, and Cryptococcus species are an increasing problem worldwide, associated with very high mortality rates. The successful prevalence of these human pathogens is due to their ability to thrive in stressful host niche colonization sites, to tolerate host immune system-induced stress, and to resist antifungal drugs. This review focuses on the key role played by multidrug resistance (MDR) transporters, belonging to the ATP-binding cassette (ABC), and the major facilitator superfamilies (MFS), in mediating fungal resistance to pathogenesis-related stresses. These ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
Conclusions We conclude that micafungin was clinically effective for the treatment of invasive candida and aspergillus infections and that usage did not increase the risk of liver dysfunction even in patients with abnormal ALT at baseline.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
lliam N. Setzer There is an urgent and unmet need for new antifungal therapies. Global fungal infection rates continue to rise and fungal infections pose increasing burdens on global healthcare systems. Exacerbating the situation, the available antifungal therapeutic arsenal is limited and development of new antifungals has been slow. Current antifungals are known for unwanted side effects including nephrotoxicity and hepatotoxicity. Thus, the need for new antifungals and new antifungal targets is urgent and growing. A collection of 60 commercially-available essential oils has been screened for antifungal activity agai...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Abstract Rhizopus oryzae is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work is to establish if the Rhizopus oryzae CYP51 genes are the unique responsible for voriconazole and fluconazole intrinsic resistance in these fungal pathogens. Two CYP51 genes were identified...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
ConclusionAlthough the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
Source: Infection - Category: Infectious Diseases Source Type: research
Abstract Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
Abstract SCY-078, the first in a new class of β 1,3-glucan synthesis inhibitors, is being developed as an oral and intravenous antifungal treatment for Candida and Aspergillus species fungal infections. In vitro, studies indicated SCY-078 is an inhibitor of cytochrome P450 (CYP) 2C8 with markedly lower effect over other CYP isozymes. To examine clinically relevant effects of the potential interaction with SCY-078, this phase 1, open-label, 2-period crossover study evaluated the pharmacokinetic parameters of rosiglitazone, a sensitive substrate of CYP2C8 metabolism, in the absence and presence of SCY-078 dosed...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research
AbstractChronic suppurative otitis media (CSOM) has a substantial worldwide prevalence and is a major cause of hearing impairment. In cases of CSOM unresponsive to local antibiotics, superimposed fungal infection should be suspected. The aim of the present study was to study the spectrum of cases with fungal otitis media. The study was conducted over a period of 12  years (2006–2017). Fifteen cases of CSOM clinically not suspected to be of fungal etiology that underwent surgery with identification of fungal organisms on histopathology were included in the study. Age of the patients ranged from 12 to 75 year...
Source: Head and Neck Pathology - Category: Pathology Source Type: research
u-Tsodikova As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
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