Candida
SusceptibilityEUCAST Reference Testing of Rezafungin Susceptibility and Impact of Choice of Plastic PlatesRezafungin is a new long-acting echinocandin currently in phase 3 development. Epidemiological cutoff values are necessary for breakpoint setting but have not been established due to unexplained interlaboratory MIC variations observed in a prior multicenter study. Here we investigated if the choice of microtiter plates affected the variability when anidulafungin was included as a comparator.
SusceptibilityFluconazole Resistance in Isolates of Uncommon Pathogenic Yeast Species from the United KingdomThe triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with...
Clinical TherapeuticsPopulation Pharmacokinetics of Anidulafungin in Critically Ill PatientsA two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model.
SusceptibilityEUCAST Susceptibility Testing of Isavuconazole: MIC Data for Contemporary Clinical Mold and Yeast IsolatesIsavuconazole is the newest medical azole. We investigated EUCAST MICs for isavuconazole and seven comparators against 1,498 contemporary isolates (2016 to 2017).
Mechanisms of ResistanceA Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida SpeciesThe increasing incidence of and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern.
Mechanisms of ResistanceAbrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida aurisCandida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida...
Mechanisms of ResistanceComparative Genomics of Serial Candida glabrata Isolates and the Rapid Acquisition of Echinocandin Resistance during TherapyThe opportunistic pathogen Candida glabrata shows a concerning increase in drug resistance. Here, we present the analysis of two serial bloodstream isolates, obtained 12 days apart.
SusceptibilityAPX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference MethodAPX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one used the EUCAST method.
Experimental TherapeuticsSignificantly Improved Pharmacokinetics Enhances In Vivo Efficacy of APX001 against Echinocandin- and Multidrug-Resistant Candida Isolates in a Mouse Model of Invasive CandidiasisAPX001 is a first-in-class, intravenous and orally available, broad-spectrum antifungal agent in clinical development for the treatment of life-threatening invasive fungal infections. The half-life of APX001A, the active moiety of APX001, is significantly shorter in mice than in humans (1.4 to 2.75 h in mice versus 2 to 2.5 days in humans), making the exploration of efficacy in mouse models difficult.
- Clinical TherapeuticsEchinocandin Treatment of Candida albicans Biofilms Enhances Neutrophil Extracellular Trap Formation
The nosocomial pathogen Candida albicans forms biofilms on medical devices that persist in the face of antifungals and host defenses. Echinocandins, the most effective antibiofilm drugs, have recently been shown to augment the activity of neutrophils against biofilms through an unknown mechanism.