Candida
Experimental TherapeuticsFormulation, Pharmacological Evaluation, and Efficacy Studies of Occidiofungin, a Novel AntifungalOccidiofungin is a nonribosomally synthesized cyclic lipopeptide that possesses broad-spectrum antifungal properties at submicromolar concentrations. This report explores multiple routes of administration and formulations of occidiofungin, as well as its toxicity in mice. Further, infection studies were performed in mice to assess the application of occidiofungin for treating systemic and intravaginal yeast infections. Formulations for...
SusceptibilityEvaluation of Two Commercial Broth Microdilution Methods Using Different Interpretive Criteria for the Detection of Molecular Mechanisms of Acquired Azole and Echinocandin Resistance in Four Common Candida SpeciesThe abilities of the new Vitek 2 AST-YS08 (YS08) and Sensititre YeastOne (SYO) systems to detect the resistances of Candida isolates to azoles and echinocandins were evaluated. In total, 292 isolates, including 28 Candida albicans (6 Erg11 and 2 Fks mutants), 57 Candida parapsilosis (26...
Chemistry; BiosynthesisLactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin BLactoferrin (LF) is an iron-binding glycoprotein with broad-spectrum antimicrobial activity. Previously, we discovered that LF synergistically enhanced the antifungal efficacy of amphotericin B (AMB) across a variety of yeast species and subsequently hypothesized that this synergy was enhanced by the presence of small peptides derived from the whole LF molecule. In this study, LF was digested with pepsin under a range of conditions. The...
Mechanisms of ResistanceFirst Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in TurkeyClonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR C. parapsilosis blood isolates have not been reported in...
Mechanisms of ResistanceCombination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.The occurrence and recurrence of mucosal biofilm-related Candida infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused by Candida spp., for example, affect 70 to 75% of women at least once during their lives. Miconazole (MCZ) is the preferred topical treatment against these fungal infections, yet it has only moderate antibiofilm activity. Through screening of a...
Epidemiology and SurveillanceAntifungal Susceptibility of Clinical Yeast Isolates from a Large Canadian Reference Laboratory and Application of Whole-Genome Sequence Analysis To Elucidate Mechanisms of Acquired ResistanceTo understand the epidemiology and susceptibility patterns of yeast infections in Ontario, Canada, we examined 4,715 clinical yeast isolates submitted to our laboratory for antifungal susceptibility testing from 2014 to 2018. Candida albicans was the most frequently submitted species (43.0%), followed by C...
Experimental TherapeuticsPreclinical Evaluation of Acylhydrazone SB-AF-1002 as a Novel Broad-Spectrum Antifungal AgentThe incidence of invasive fungal infections is rising due to the increase in susceptible populations. Current clinically available drugs have therapeutic limitations due to toxicity, a narrow spectrum of activity, and, more importantly, the consistent rise of fungal species that are intrinsically resistant or that develop resistance due to prolonged therapy. Thus, there is an urgent need for new broad-spectrum antifungal agents with low...
Mechanisms of Action: Physiological EffectsChemokine CCL28 Is a Potent Therapeutic Agent for Oropharyngeal CandidiasisCandida albicans is a commensal organism that causes life-threatening or life-altering opportunistic infections. Treatment of Candida infections is limited by the paucity of antifungal drug classes. Naturally occurring antimicrobial peptides are promising agents for drug development. CCL28 is a CC chemokine that is abundant in saliva and has in vitro...
SusceptibilityLactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin BLactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertook a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mold...
