Repurposing auranofin as an antifungal: In vitro activity against a variety of medically important fungi.
Wiederhold NP, Patterson TF, Srinivasan A, Chaturvedi AK, Fothergill AW, Wormley FL, Ramasubramanian AK, Lopez-Ribot JL.Virulence. 2017 Feb 17;8(2):138-142.Abstract: Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections.
Conclusion Our result demonstrate that the RLB assay potentially is suitable for rapid and simultaneous identification of variety fungal pathogens directly from culture as well as from clinical specimens.
AbstractCentral nervous system fungal infections can be broadly divided into those that infect a healthy host such asCryptococcus,Coccidioides,Histoplasma, Blastomyces,Sporothrix spp., and those that cause opportunistic infections in an immunocompromised host such asCandida,Aspergillus, Zygomycetes,Trichosporon spp. The clinical manifestations of central nervous system fungal infections commonly seen in children in clinical practice include a chronic meningitis or meningoencephalitis syndrome, brain abscess, rhino-cerebral syndrome and rarely, a fungal ventriculitis. Fungal central nervous system infections should be suspe...
Abstract The incidence of life-threatening fungal infections has dramatically increased for decades. In order to develop novel antifungal agents, two series of (2R,3R)-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(N-substitutied)-2-butanols (3a-o, 5a-f, 8a-u), which were analogues of voriconazole, were designed, synthesized and characterized by (1)H NMR, (13)C NMR and HRMS. The MIC80 values showed that the target compounds 3a-o indicated better activities than fluconazole on three important fungal pathogens except for 3i. Significant activity of compounds 3d, 3k, 3n, 3m and 3o was observed on the Aspergillus...
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.
Conclusion: The authors recommend that patients with sino-orbital fungal disease preferably be treated conservatively, without orbital exenteration.
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.
Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs penetrate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new antifungal agents: isavuconazole, ravuconazole,albaconazole and aminocandin.
Authors: Zhang PP, Xin XF, Xu XY, Fang LP, Wu J, Shi Y Abstract In recent years, along with the wide application of organ transplantation and immunosuppressive agents, as well as the abuse of broad spectrum antibiotics, the incidence of invasive fungal infections has been increasing gradually. The present study aimed to identify novel biomarkers in cells infected with Aspergillus fumigatus. Human umbilical vein endothelial cells (HUVECs) were infected with Aspergillus fumigatus and then harvested at different time-points (0, 1, 2, 4 and 6 h). The expression Toll-like receptor 2 (TLR2) and dectin-1 expression were e...
Friday, October 13, 2017 - 15:46Slide presentation
Friday, October 13, 2017 - 09:24Slide presentation