A5029698229- Antifungal resistance and susceptibility
- Pneumocystis jirovecii pneumonia detection and treatment
- Antibiotics Pharmacokinetics and Efficacy
- Fungal Infections and Studies
- Pneumonia and Respiratory Infections
- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Helminth infection and control
- Carbohydrate Chemistry and Synthesis
- Reproductive tract infections research
- Respiratory and Cough-Related Research
- Parasitic Diseases Research and Treatment
- Fungal Biology and Applications
- Microbial Natural Products and Biosynthesis
- Herbal Medicine Research Studies
- Infectious Diseases and Mycology
- Synthesis and Biological Evaluation
- Chemical synthesis and alkaloids
- Plant biochemistry and biosynthesis
- Bacterial biofilms and quorum sensing
- Bioactive Compounds and Antitumor Agents
- Breastfeeding Practices and Influences
- Bacterial Identification and Susceptibility Testing
- Nail Diseases and Treatments
- Neutropenia and Cancer Infections
Cidara Therapeutics (United States)
2016-2024
Arcturus Therapeutics (United States)
2012-2013
Merck & Co., Inc., Rahway, NJ, USA (United States)
1994-2007
United States Army Medical Research Institute of Infectious Diseases
2005
United States Military Academy
2002-2003
Virginia Commonwealth University Medical Center
1992
Pneumocandins and echinocandins are fungicidal antibiotics, currently in clinical development, that inhibit 1,3-beta-D-glucan synthase (GS) several human fungal pathogens. We have identified a gene from the diploid organism Candida albicans encodes target of these inhibitors. A 2.1-kb portion this gene, designated CaFKS1, has significant homology to Saccharomyces cerevisiae FKS1 FKS2 genes, which encode partially functionally redundant subunits GS. To evaluate role CaFkslp susceptibility...
A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories. MICs amphotericin B, fluconazole, flucytosine, ketoconazole were determined all centers against 95 coded isolates Candida spp., Cryptococcus neoformans, Torulopsis glabrata. standard protocol with the following National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Susceptibility Testing recommendations used: an inoculum standardized by...
The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated mouse models disseminated candidiasis, aspergillosis, and cryptococcosis. echinocandins are potent inhibitors 1,3-beta-D-glucan synthase. Two candidiasis were used. In a Candida albicans survival model with both DBA/2N CD-1 mice, estimates 50% effective doses (ED50s) 0.04 0.10 mg/kg body weight/dose at 21 days after challenge, respectively. C. target organ assay (TOA) levels > or...
Thirteen laboratories collaborated to optimize interlaboratory agreement of results a broth macrodilution procedure for testing three classes antifungal drugs against pathogenic yeasts. The activities amphotericin B, flucytosine, and ketoconazole were tested 100 coded isolates Candida albicans, tropicalis, parapsilosis, lusitaniae, Torulopsis (Candida) glabrata, Cryptococcus neoformans. Two starting yeast inoculum sizes (5 x 10(4) 2.5 10(3) cells per ml) compared, readings taken after 24 48...
The primary virulence factor of Bacillus anthracis is a secreted zinc-dependent metalloprotease toxin known as lethal (LF) that to the host through disruption signaling pathways, cell destruction, and circulatory shock. Inhibition this proteolytic-based LF toxemia could be expected provide therapeutic value in combination with an antibiotic during immediately after active anthrax infection. Herein shown crystal structure intimate complex between hydroxamate,...
ABSTRACT Fungal infections pose a significant public health burden with high morbidity and mortality. CD101 is novel echinocandin under development for the treatment prevention of systemic Candida infections. Preclinical studies were conducted to evaluate metabolic stability, plasma protein binding, pharmacokinetics, toxicity, efficacy at various dose levels. was stable biotransformation in rat, monkey, human liver microsomes dog, hepatocytes. In vitro suggest minimal interaction recombinant...
ABSTRACT Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority rezafungin vs caspofungin adults with and/or IC was demonstrated in Phase 3 ReSTORE study based on primary endpoints day 14 global cure 30-day all-cause mortality. Here, an analysis data evaluating efficacy outcomes by baseline Candida species described. Susceptibility testing performed using Clinical Laboratory Standards Institute...
ABSTRACT The in vivo efficacy of the echinocandin antifungal caspofungin acetate (caspofungin; MK-0991) was evaluated models disseminated aspergillosis and candidiasis mice with cyclophosphamide (CY)-induced immunosuppression. Caspofungin is a 1,3-β- d -glucan synthesis inhibitor efficacious against number clinically relevant fungi including Aspergillus Candida species. Models CY-induced transient or chronic leukopenia were used once daily administration therapy initiated 24 h after...
The pneumocandins are potent antifungal agents of the echinocandin class which under development for use as broad-spectrum antimycotic therapy. One important consideration any new therapeutic treating serious fungal infections is potential drug resistance development. In this study we have isolated and characterized four independent spontaneous Candida albicans mutants resistant to semisynthetic pneumocandin L-733,560. These many properties FKS1/ETG1 echinocandin-resistant Saccharomyces...
Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid potential MAO interactions. In vitro, were reversible inhibitors of human MAO-A MAO-B; the 50% inhibitory...
ABSTRACT Tedizolid (TR-700, formerly torezolid) is the active moiety of prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against Gram-positive species, including methicillin-resistant Staphylococcus aureus (MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg oral once daily for 5 to 7 days in patients complicated skin and structure infections. This report examines vitro activity Zyvox (linezolid) pathogens...
CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed series of studies evaluate the antifungal properties against both echinocandin-susceptible and -resistant Candida strains. Antifungal susceptibility testing on collection 95 strains 30 caspofungin-resistant isolates containing fks mutations demonstrated comparable potency relative micafungin (MCF) across different species. Comparable kinetic inhibition glucan...
Rezafungin is an investigational echinocandin under development for the treatment and prevention of invasive fungal infections, with a long half-life in humans (∼130 h) potent vitro activity against Aspergillus spp. Our objective was to further evaluate its fumigatus isolates, including azole-resistant isolates cryptic spp.Clinical were used, 15 WT 31 A. fumigatus, 11 lentulus, 5 each thermomutatus udagawae calidoustus. Minimum effective concentrations (MECs) MICs rezafungin, caspofungin,...
The in vivo anti-Candida activities of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991 (cilofungin), L-687,901 (tetrahydroechinocandin B), and L-687,781 (a papulacandin analog) were evaluated by utilizing a murine model disseminated candidiasis that has enhanced susceptibility to Candida albicans but increased sensitivity for discriminating antifungal efficacy. DBA/2 mice challenged intravenously with 1 x 10(4) 5 CFU C. MY1055 per mouse. Compounds administered intraperitoneally...
CD101 is a novel echinocandin with long half-life undergoing clinical development for treatment of candidemia/invasive candidiasis and vulvovaginal candidiasis. The potential mechanisms underlying the resistance to in Candida species were investigated by using spontaneous serial passage selection methodologies. Four spp. (C. albicans, C. glabrata, parapsilosis, krusei) chosen characterization CD101, anidulafungin, caspofungin. frequency spontaneous, single-step mutations conferring reduced...
The activities of the water-soluble pneumocandin derivatives L-733560, L-705589, and L-731373 were evaluated in mouse models disseminated aspergillosis, candidiasis, cryptococcosis compared with those commercially available antifungal agents. Pneumocandins are inhibitors 1,3-beta-D-glucan synthesis. In aspergillosis model, L-733560 L-705589 significantly prolonged survival DBA/2N mice challenged intravenously Aspergillus fumigatus conidia. exhibited efficacies comparable to that amphotericin...
Summary: Caspofungin is a new echinocandin drug with comparable in vitro activity against azole-susceptible and -resistant isolates of Candida that could provide less toxic alternative to amphotericin B for the management esophageal candidiasis clinical or laboratory evidence decreased susceptibility fluconazole. The authors retrospectively analyzed its efficacy adults endoscopically documented esophagitis from four Phase II III studies using two definitions resistance fluconazole: 1)...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, stability, and biological evaluation of water-soluble prodrugs a new echinocandin lipopeptide. Discovery potential clinical agent for the treatment systemic candidiasis Pneumocystis carinii pneumonia (PCP)James M. Balkovec, Regina Black, Milton L. Hammond, James V. Heck, Robert A. Zambias, George Abruzzo, Ken Bartizal, Helmut Kropp, Charlotte Trainor, Cite this: J. Med. Chem. 1992, 35, 1, 194–198Publication Date (Print):January...
CD101 is a novel echinocandin with concentration-dependent fungicidal activity in vitro and long half-life (∼133 h humans, ∼70 to 80 mice). Given these characteristics, it likely that the shape of exposure (i.e., time course concentrations) influences efficacy. To test this hypothesis, doses which produce same total area under concentration-time curve (AUC) were administered groups neutropenic ICR mice infected Candida albicans R303 using three different schedules. A dose 2 mg/kg was as...
The novel echinocandin CD101 has stability properties amenable to topical formulation for use in the treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). demonstrated potent antifungal activity at pH 7, but assessment its physiological vaginal environment is needed.To evaluate against clinical isolates Candida spp., including azole-resistant strains, 4.MIC values comparators (fluconazole, itraconazole, micafungin, caspofungin anidulafungin) were assessed via broth...