Preclinical Evaluation of the Stability, Safety and Efficacy of CD101, a Novel Echinocandin

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

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AbstractAutosomal recessive CARD9 deficiency underlies life-threatening, invasive fungal infections in otherwise healthy individuals normally resistant to other infectious agents. In less than 10  years, 58 patients from 39 kindreds have been reported in 14 countries from four continents. The patients are homozygous (n = 49; 31 kindreds) or compound heterozygous (n = 9; 8 kindreds) for 22 differentCARD9 mutations. Six mutations are recurrent, probably due to founder effects. Paradoxically, none of the mutant alleles has been experimentally demonstrated to be loss-of-function. CARD9 is expre...
Source: Journal of Clinical Immunology - Category: Allergy & Immunology Source Type: research
We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients’ neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely u...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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
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